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  • Undergraduate Poster Abstracts
  • Neuroscience

    THU-766 MEC-DEPENDENT MEMORY FORMATION: A CLOSER LOOK INTO THE MEMORY CIRCUITRY

    • Naznin Jahan ;
    • Jena Hales ;
    • Robert Clark ;

    THU-766

    MEC-DEPENDENT MEMORY FORMATION: A CLOSER LOOK INTO THE MEMORY CIRCUITRY

    Naznin Jahan1, Jena Hales2, Robert Clark2.

    1University of California, Berkeley, Berkeley, CA, 2University of California, San Diego, La Jolla, CA.

    The medial temporal lobe of the brain consists of medial entorhinal cortex (MEC)-hippocampal circuitry, known to be important for memory formation and retrieval. Our lab has previously shown that MEC lesions caused partial deterioration of some hippocampal-dependent spatial encoding, specifically watermaze acquisition, but not others including context fear memory acquisition. These findings suggest that MEC and hippocampus are involved in different types of memory formation. Using rats as our model organism, we did bilateral excitotoxic lesions of the MEC in the experimental group and sham surgeries in the control group. After a 2-week recovery period, both groups underwent trace fear conditioning. Rats were then tested on their memory for the context and tone that were predictive of the shocks during training. Percent freezing was measured as an index of fear memory. Our preliminary findings suggest that rats with MEC lesions show intact freezing to the context, but deficits in trace fear memory. These findings suggest that there might be an involvement of MEC in trace fear acquisition and timing of memory formation.

    THU-846 INDUCTION OF DFOSB FOLLOWING PHYSICAL AND EMOTIONAL STRESS

    • Darlyn Caraballo ;
    • Megan Kechner ;
    • Michelle Mazei ;

    THU-846

    INDUCTION OF DFOSB FOLLOWING PHYSICAL AND EMOTIONAL STRESS

    Darlyn Caraballo1, Megan Kechner2, Michelle Mazei2.

    1University of Puerto Rico, Arecibo, PR, 2Michigan State University, East Lansing, MI.

    Depression is a devastating disease, and the underlying cellular mechanisms are not well understood. To study this, we have employed physical (PS) and emotional (ES) chronic social defeat stress as mouse models of depression. In ES, mice do not receive any physical stress, but witness physical subordination of another mouse. ES has been shown to produce many of the same depressive-like behaviors as PS. Exposure to PS has been shown to promote differences in DFosB induction in multiple brain regions including the nucleus accumbens (NAc), a region known to play a significant role in motivation, pleasure, and reward. With this in mind, we sought to investigate if the induction of DFosB was similar between PS and ES. Eight-week-old c57BL/6J male mice were exposed to either PS or ES for 5 minutes per day for 10 days. PS mice were placed into the home cage of a CD-1 aggressor mouse, and ES mice were placed into the same cage but were physically separated from the CD-1 and PS mouse by a perforated plexiglas partition. One-hour following social interaction testing on day 11, mice were perfused and brains were post-fixed and cryoprotected. Brains were then sectioned, and immunohistochemistry was performed for ΔFosB. FosB-positive cells were counted in multiple brain regions including NAc, dorsal and ventral hippocampus, prefrontal cortex and ventral tegmental area to assess whether PS and ES induce a similar pattern of induction. This work could identify brain regions important for depressive behaviors on which to focus in future studies.

    THU-767 UNDERSTANDING HOW SEX MODULATES THE FEMALE NERVOUS SYSTEM TO DRIVE DISTINCT REPRODUCTIVE BEHAVIOR STATES

    • Layla Nassar ;
    • Addys Bode ;
    • Kevin Collins ;

    THU-767

    UNDERSTANDING HOW SEX MODULATES THE FEMALE NERVOUS SYSTEM TO DRIVE DISTINCT REPRODUCTIVE BEHAVIOR STATES

    Layla Nassar, Addys Bode, Kevin Collins.

    University of Miami, Coral Gables, FL.

    We are interested in understanding how mating and reproductive behaviors are coordinated in the female nervous system. Specifically, we are identifying the neural signaling systems that drive two mutually exclusive C. elegans vulval motor behaviors: mating with males or the release of progeny during egg laying. We hypothesize that 1) female vulval muscle twitching contractions facilitate male spicule insertion during mating, 2) specific mechanical and chemical signals report successful copulation and insemination, and 3) mating initiates reproductive behaviors including oocyte production and egg release. To investigate these hypotheses, we are using calcium imaging techniques to record vulval signaling events during mating with males, after successful insemination, and during the resumption of normal egg laying behavior. We have found that hermaphrodites with sperm have reduced vulval muscle twitching behaviors resulting in inefficient mating. In contrast, hermaphrodites depleted of sperm have increased vulval muscle twitching that facilitates male spicule insertion and mating. After mating is complete, hermaphrodites display distinct and sustained vulval muscle contractions. Sharp vulval muscle contractions during mating have been shown to result in release of sperm from the uterus. This behavior may act as a mechanism for competition with self-sperm. We are now examining how the other cells in the egg-laying circuit, including the HSN and VC neurons and uv1 neuroendocrine cells, respond during steps of male mating. Together, these results will explain how internal and external signals modulate activity in the same neural circuit to drive distinct behavior states.

    FRI-844 INVESTIGATION OF HIPPOCAMPAL PATHWAYS IN A MOUSE MODEL OF LEAD EXPOSURE RELEVANT TO THE EL PASO REGION

    • Luis Martinettis ;
    • Karine Fénelon ;

    FRI-844

    INVESTIGATION OF HIPPOCAMPAL PATHWAYS IN A MOUSE MODEL OF LEAD EXPOSURE RELEVANT TO THE EL PASO REGION

    Luis Martinettis, Karine Fénelon.

    The University of Texas at El Paso, El Paso, TX.

    Children in low income neighborhoods found throughout the U.S. and the El Paso-Ciudad Juarez border region are exposed early in life to low lead (Pb) levels and show learning and memory impairments. This project aims to determine the effects of low-levels of Pb exposure on the neuronal activity of the hippocampus. Previous studies reported that high levels of Pb exposure alter hippocampal functions. The mechanisms by which low-levels of Pb affects neuronal function are still ill defined. This study compared adult mice not exposed to Pb (control) to adult mice exposed to high Pb levels (330 ppm) or low Pb levels (30 ppm) from birth to post-natal day 28. The 30 ppm exposure was used because it yielded blood Pb levels matching those observed in children of El Paso. Using both types of exposed mice, extracellular field recordings were performed in the CA1 region of acute hippocampal slices as well as optogenetics experiments in acute slices to determine alterations in hippocampus-PFC synapses. Our results revealed synaptic transmission and short-term synaptic depression abnormalities in both low (n = 9) and high (n = 9) Pb-level-exposed mice compared to control mice (n = 17), and suggest synaptic strength and short-term synaptic depression are also altered by both high (n = 3) and low Pb (n = 2) levels at hippocampus-PFC synapses. Overall, these results contribute to better understand the effects of low-level Pb exposure on learning and memory in children exposed early in life to low Pb levels.

    FRI-851 AGING AND THE BLOOD-BRAIN BARRIER: WHAT THE ALBUMIN AND TGF-β RECEPTOR REVEAL ABOUT THE ONSET OF COGNITIVE DECLINE

    • Helen Harrison ;
    • Aaron Friedman ;
    • Daniela Kaufer ;
    • Vladimir Senatorov ;

    FRI-851

    AGING AND THE BLOOD-BRAIN BARRIER: WHAT THE ALBUMIN AND TGF-β RECEPTOR REVEAL ABOUT THE ONSET OF COGNITIVE DECLINE

    Helen Harrison1, Aaron Friedman1, Daniela Kaufer2, Vladimir Senatorov2.

    1University of California, Berkeley, Berkeley, CA, 2Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.

    Age-related breakdown of the blood-brain barrier (BBB) has been associated with the development of epilepsy, Alzheimer’s disease, and cognitive decline. This has major implications for the health of the aging population and may explain the onset of such neurodegenerative disorders in the elderly. Characterization of this type of neurodegeneration is key to early detection and pharmacological intervention. Our research suggests that BBB breakdown triggers a cascade of pathology initiated by the blood protein albumin, which binds to the transforming growth factor-β receptor (TGF-βR) on astrocytes. Activation of this receptor initiates a pro-inflammatory pathway that leads to a pathogenic disruption in normal neuronal activity. To investigate the role of this mechanism in contributing to cognitive decline, we injected aged mice (24 months old, near the end of the mouse lifespan) with IPW, a drug that blocks activation of the TGF-β receptor, and then tested memory function using the novel object task in which mice have to recognize a novel object among a set of previously viewed (familiar) objects. We found that aged mice given IPW had better memory performance compared to controls, suggesting that blocking albumin signaling can reduce cognitive decline. To test the direct effects of albumin, we also performed stereotaxic surgery to implant osmotic minipumps that deliver albumin directly into the brain of young mice, which do not otherwise have impaired BBB. We then tested whether albumin-induced pathology directly caused impairments in novel object memory and whether IPW can prevent these declines.

    THU-782 GLASS PATTERN RESPONSES AND CHOICE-RELATED ACTIVITY IN MACAQUE V4 NEURONS

    • Eden Sayed ;
    • Michele Basso ;

    THU-782

    GLASS PATTERN RESPONSES AND CHOICE-RELATED ACTIVITY IN MACAQUE V4 NEURONS

    Eden Sayed, Michele Basso.

    University of California, Los Angeles, Los Angeles, CA.

    Studies on perceptual decision making reveal that various areas in the parietal cortex, particularly the lateral intraparietal area (LIP) and the parietal reach region, are involved in decision making. These studies, however, predominantly used tasks that only probe the spatial and motion-based visual processing in the brain, known to be implemented in the dorsal stream of the visual system. It is an open question where in the ventral stream, the stream responsible for form-based processing, decisions are computed. Visual area V4 in macaques is a midlevel area in the ventral stream and is believed to be responsible for processing form-based information. We hypothesized that choice-related activity in the ventral stream would be detected in V4. To test this hypothesis, macaques were presented with Glass pattern, a form-based stimulus, of 2 different orientations. Trained macaques indicated whether the Glass pattern was oriented to the right or to the left by making an eye movement. We plan to monitor single neurons in V4 as the macaques perform this decision-making task. We predict that neurons in area V4 will show differential activity to Glass patterns of different orientations, consistent with their known orientation selectivity as measured with Gabor stimuli. We also predict that V4 neurons will show activity correlated with perceptual choices made by monkeys as quantified using signal detection theoretic tools. If choice-related neuronal activity is found in area V4 of monkeys performing this decision task, we will conclude that form-based perceptual decisions involve the circuits of the ventral visual stream.

    THU-855 AN ANATOMICAL AND FUNCTIONAL ANALYSIS OF CORTICOSTRIATAL PROJECTION AND CORTICOSPINAL COLLATERALS

    • Christian Hissom ;
    • James Conner ;

    THU-855

    AN ANATOMICAL AND FUNCTIONAL ANALYSIS OF CORTICOSTRIATAL PROJECTION AND CORTICOSPINAL COLLATERALS

    Christian Hissom, James Conner.

    University of California, San Diego, San Diego, CA.

    Corticostriatal projections (CStr) and corticospinal collaterals (CStc) are integral to motor control. It’s widely projected that a greater understanding of these elusive neural formations may shed light on key components of developing treatments for neuropsychiatric and movement disorders. However, previous attempts to investigate CStr and CStc connections have produced confounding results. We hypothesized that, within the striatum, corticostriatal and corticospinal projections innervate distinct postsynaptic targets, wherein one’s removal will induce deficits in acquisition and performance. To map axonal projections and specify the location of postsynaptic cells, a viral intersect strategy was used. Expression of Cre recombinase was achieved by retrograde infection with AAV virus from either striatal or spinal innervation sites. Subsequent targeting of either a Cre-dependent axonal tracer or Cre-dependent HSV for transynaptic anterograde tracing permitted specific infection of either corticostriatal or corticospinal cells. Subsequent neuropeptide labeling was used to distinguish postsynaptic striatal partners (indirect or direct) for both neuronal tracts. The functional contribution of each motor system was assessed in a skilled forelimb reach task. Corticostriatal ablation (n = 4) was achieved by viral expression of a diphtheria toxin receptor system, and specific circuit silencing (n = 4) was achieved using viral expression of a Cre-dependent DREADD system (designer receptor exclusively activated by designer drug) and subsequent ligand administration (CNO). Antagonistic effects on motor performance were evaluated. Results suggested that CStr does not play a significant role in acquisition or motor performance (p > 0.05). The ability to localize CStr and CStc projections within the striatum will carry practical applications for both research and translational medicine.

    FRI-849 THE IMPACT OF KAINATE RECEPTORS ON SPINAL CORD DEVELOPMENT

    • Bryan McClarty ;
    • Claire Vernon ;
    • Yomayra Guzman ;
    • Geoffrey Swanson ;

    FRI-849

    THE IMPACT OF KAINATE RECEPTORS ON SPINAL CORD DEVELOPMENT

    Bryan McClarty, Claire Vernon, Yomayra Guzman, Geoffrey Swanson.

    Northwestern University, Chicago, IL.

    Development of the peripheral nervous system is crucial for proper perception of environmental cues. Dorsal root ganglia (DRG) sensory neurons connect peripheral tissue to the spinal cord with nociceptive C-fibers and innocuous-sensing Aβ-fibers. Kainate receptors (KARs, GluK1-5), a subfamily of ionotropic glutamate receptors, are expressed in C-fibers where they act as peripheral chemosensors, regulate central transmitter release, and modulate neurite outgrowth. Our lab has found that Neto2, a KAR auxiliary subunit, is highly expressed in neonatal DRG neurons and downregulated at older ages. Given that DRG fiber growth into the spinal cord finishes concurrently with Neto2 downregulation, we hypothesized that Neto2-containing KARs impact DRG fiber spinal maturation. To test this hypothesis, lumbar spinal cord from wild-type, GluK1- and Neto2-knock-out (Neto2-KO) mice at P3, P22, and 8 weeks old were stained for neurofilament-200 and with isolectin B4 to identify Aβ and C fibers, respectively. Fiber lamination in sections imaged by confocal microscopy appears normal in adult Neto2-KO mice, but the innervation density in each lamina remains to be quantified. The developmental timecourse of fiber innervation also remains to be determined. These experiments will deepen our understanding of KAR contribution to sensory circuit development, an essential foundation for sensory signaling.

    THU-852 PTSD: EFFECT OF POST-TRAUMATIC STRESS ON HIPPOCAMPAL MEMORY REPLAY

    • Maria Carmen Varela ;
    • David Jaffe ;

    THU-852

    PTSD: EFFECT OF POST-TRAUMATIC STRESS ON HIPPOCAMPAL MEMORY REPLAY

    Maria Carmen Varela, David Jaffe.

    The University of Texas at San Antonio, San Antonio, TX.

    Approximately 24.4 million Americans will suffer from post-traumatic stress disorder (PTSD) at some point in their life. Sharp wave ripples (SWR) are commonly seen during slow wave sleep when memories are being replayed, however we do not know how post-traumatic stress affects SWR activity. We hypothesize that excessive and aberrant replay of hippocampal memories, in the form of increased, intensified or prolonged SWRs, may be a direct result of traumatic stress. This hypothesis is supported by the observation that SWR-like activity is enhanced in rat hippocampal slices following fear conditioning. We will test this hypothesis by implanting electrodes into the hippocampi of 2 groups of rats. One group will be exposed to chronic immobilization stress (CIS) consisting of 2 hours of immobilization per day for 10 days. A second, unstressed group will serve as controls. We will then take EEG recordings of SWR activity in the hippocampus and compare them between the stressed and nonstressed groups. We expect to find that CIS will cause an increase of SWR occurrence suggesting abnormal and excessive memory replay. A thorough understanding of the effects of stress on hippocampal memory consolidation and the impact of stress on the occurrence of SWRs will be important for improving the quality of existing treatments and the development of new therapies for PTSD.

    THU-781 A BEHAVIORAL AND ELECTROPHYSIOLOGICAL STUDY OF NOCICEPTION IN MANDUCA SEXTA

    • Allan Solis ;
    • Dennis Tabuena ;
    • Megumi Fuse ;

    THU-781

    A BEHAVIORAL AND ELECTROPHYSIOLOGICAL STUDY OF NOCICEPTION IN MANDUCA SEXTA

    Allan Solis, Dennis Tabuena, Megumi Fuse.

    San Francisco State University, San Francisco, CA.

    Studying nociception in vertebrates is mired in ethical quandaries and can be cost prohibitive. However, invertebrates have many of the same responses to noxious stimuli and fewer constraints. The insect Manduca sexta, has an established defensive strike reflex to noxious stimuli, and our goal was to characterize the electrophysiological responses to a noxious stimulus (a pinch). We used 3 assays: an established in vivo assay involved measurements with von Frey filaments; an in situ preparation with an intact anterior portion of the insect for videography and an exposed posterior nervous system for extracellular electrophysiological recordings; and an in vitro isolated nervous system preparation, with one ganglion and associated nerves attached to a portion of body wall. The in vivo assay resulted in significant reduction in force required to initiate a strike after pinching, suggesting that the animal had become sensitized. The in situ assay showed a correlation between the defensive strike and electrical activity. The in vitro assay allowed us to identify the afferent nerve responsible for transmitting the pinch by sequentially cutting each nerve until the response to the pinch was lost. We now have numerous assays to further study nociception in M. sexta, to determine how and where sensitization occurs in the nervous system. This research provides access to a cheaper and more feasible model for studying nociception, which may be translated to conditions such as neuropathic pain that afflict higher order organisms.

    THU-857 TESTING THE GATE HYPOTHESIS FOR SEIZURE DEVELOPMENT: MUSCARINIC RECEPTOR MODULATION OF INPUT/OUTPUT THROUGH THE DENTATE GYRUS

    • Kael McInnis ;
    • Jessica Perkins ;
    • Robert Brenner ;
    • Mark Shapiro ;
    • David Jaffe ;

    THU-857

    TESTING THE GATE HYPOTHESIS FOR SEIZURE DEVELOPMENT: MUSCARINIC RECEPTOR MODULATION OF INPUT/OUTPUT THROUGH THE DENTATE GYRUS

    Kael McInnis1, Jessica Perkins1, Robert Brenner2, Mark Shapiro2, David Jaffe1.

    1The University of Texas at San Antonio, San Antonio, TX, 2The University of Texas Health Science Center at San Antonio, San Antonio, TX.

    Traumatic brain injury is a leading cause of temporal lobe epilepsy in humans and is usually accompanied by behavioral stressors, most notably during combat. Both stress and novelty modulate transmission through the hippocampal formation, a temporal lobe structure highly prone to epileptic activity. The dentate gyrus (DG) serves as both a gate and a filter for information flowing into the hippocampus. Low-frequency signals readily pass through this structure, while blocking high-frequency signals. Extreme stress elevates cholinergic signaling. We hypothesize that muscarinic cholinergic receptor activation promotes seizure development by reducing the gating function of the DG. Using a mouse hippocampal slice preparation, we studied the effects of muscarinic receptor activation on signal propagation through the DG. Bath application of the muscarinic agonist carbachol (CCh, 20 µM) resulted in a shift in the optimum frequency for signal transmission from 5 to 50 Hz. Analyses of evoked perforant-path synaptic input, and the resulting population spike output, suggests that enhanced signal propagation results from an increase in postsynaptic excitability, maximal at 50 Hz. CCh had no significant effect on low-frequency (5 Hz) transmission. These results are consistent with the hypothesis that stress-associated neuromodulation alters DG gating. Future experiments will employ a designer receptor exclusively activated by designer drugs (DREADD) approach where we will exclusively increase the excitability of DG granule cells, without affecting the entire DG network, to further understand how stress-associated modulation affects DG gating.  [Partially funded by GM060655.]

    THU-845 USING FLUORESCENT IMAGING TO EVALUATE THE MECHANISMS OF MEMANTINE ON SPREADING DEPOLARIZATION

    • Alanna Humphrey ;
    • C.W. Shuttleworth ;
    • Kate Reinhart ;

    THU-845

    USING FLUORESCENT IMAGING TO EVALUATE THE MECHANISMS OF MEMANTINE ON SPREADING DEPOLARIZATION

    Alanna Humphrey1, C.W. Shuttleworth2, Kate Reinhart2.

    1Xavier University of Louisiana, New Orleans, LA, 2The University of New Mexico, Albuquerque, NM.

    Spreading depolarization (SD) is a slowly propagating “tsunami” of severe and long-lasting neuronal depolarization, characterized by massive ion translocation. Excessive release of glutamate neurotransmitter during SD over activates N-methyl-D-aspartate receptors (NMDAR) and likely contributes to the progression of acute brain injury. One method that has been used to reduce the consequences of SD is NMDAR blockers such as ketamine. Memantine, another NMDAR blocker approved for clinical use, has shown promising results by reducing the number of SDs in vivo; however, it is unknown if memantine affects glutamate release or duration of SD. We evaluated the effect of memantine on SD using electrophysiological and fluorescent recordings in hippocampal slices prepared from C57BL/6 mice. SD was initiated by focal microinjection of KCl in the presence and absence of memantine. Memantine slowed both SD propagation rate (p = 0.001) and the duration of depolarization as measured by direct current (DC) potential changes (p < 0.0001). Since glutamate and zinc are co-packaged in presynaptic vesicles, synaptic zinc was measured using extracellular FluoZin3 as a proxy for glutamate release. Using this technique, we found that memantine prolonged the duration of zinc transients compared to controls (p = 0.0135). This finding suggests that decrease in glutamate release was not responsible for shorter SD duration. Since shorter SD durations are correlated with improved functional recovery, the postsynaptic effects of memantine show promise for future clinical application.

    THU-783 INFECTION WITH TYPE II TOXOPLASMA GONDII PROTECTS AGAINST AMYLOID-B DEPOSITION IN A MOUSE MODEL OF ALZHEIMER'S DISEASE

    • Jenna Franco ;
    • Carla Cabral ;
    • Wes McDonald ;
    • Anita Koshy ;

    THU-783

    INFECTION WITH TYPE II TOXOPLASMA GONDII PROTECTS AGAINST AMYLOID-B DEPOSITION IN A MOUSE MODEL OF ALZHEIMER'S DISEASE

    Jenna Franco, Carla Cabral, Wes McDonald, Anita Koshy.

    The University of Arizona, Tucson, AZ.

    Alzheimer’s disease (AD) is an incurable brain disorder affecting millions of people worldwide. AD is characterized by progressive neurodegeneration and deposition of amyloid-beta (Aβ) plaques that are exacerbated by increased inflammation in the brain. Toxoplasma gondii is an obligate intracellular parasite known for its ability to persist in the central nervous system (CNS) by evading host immune responses. Interestingly, a recent study in an AD mouse model demonstrated that mice chronically infected with Toxoplasma were protected against the development of AD-like pathology compared to uninfected controls. Based on this report and our understanding of Toxoplasma strain differences, we hypothesized that only strains of Toxoplasma causing a persistent CNS infection and inflammatory response would be neuroprotective. To test this hypothesis, we infected AD mice with strains of Toxoplasma (Type I, Type II, or Type III) known to cause different CNS immune responses. At 6 months post infection, we compared CNS Aβ plaque deposition and immune responses in infected mice to uninfected controls. We found that Type I-infected mice, which do not develop a persistent CNS infection, were no different than the controls. Of the persistent Toxoplasma strains (Type II and Type III), only Type II infection reduced Aβ plaque burden, even though both strains were associated with elevated CNS levels of anti-inflammatory cytokines. Future studies will focus on defining the mechanisms underlying the Type II neuroprotective effect. Understanding these mechanisms could reveal novel drug targets for AD.

    THU-851 THE LOSS OF ALPHA2DELTA-1 DISRUPTS EXCITATORY SYNAPTOGENESIS AND CORTICAL STRUCTURE AND MAY BE A LINK TO EPILEPSY AND HYPEREXCITABILITY

    • Charlene Rivera ;
    • Lauren Andresen ;
    • Chris Dulla ;

    THU-851

    THE LOSS OF ALPHA2DELTA-1 DISRUPTS EXCITATORY SYNAPTOGENESIS AND CORTICAL STRUCTURE AND MAY BE A LINK TO EPILEPSY AND HYPEREXCITABILITY

    Charlene Rivera1, Lauren Andresen2, Chris Dulla2.

    1University of Puerto Rico in Cayey, Cayey, PR, 2Tufts University School of Medicine, Boston, MA.

    Alpha2delta-1 (α2δ-1) is a calcium channel subunit known for its role in enhancing calcium channel trafficking and shaping neurotransmitter release. Interestingly, recent studies have shown that α2δ-1 is also involved in excitatory synaptogenesis in the cortex during development. The synaptogenic actions of α2δ-1 rely on its ability to bind its ligand, astrocyte secreted thrombospondins (TSP). Altered TSP/α2δ-1 activity has been implicated in several disease states, such as epilepsy. Previous work has shown that α2δ-1 knock-out (KO) mice exhibit hyperexcitability as assessed by evoked cortical field potential recording. We hypothesize that the loss of α2δ-1 during development leads to hyperexcitability by altering synaptogenesis and cortical structure. To approach this, immunohistochemistry was performed in α2δ-1 KO and wild-type littermates to examine cortical structure development, synapse number alteration, and astrocyte regulation. Synapse number was determined by counting the close appositions of pre and post synaptic terminal markers PSD95 and vGlut1. Cortical development was evaluated using the cortical layer markers CTIP2 and CUX1. Excitatory/inhibitory balance was analyzed using neuronal marker NeuN and interneuron marker Parvalbumin. Astrocyte regulation was also determined using astrocyte marker GFAP. Results showed a decreased number of excitatory synapses, ectopic CTIP2 positive cells in the outer layer of the cortex, increased amount of neurons and astrocyte upregulation. Understanding the mechanism of hyperexcitability in the absence of α2δ-1 will shed light on the normal role of α2δ-1 during development, and pathological compensatory changes that occur due to loss of α2δ-1.

    FRI-838 MAGNETIC RESONANCE IMAGING OF LIPOPOLYSACCHARIDE INDUCED SEPTIC ENCEPHALOPATHY IN THE RAT MODEL

    • Katelyn Whitaker ;
    • Derbra Saunders ;
    • Nataliya Smith ;
    • Kathryn Morton ;
    • Rheal Towner ;

    FRI-838

    MAGNETIC RESONANCE IMAGING OF LIPOPOLYSACCHARIDE INDUCED SEPTIC ENCEPHALOPATHY IN THE RAT MODEL

    Katelyn Whitaker1, Derbra Saunders1, Nataliya Smith1, Kathryn Morton2, Rheal Towner1.

    1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, 2University of Utah Health Sciences Center, Salt Lake City, UT.

    Magnetic resonance imaging (MRI) techniques were used to detect neuro-inflammation, and damage to the blood brain barrier (BBB), resulting from experimental sepsis. Lipopolysaccharide (LPS) was injected into 8 male rats to induce sepsis. A control group, also 8 male rats, were injected with saline solution. The brains of both of the experimental and the control groups were imaged using MRI techniques. The rats were imaged at 24 hours, 1 week, and 3 weeks to observe neuro-inflammation and the disruption of the BBB. The scans were diffusion weighted imaging (DWI) and contrast-enhanced morphological imaging. During the morphological scans, the contrasting agent gadolinium was injected to highlight changes in the BBB. Rats were injected with the gadolinium after a pre-contrast morphological scan and DWI was performed. The region of the brain targeted for analysis was the hippocampus. We statistically analyzed 6 rats for each group, with 2 datasets removed as outliers. After 24 h, the morphological images, which were analyzed to show percent change in MRI signal intensity (SI), demonstrated a significant increase in BBB disruption in the LPS-exposed group (p < 0.05) compared to controls. At the same time point of 24 h, the DWI data showed an increase in percent change of the apparent diffusion coefficient (ADC) for LPS rats (p < 0.01) compared to controls. Data from other time points were also assessed. This study indicates that MRI techniques can be used to assess early changes in septic encephalopathy.

    FRI-783 EFFECTS OF A HIGH FAT DIET ON OXYTOCIN RECEPTORS IN THE BRAINSTEM

    • Julie Ngo ;
    • Karen Bales ;

    FRI-783

    EFFECTS OF A HIGH FAT DIET ON OXYTOCIN RECEPTORS IN THE BRAINSTEM

    Julie Ngo, Karen Bales.

    University of California, Davis, Davis, CA.

    While the hormone oxytocin (OT) is known for its role in childbirth, maternal bonding, and lactation, recently studies have suggested that OT can play a role in body weight regulation through several different circuits. Obesity and other metabolic disorders are an important chronic health issue, and OT could have an exciting potential use as a therapy. The relationship between OT and reduced feeding is thought to be mediated through OT receptors in brainstem areas linked to the regulation of meal size (e.g., nucleus of the solitary tract (NTS)). To further evaluate the relationship between OT and body weight, we used a diet-induced obesity model in adult male rats, which were given unlimited water and either a high-fat diet or rodent chow and received chronic infusions of either vehicle (saline) or OT (16 nmol/day) into the third ventricle. Our goal is to identify the extent to which alterations in OT receptor binding in the NTS may contribute to OT’s anorexigenic effects in diet-induced obese (DIO) rats. We expect higher binding in DIO animals than lean animals and lower binding in those treated with OT than in those treated with saline. The method used to assess binding will be receptor autoradiography.

    THU-780 AXON-TO-CELL-BODY SIGNALING EFFECTS ON NEURONAL MRNA LEVELS USING BRAIN-DERIVED NEUROTROPHIC FACTOR

    • Yacouba Sidibe ;
    • Orlangie Natera ;
    • Bill Mobley ;

    THU-780

    AXON-TO-CELL-BODY SIGNALING EFFECTS ON NEURONAL MRNA LEVELS USING BRAIN-DERIVED NEUROTROPHIC FACTOR

    Yacouba Sidibe1, Orlangie Natera2, Bill Mobley2.

    1Bucknell University, Lewisburg, PA, 2University of California, San Diego, La Jolla, CA.

    Neurons are complex, polarized cells with subcellular domains that vary in morphology and function and rely on extracellular cues for survival. There is limited information, however, regarding the molecular mechanism responsible for axon growth induced by one such cue, brain-derived neurotropic factor (BDNF). Through a series of experiments, this investigation measured changes in the levels of certain messenger RNAs (mRNAs) in both the axon and cell body of neurons, as they respond to retrograde (axon-to-cell-body) BDNF signaling. We hypothesized that BDNF is responsible for up regulating mRNA transcripts of proteins that aid in the facilitation of axonal maintenance and growth. To demonstrate this, cultures containing neurons from the hippocampus of embryonic rats were prepared. An apparatus allowing microfluidic separation of axons from their cell bodies was employed. After one week in vitro, the experimental group was treated with BDNF. Using quantitative PCR, changes were recorded in the levels of mRNAs coding for cytoskeletal and structural proteins between groups. If supported, these findings will enrich our understanding of neuronal signaling and how it may relate to diseases such as Alzheimer’s and Down's syndrome.

    FRI-852 USE OF CRISPR/CAS9 TO ADDRESS THE ROLE OF CHONDROITIN SULFATE BIOSYNTHESIS PATHWAY ENZYMES IN AXON-GLIAL INTERACTION

    • Sofia Gasperino ;
    • Sudheendra Rao ;

    FRI-852

    USE OF CRISPR/CAS9 TO ADDRESS THE ROLE OF CHONDROITIN SULFATE BIOSYNTHESIS PATHWAY ENZYMES IN AXON-GLIAL INTERACTION

    Sofia Gasperino1, Sudheendra Rao2.

    1Virginia Polytechnic Institute and State University, Blacksburg, VA, 2University of Miami, Coral Gables, FL.

    Downregulation of chondroitin sulfate proteoglycan (CSPG) synthesis after an injury to the spinal cord leads to an increase in axonal regeneration caudal to the glial scar formed. In Schwann cells, this downregulation has been shown to assist them in penetrating deeper into the astrocyte scar. Due to the supportive roles of CSPGs, it is important to decipher the roles of individual enzymes in the CSPG biosynthesis pathway in glial cells and in axon-glial interaction. We want to address this by developing CRISPR/Cas9-mediated genome editing in glial model cells. We begin by using CRISPR/Cas9 to create knockout cells that lack 2 important chondroitin sulfate (CS) synthesizing enzymes of interest: chondroitin sulfate synthase 1 and chondroitin-4-sulfate transferase. Our ultimate goal is to determine whether the modified Schwann cells promote axonal regeneration/penetration past the astrocyte boundary. We will accomplish this by observing the interaction between the glial cell knockouts with axons as well as with astrocytes when these enzymes are absent. We were successful in creating sequence-verified CRISPR knockout constructs for CHSY1 and CHST11. We showed that transfection of this construct in mouse neuroblastoma cells, rat astrocyte cell line, mouse Schwann cell line, and rat primary Schwann cells was successful and did not produce any cell death or morphological changes. Confirmation of CRISPR/Cas9-induced mutations in the transfected cells as well as single colony isolation of rat Schwann cells remains ongoing. This study advances the effort to use glial cells for transplantation and regrowth of axons post spinal cord injury.

    THU-853 ENHANCING CJUN ACTIVITY TO PROMOTE NEURITE OUTGROWTH

    • Kimberly Rose Madhwani ;
    • Saloni Mehta ;
    • Vance Lemmon ;
    • John Bixby ;

    THU-853

    ENHANCING CJUN ACTIVITY TO PROMOTE NEURITE OUTGROWTH

    Kimberly Rose Madhwani1, Saloni Mehta2, Vance Lemmon2, John Bixby2.

    1California State University, Northridge, Northridge, CA, 2University of Miami, Coral Gables, FL.

    The peripheral nervous system (PNS) has the ability to regenerate axons over long distances following an injury. On the other hand, axons in the central nervous system (CNS) are unable to regenerate efficiently after injury due to both intrinsic and extrinsic factors. There are numerous genes known to regulate successful regeneration in the PNS. The transcription factor cJun has been found to be upregulated after injury and to promote regeneration in the PNS. In the CNS, the role of cJun in axon regeneration is still not well understood. In previous studies, the overexpression of the cJun in cortical neurons was shown to promote axon outgrowth in vitro as well as axon regeneration ex vivo. Though wild-type cJun can promote some axonal regeneration, we want to enhance this activity in order to increase the chances of functional recovery in the CNS. We fused cJun to each of 2 transactivation domains, VP16 and VP64, known to increase the expression of genes bound to associated transcription factors, and overexpressed these constructs in postnatal day-3 cortical rat neurons. We hypothesized that the addition of these transactivation domains to cJun would allow increased promotion of neurite outgrowth in primary cortical neurons. From the data gathered from this study, we concluded that the addition of activation domains VP16 and VP64 significantly promotes total neurite outgrowth. Since VP16-Jun and VP64-Jun significantly promote neurite outgrowth in vitro, they would be ideal candidates to overexpress in vivo to promote axon regeneration.

    FRI-766 MICROENDOSCOPIC IMAGING OF CELL-TYPE-SPECIFIC NEURONAL ACTIVITY IN THE BASAL FOREBRAIN IN FREE-MOVING MICE AND HEAD-FIXED MICE DURING GOAL-DIRECTED BEHAVIOR

    • Pedro Guzman ;
    • Thomas Harrison ;
    • Yang Dan ;

    FRI-766

    MICROENDOSCOPIC IMAGING OF CELL-TYPE-SPECIFIC NEURONAL ACTIVITY IN THE BASAL FOREBRAIN IN FREE-MOVING MICE AND HEAD-FIXED MICE DURING GOAL-DIRECTED BEHAVIOR

    Pedro Guzman, Thomas Harrison, Yang Dan.

    University of California, Berkeley, Berkeley, CA.

    The basal forebrain is considered the sole source of cholinergic input to the cortex. Cholinergic activity is related to sleep states, consciousness, and attention. Cholinergic neurons make up a minority of the basal forebrain’s neurons and are intermixed with glutamatergic and GABAergic neurons. Much remains unknown about the relationship between these cell types and their behavioral performance. Here, we performed cellular-resolution Ca2+ imaging of cholinergic, glutamatergic, and GABAergic neurons in the basal forebrain that were transduced with adeno-associated virus in order to express GCaMP. Expression of GCaMP was verified using fluorescence in situ hybridization and immunostaining. The use of microendoscopes allowed optical access to the basal forebrain and observation of neural activity. Moreover, behavioral data collected from free-moving mice were analyzed together with in vivo imaging data in order to map the activation of different types of cells in the basal forebrain during different behaviors. Neuronal activity was also studied during a simple discrimination task to determine the activity of basal forebrain neurons during goal-directed behavior. These experiments represent the first cell-type-specific observations of basal forebrain activity and provide new insights into the function of this brain region.

    FRI-854 THE EFFECTS OF MATERNAL IMMUNE ACTIVATION AND GABRB3 DEPLETION ON THE MITOTIC INDEX OF NEURAL PROGENITOR CELLS IN THE DEVELOPING FETAL BRAIN

    • Alyssa Bormann ;
    • Theo Palmer ;
    • Amy HyangMi Moon ;

    FRI-854

    THE EFFECTS OF MATERNAL IMMUNE ACTIVATION AND GABRB3 DEPLETION ON THE MITOTIC INDEX OF NEURAL PROGENITOR CELLS IN THE DEVELOPING FETAL BRAIN

    Alyssa Bormann1, Theo Palmer2, Amy HyangMi Moon2.

    1California State University, Fullerton, Fullerton, CA, 2Stanford University, Stanford, CA.

    Maternal immune activation (MIA) during early pregnancy is accompanied by an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Previous research has shown that innate immune activation by lipopolysaccharide (LPS) in mice during early pregnancy compromises placental function and decreases the number of proliferating neural progenitor cells. Additionally, GABRB3 deletion has been linked to a variety of neurodevelopmental disorders, and the GABRB3 gene-deficient mouse has proven to be an interesting model for examining the etiology of ASD. We believe that environmental factors and genetic background may have synergistic effects in increasing the risk and severity of neurodevelopmental disorders. Here, we show that LPS-induced MIA in combination with a GABRB3 mutation synergize in causing neuroproliferative defects in the fetal brain. To evaluate neural progenitor cell proliferation, E13.5 fetal brains from immune-challenged and control pregnancies were stained and counted for the abundance of phospho-histone, H3-positive mitotic cells. This period reveals a critical stage of development in which the brain is undergoing high levels of neurogenesis, migration, and differentiation. Our research will determine if there is a significant decrease in the number of mitotic neural progenitor cells in fetuses carrying the mutant GABRB3 gene relative to controls. A more pronounced effect would be consistent with the observation in humans that MIA during early gestation as well as genetic background have been linked to neurodevelopmental disorders in the child. These studies could have implications for evaluating the significance of genetic and environmental factors in ASD and other neurodevelopmental disorders.

    FRI-846 THE MEDIAL PREFRONTAL CORTEX AS A MODULATOR IN FOOD REWARD MOTIVATION

    • Alyssa Brunal ;
    • Daniel Warthen ;
    • Michael Scott ;

    FRI-846

    THE MEDIAL PREFRONTAL CORTEX AS A MODULATOR IN FOOD REWARD MOTIVATION

    Alyssa Brunal1, Daniel Warthen2, Michael Scott2.

    1Virginia Polytechnic Institute and State University, Blacksburg, VA, 2University of Virginia, Charlottesville, VA.

    Over 60% of the U.S. is considered overweight or obese. Because of the health risks associated with obesity, this problem must be addressed. The medial prefrontal cortex (mPFC) is an area of the brain associated with decision making. While in the presence of a reward, it is believed to calculate the risks and benefits associated with obtaining that reward. The nucleus accumbens (NAc), another brain region, integrates information from the mPFC and other areas of the brain to initiate reward-related motor activity. We hypothesized that the mPFC-to-NAc connection is involved in the motivation to seek a food reward. To test this, we used chemogenetics to selectively stimulate this pathway using the engineered muscarinic receptor M3Dq and ligand clozapine-n-oxide (CNO). Mice were trained to nosepoke for a food reward then subsequently tested during stimulation of mPFC-to-NAc neurons. During testing, the rewards were dispensed on a progressive scale, with more pokes required for each additional reward. The point at which they are unable to complete a stage is labeled the break point and was used to determine reward-seeking motivation. We completed the testing over 2 days. Each mouse received a CNO injection on one day and a saline injection another day to act as a control. When fed, there was no effect on break point. However, when fasted, there is a significant difference between CNO-treated versus saline-treated mice, indicating that the role of this pathway in modulating food reward differs depending on whether the animal is sated or fasted.

    FRI-856 THE ROLE OF ALBUMIN-INDUCED TGFB SIGNALING IN AGE-RELATED SEIZURE VULNERABILITY

    • Chelsy Eddings ;
    • Vladimir Senatorov ;

    FRI-856

    THE ROLE OF ALBUMIN-INDUCED TGFB SIGNALING IN AGE-RELATED SEIZURE VULNERABILITY

    Chelsy Eddings1, Vladimir Senatorov2.

    1University of California, Berkeley, Berkeley, CA, 2Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA.

    Post-traumatic epilepsy (PTE), occurring after brain insult, is one of the most common epilepsies, affecting millions worldwide. The progression of PTE is marked by a silent period where post-injury inflammatory responses are thought to contribute to a hyperexcitable neural environment leading to seizures. Since post-injury epilepsy is often resistant to antiseizure medications, elucidating the mechanisms of the silent period of epileptogenesis may reveal preventative treatments. Our previous research found that breakdown of the blood-brain barrier, characteristic of injury, allows the blood protein albumin to enter the brain. Albumin binds selectively to transforming growth factor beta receptors (TGF-βR) on astroglia, causing inflammatory TGF-β signaling, initiating reactive astrocytosis, and increasing epileptogenesis. Furthermore, pharmacologically blocking albumin binding of TGF-βR prevents activation signaling and seizure activity in rodents exposed to albumin. Interestingly, the occurrences of seizures significantly increases in the elderly, but the causes of age-related vulnerability remain elusive. Probing the possible roles of potentially epileptogenic astrocytes in causing seizure susceptibility may explain the molecular factors underlying increased epileptogenesis in aged brains. We hypothesize that the aged brain will show heightened astrocytic reactivity to albumin signaling, resulting in increased vulnerability to albumin-induced epilepsy. To test this, we characterized the astrocyte response to albumin in both young and aged mice. We quantified albumin signal transduction and used specific transgenic approaches to analyze astrocytosis and block astrocytic TGF-β signaling, assessing the effects of astrocyte signaling and age on seizure induction threshold. These experiments explore the potential for preventative treatments targeting astrocyte reactivity before epilepsy onset.

    FRI-837 THE EFFECT OF HIGH-FAT DIET ON MUSCLE STRETCH SENSITIVITY

    • Kassina Kim-Hayes ;
    • Lubayana Elahi ;
    • Krystle Shamai ;
    • Samson Tang ;
    • Katherine Wilkinson ;

    FRI-837

    THE EFFECT OF HIGH-FAT DIET ON MUSCLE STRETCH SENSITIVITY

    Kassina Kim-Hayes1, Lubayana Elahi2, Krystle Shamai2, Samson Tang2, Katherine Wilkinson2.

    1Macalester College, Saint Paul, MN, 2San Jose State University, San Jose, CA.

    Obesity has become a prominent public health issue. Obese individuals have shown more trouble with balance and are more likely to fall than nonobese individuals. Balancing the body involves proprioception, the ability to sense one’s body position, which relies on muscle spindle afferents, nerves that innervate muscle spindles and detect muscle stretch to alert the brain of a muscle’s status. We believe that the difficulty in balance seen with obese individuals is in part due to these muscle spindle afferents. Our lab has previously shown insensitivity of muscle spindle afferents in male mice fed a high-fat diet. This insensitivity could help explain why obese individuals have impaired balance. We are testing the hypothesis that female mice fed a high-fat diet will not show similar impaired muscle stretch sensitivity like the male mice in our previous studies. To test this, we used a control group of mice that were fed a regular diet (10% kCal from fat), and a high-fat-diet group of mice (60% kCal from fat), all female. After dissection, we weighed the reproductive fat pads, spleen, and kidney, and measured blood glucose levels to compare how female mouse weight gain and metabolic markers differ from males. We then measured the response of the muscle spindle afferents to 3 stretch lengths by physically stretching the muscle to determine if high-fat female mice showed impaired stretch sensitivity. If our hypothesis is supported, the results could give us insight into human obesity and the cause of the proprioceptive difficulties that come with obesity.

    FRI-782 THE LATE POSITIVE ERP IN LANGUAGE PROCESSING

    • Maxwell Ruckstuhl ;
    • Megan Bardolph ;
    • Seana Coulson ;

    FRI-782

    THE LATE POSITIVE ERP IN LANGUAGE PROCESSING

    Maxwell Ruckstuhl, Megan Bardolph, Seana Coulson.

    University of California, San Diego, La Jolla, CA.

    Electroencephalography (EEG) is a noninvasive measure of brain activity that has proven especially valuable in the study of neural information processing. Event-related potentials (ERPs) are cross-trial averages of EEG signals following a stimulus. ERP parameters, including timing, amplitude, and distribution, have been shown to index discrete components of language processing. By analyzing ERPs across stimulus conditions, we can break down the complex problem of understanding language and glean insight about the brain's activity over time and space. In this study, we examined 2 theories regarding the post-N400 positivity (PNP), an ERP component that has been shown to index both syntactic and semantic violation. We hypothesized that a parietal PNP is caused by the forced reinterpretation of a sentence, including syntactic violation. Independently, a frontal PNP indexes incorrect word prediction including semantic violation. To evaluate these hypotheses, we took EEG measurements at 32 standard scalp locations on 19 subjects who were presented with 290 sentences under 4 conditions to elicit the separate PNPs. We observed a PNP consistent with our prediction of the frontal PNP, but it was distributed across both the frontal and parietal lobes, precluding confirmation of our theory. Improved stimuli that more selectively elicit the 2 PNPs may allow us to tease out the differences. Nevertheless, this finding supports the use of ERPs as a valuable tool in cognitive science to determine how the brain processes information and how it reacts to different unexpected stimuli.

    FRI-853 DEVELOPMENT OF GFAP EXPRESSION IN THE OPTIC NERVE OF ZEBRAFISH

    • Zara Flores ;
    • Dana Garcia ;

    FRI-853

    DEVELOPMENT OF GFAP EXPRESSION IN THE OPTIC NERVE OF ZEBRAFISH

    Zara Flores1, Dana Garcia2.

    1Northwest Vista College, San Antonio, TX, 2Texas State University, San Marcos, TX.

    The specific aim of this research is to test whether Gfap expression in the optic nerve of zebrafish is age dependent. This aim supports the overarching goal of determining whether the zebrafish optic nerve is a good model system in which to study age-related changes in the central nervous system relevant to human health. Gfap is an intermediate filament protein expressed in a cell-specific manner by astrocytes; however, previously published work has shown that astrocytes in the optic nerve of zebrafish do not express Gfap. More recently, we observed green fluorescent protein expression in the optic nerve of a 24-month old, transgenic, gfap:GFP zebrafish. Since previous work had been done on younger, adult fish (6 - 8 months old), we hypothesized that appearance of GFP in the retina signified age-related changes. To test this hypothesis, we performed immunohistochemistry and confocal microscopy on fish aged 6 – 48 months using an anti-GFAP antibody known to recognize zebrafish Gfap. Our preliminary results suggest that 6-month old fish express Gfap in the retina and brain, but not in the optic nerve. In contrast, every fish examined ranging in age from 8 – 48 months showed Gfap-labeling in the optic nerve. We conclude Gfap expression is age-dependent, but that the switch occurs while the fish are still reproductively competent. Further examination will include more fish and younger fish. In future studies, we will examine expression of the senescence marker p16 as well to see if it correlates with Gfap expression in the optic nerve.

    THU-850 ANIMAL MODELS OF VISCERAL PAIN: CHALLENGES & OPPORTUNITIES

    • Maeghan Murie ;
    • Ehsan Mohammadi ;
    • Beverley Meerveld Greenwood-Van ;

    THU-850

    ANIMAL MODELS OF VISCERAL PAIN: CHALLENGES & OPPORTUNITIES

    Maeghan Murie, Ehsan Mohammadi, Beverley Greenwood-Van Meerveld.

    University of Oklahoma Health Sciences Center, Oklahoma City, OK.

    Visceral pain is a hallmark feature in the pathophysiology of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Although IBS accounts for nearly $30 billion spent on health care per year, it remains a poorly treated condition due to a lack of understanding of the mechanisms behind visceral pain. Experimental models provide a pathway to gain a better understanding of the mechanisms underlying visceral pain and will play a pivotal role in the development of new treatments for patients with visceral pain. This presentation will provide 1) a brief overview of existing animal models of visceral pain, 2) outline what we have learned from these models, and 3) discuss the challenges and opportunities associated with using these models to develop novel therapeutic approaches to treat visceral pain.

    THU-856 ASSESSING GONADOTROPIN-RELEASING HORMONE NEURONS IN THE BRAINS OF DIFFERENT MOUSE STRAINS

    • Diana Arroyo ;
    • Scott Kavanaugh ;
    • Samantha Bonelli ;
    • Pei-San Tsai ;

    THU-856

    ASSESSING GONADOTROPIN-RELEASING HORMONE NEURONS IN THE BRAINS OF DIFFERENT MOUSE STRAINS

    Diana Arroyo1, Scott Kavanaugh2, Samantha Bonelli2, Pei-San Tsai2.

    1Arizona State University, Tempe, AZ, 2University of Colorado Boulder, Boulder, CO.

    Gonadotropin-releasing hormone (GnRH) is a neurohormone released by GnRH neurons to stimulate the secretion of gonadotropins from the anterior pituitary. As such, GnRH neurons are indispensable for reproductive activation and fertility. Typical numbers of GnRH neurons in mice are around 600 – 1,200, though the numbers are strain dependent. For this experiment, 3 different non-transgenic mixed strains were looked at: Line One Control Old (LIC Old), Line One Control New (LIC New), and wild-type R3 (WT R3). The LIC Old strain was no longer appropriate as a control because its transgenic counterpart was re-derived in a different genetic background, so a new strain, LIC New, was made; however, this new strain needed to be tested to see if it could be used as a replacement for the old strain. To test this, mouse brains from the 3 strains were fixed in paraformaldehyde, sectioned in a cryostat, and the sections subjected to immunohistochemistry to identify GnRH neurons. These sections were then mounted onto slides and observed under a microscope to count the total number of GnRH neurons by an observer blind to the identity of the brains on the slides. There was no significant difference between the 3 groups, and a test to determine if there was any sex difference in the number of GnRH neurons between the LIC mice also showed that there was no significant difference.

    THU-769 TRACKING THE WORM HEAD: EXAMINING THE GENESIS OF BEHAVIOR IN THE DEVELOPING EMBRYO OF CAENORHABDITIS ELEGANS

    • Kevin McPherson ;
    • Ryan Christensen ;
    • Hari Shroff ;

    THU-769

    TRACKING THE WORM HEAD: EXAMINING THE GENESIS OF BEHAVIOR IN THE DEVELOPING EMBRYO OF CAENORHABDITIS ELEGANS

    Kevin McPherson, Ryan Christensen, Hari Shroff.

    National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD.

    The Caenorhabditis elegans embryo possesses a simple nervous system with high applicability for the in vivo study of neurodevelopment and the appearance of behavior. We are specifically interested in examining the genesis of motor behavior in the embryo. Using dual view inverted selective plane illumination microscopy (diSPIM), we are able to capture high resolution images of the developing embryo quickly and with isotropic resolution, allowing for the tracking of embryonic movement. Using diSPIM, we imaged nematode embryos and tracked head position in late embryogenesis to examine its utility as a readout for embryonic movement and response. We also identified promoters which labeled the ALM and PLM touch-sensitive neurons. The tools and reagents we have worked with should allow for future work examining the development of this circuit and its associated behaviors.

    FRI-767 MULTISENSORY INTEGRATION IN THE DEVELOPING BRAIN OF THE XENOPUS LAEVIS TADPOLE

    • Oscar Carrillo ;
    • Torrey Truszkowsky ;

    FRI-767

    MULTISENSORY INTEGRATION IN THE DEVELOPING BRAIN OF THE XENOPUS LAEVIS TADPOLE

    Oscar Carrillo, Torrey Truszkowsky.

    Brown University, Providence, RI.

    Perception of meaningful experiences requires that we combine multiple sensory modalities through a process called multisensory integration (MSI). Previous work on the mammalian superior colliculus has revealed the phenomenology of MSI, but little is known about the underlying biophysical mechanisms. In the Xenopus laevis tadpole, a homologue of the superior colliculus, the optic tectum, is directly involved in MSI and is an emerging model for the study of MSI. NMDA receptors (NMDARs) can serve as coincidence detectors in neurons allowing for non-linear integration of synaptic input, so we hypothesized that NMDARs may play important roles in mediating single-neuron MSI and, thus, blocking NMDA receptors will stunt MSI in tectal neurons. We also predict that low-intensity multisensory stimuli undergo greater MSI than high-intensity multisensory stimuli. We employed multisensory behavioral experiments and electrophysiological recordings to address these questions. Behavioral results indicate that multisensory stimuli not only result in significantly greater startle responses than unisensory stimuli, but that tadpoles use MSI to a greater extent when both stimuli are low-intensity as compared to one of the stimuli being high-intensity. Electrophysiology results indicate that low-intensity multisensory stimuli have greater signal enhancement (5.57 ±1.01) than high-intensity multisensory stimuli (1.17 ±0.06). Additionally, the low-intensity multisensory stimuli group has greater MSI (3.18 ±0.68) than the NMDA-antagonist group (1.34 ±0.34). These preliminary findings suggest that MSI is more useful for enhancing low-intensity multisensory stimuli and that the NMDA receptor is at least partially involved with MSI on a cellular level

    FRI-855 BDNF PRODOMAIN POLYMORPHISM VAL66MET INDUCES NEURONAL CHANGES

    • Katherine Lopez ;
    • Joanna Giza ;
    • Francis Lee ;
    • Barbara Hempstead ;

    FRI-855

    BDNF PRODOMAIN POLYMORPHISM VAL66MET INDUCES NEURONAL CHANGES

    Katherine Lopez1, Joanna Giza2, Francis Lee2, Barbara Hempstead2.

    1Hunter College, New York, NY, 2Weill Cornell Medical College, Cornell University, New York, NY.

    The brain-derived neurotropic factor (BDNF) is a necessary component for the nervous system development and differentiation. BDNF is synthesized as proBDNF, and the prodomain region is cleaved off in the vesicle or extracellularly by proteases in order to generate mature BDNF. The biological function of the prodomain fragment remains unclear. However, a single nucleotide polymorphism within the prodomain region that leads to a change from the amino acid valine to methionine has been associated with a predisposition to PTSD and other anxiety disorders, suggesting its role in the fear circuitry. Therefore, our goal was to test if the Met prodomain is an active ligand causing morphological changes in the neurons of the ventral CA1 region of the hippocampus, a primary area in this fear circuitry. We specifically focused on dendritic spines, which are sites of synaptic connections between neurons. To determine morphological changes, we are using super resolution microscopy called 3D-SIM (structured illumination microscopy), which gives us the ability to distinguish between types of dendritic spines and their molecular composition following Met and Val prodomain treatments to hippocampal neuronal cells. It was found that both dendritic spine head diameter and density decreased in vivo, and in vitro there was a decrease in overall density. In conclusion, this prodomain area seems to play an active role in inducing morphological changes in the hippocampus. Hopefully, this can lead to designing more appropriate treatments for neuropsychiatric disorders in humans who possess the Met variation in the prodomain.

    THU-838 IMMUNOHISTOCHEMICAL ANALYSIS OF INHIBITING MICROGLIAL ACTIVATION ON SCA1

    • Daniel Svedberg ;
    • Marija Cvetanovic ;

    THU-838

    IMMUNOHISTOCHEMICAL ANALYSIS OF INHIBITING MICROGLIAL ACTIVATION ON SCA1

    Daniel Svedberg, Marija Cvetanovic.

    University of Minnesota-Twin Cities, Minneapolis, MN.

    Spinocerebellar ataxia type-1 (SCA1) is a deadly, dominantly inherited polyglutamine neurodegenerative disease caused by a CAG-repeat tract expansion in the ATAXIN1 gene. SCA1 is characterized by progressive loss of motor coordination and cerebellar neurodegeneration. We have observed neuroinflammation and activation of glial cells early in the disease process, suggesting a close relationship between neuroinflammation and disease pathology. Because glial cells closely regulate neuronal survival, glial cells are an important potential therapeutic target in neurodegenerative diseases. Microglia are a population of immunological glial cells that become activated in response to neurological damage, but whether microglial activation repairs damage or aggravates neurodegeneration remains controversial. Thus, the goal of this study was to analyze the effects of microglial activation on neuronal pathology in SCA1. This was accomplished by analyzing a genetic mouse model of SCA1 combined with genetic manipulations that inhibit the molecular pathway that mediates microglial activation in order to observe SCA1 pathology in the absence of microglial activation. Cerebella from these mice were then analyzed using immunohistochemical staining of astrocytes, microglia, and cerebellar Purkinje neurons. Preliminary data have demonstrated that inhibiting microglial activation reduces microglial activation, astrogliosis, and cerebellar atrophy. These results merit further investigation into potential therapies targeting microglial activation pathways for SCA1 and perhaps other neurodegenerative diseases.

    THU-849 CHANGES IN NEURONAL MORPHOLOGY AND CONNECTIVITY UPON TDP-43 MISREGULATION

    • Gabriela Rodriguez ;
    • Suzanne Paradis ;

    THU-849

    CHANGES IN NEURONAL MORPHOLOGY AND CONNECTIVITY UPON TDP-43 MISREGULATION

    Gabriela Rodriguez1, Suzanne Paradis2.

    1Escuela de Ciencias y TecnologÌa, Universidad Metropolitana, Cupey, PR, 2Brandeis University, Waltham, MA.

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the lower motor neurons of the brain stem and spinal cord as well as the upper motor neurons of the cortex. In the disease state, the lower motor neurons retract from the muscle, ultimately resulting in muscle atrophy and neuronal death. Frontotemporal lobar degeneration (FTLD), another neurodegenerative disease characterized by atrophy of the frontal and temporal cortices, is related to ALS in that they both share a similar cellular pathology. Interestingly, the majority of ALS and FTLD patients present with neuronal aggregations of TDP-43, suggesting that the misregulation of this gene could be one of the main causes of these neurodegenerative diseases. TDP-43 plays several roles throughout the cell, and one of its main features is its ability to bind RNA. Due to this multifunctionality and to the ubiquitous expression of TDP-43, it has been difficult to elucidate which specific cellular processes go wrong in disease states. RNA-binding proteins have been shown to regulate synapses in neurons and mutations so these proteins might affect synapse formation. Taking this information into consideration, we hypothesized that synapse formation in dendrites might be affected by TDP-43 misregulation. To answer this question, we performed synapse assays by quantifying synapse density on 14DIV cortical neurons in which we overexpressed wild-type or mutant TDP-43. Our initial experiments indicate that the overexpression of the wild-type TDP-43 and RNA binding mutation (F147_149L) has no effect on synapse formation in cortical neurons.

    FRI-857 SELF-ADMINISTERED COCAINE INTAKE PROCEEDING BLAST EXPOSURE IN A RAT MODEL OF MTBI

    • Deseree Povijua ;
    • Christopher Olsen ;

    FRI-857

    SELF-ADMINISTERED COCAINE INTAKE PROCEEDING BLAST EXPOSURE IN A RAT MODEL OF MTBI

    Deseree Povijua1, Christopher Olsen2.

    1New Mexico Highlands University, Alcalde, NM, 2Medical College of Wisconsin, Milwaukee, WI.

    Roughly 75% of brain injuries are ruled as mild traumatic brain injuries (mTBI), which are known to cause neuropsychological sequelae and can affect those with substance use disorders (SUD). There is a large clinical population with TBI-SUD comorbidity and little preclinical research on the effects of mTBI on brain function and SUD. Neuroimaging showed microscopic damage in the medial prefrontal cortex (mPFC). The mPFC is significant in regulating drug-seeking behaviors. We hypothesized that animals subject to mTBI will have an increase in drug self-administration (SA) and/or drug-seeking behaviors. Rats were exposed to a 450 kPa pneumatic blast. A composite neuroscore was obtained for each rat to grade post-traumatic gross neurological dysfunction. All rats were subject to a jugular catheterization and series of phases on a fixed ratio-1 that included food SA, cocaine SA of 2 hours for 15 days and 6 hours for the next 10 days, extinction, and cocaine primed-induced reinstatement. All experiments are in progress. We expect blast animals will have an escalated intake of cocaine in the 2- and 6-hour sessions, a higher response during extinction sessions, and a selective increase in active lever pressing following cocaine priming compared to controls. The use of a rat model allowed for controlled conditions to elucidate relationships between mTBI and addictive behavior. Studying and interpreting neuroadaptations induced by mTBI will help aid in the development of therapeutic strategies that treat mTBI patients.

    FRI-850 IDENTIFYING FACTORS INVOLVED IN A MOUSE'S BEHAVIORAL RESPONSE TO A LOOMING VISUAL THREAT

    • Sarah Sam ;
    • Kyu Lee ;
    • Sean McMahon ;
    • Zeynep Turan ;
    • Markus Meister ;

    FRI-850

    IDENTIFYING FACTORS INVOLVED IN A MOUSE'S BEHAVIORAL RESPONSE TO A LOOMING VISUAL THREAT

    Sarah Sam1, Kyu Lee2, Sean McMahon2, Zeynep Turan2, Markus Meister2.

    1Virginia Polytechnic Institute and State University, Blacksburg, VA, 2California Institute of Technology, Pasadena, CA.

    Studying behaviors triggered by visual stimuli in the mouse could provide insight into the role of visual processes in cognition. Previously, the Meister lab discovered that mice exhibit a defensive behavior in response to a looming stimulus. An expanding black disc is shown above a mouse in a rectangular arena. This stimulus, which simulates an approaching aerial predator, elicits 1 of 2 behavioral responses: the mouse either flees the area to a nest or freezes in place. Despite the fact that these are laboratory mice raised in a controlled setting without any predators, they respond robustly to this stimulus, indicating evolutionary significance in these behaviors. Mice may be using a combination of apparent velocity of the looming stimulus and a cognitive map of its surroundings, among other factors, to decide between freezing and fleeing. Identifying the factors that govern this decision making will help understand the underlying neural circuitry involved in this behavior. We find that fleeing occurs most often when there is a nest present. Mice prefer to flee when the stimulus is presented less than 3 feet from the nest. Finally, we will assess whether the mouse is using a cognitive map of its surroundings to make the decision.

    THU-768 TOXICITY SCREEN OF SMALL MOLECULES AFFECTING THE WNT SIGNALING PATHWAY IN NEURAL STEM CELLS

    • Mary Graves ;
    • Joseph Steiner ;
    • Nasir Malik ;

    THU-768

    TOXICITY SCREEN OF SMALL MOLECULES AFFECTING THE WNT SIGNALING PATHWAY IN NEURAL STEM CELLS

    Mary Graves1, Joseph Steiner2, Nasir Malik2.

    1University of California, San Diego, La Jolla, CA, 2National Institute of Neurological Disorders and Stroke, Bethesda, MD.

    Glioblastomas are malignant tumors with a high prevalence for mortality. The basis of this research was to find a therapeutic that inhibits cancerous proliferation in central nervous system cancers such as glioblastoma. The Wnt signaling pathway has been studied because of its effects on stem cell renewal and survival. Wnt-C59 and BML-286 have been previously identified as Wnt pathway inhibitors with toxicity to cancer cells. These 2 compounds and 3 newly synthesized derivatives of them, G-163, G-171 and G-173, were tested on human neuronal stem cells (NSC) via cell culture. Surprisingly, none of these compounds were cytotoxic to NSCs and one, G-163, resulted in increased survival of NSCs. A cellular assay with EdU incorporation was used to determine if this increased survival was the result of enhanced proliferation. From preliminary data assessing proliferation, G-163 treatment did not result in a notable change in proliferation. In conclusion, BML-286, Wnt C-59, and their derivatives are not toxic to human NSCs, and at least one increases NSC survival. Additional studies are underway to better understand the how G-163 leads to increased survival of NSCs, its precise effect on the Wnt signaling pathway, and its potential as a neuroprotective therapeutic.

    THU-854 IDENTIFYING NOVEL MECHANISMS OF ACTION OF ALLOPREGNANOLONE, A NEUROSTEROID

    • Carlos Martinez ;
    • Synthia Mellon ;

    THU-854

    IDENTIFYING NOVEL MECHANISMS OF ACTION OF ALLOPREGNANOLONE, A NEUROSTEROID

    Carlos Martinez1, Synthia Mellon2.

    1University of California, Berkeley, Berkeley, CA, 2University of California, San Francisco, San Francisco, CA.

    Allopregnanolone (ALLO), a neurosteroid derived from progesterone, is a naturally-occurring anxiolytic and anticonvulsant compound that activates GABAA receptors. ALLO also affects neuronal proliferation and inflammation, suggesting that ALLO may activate additional receptors. We hypothesize that ALLO may activate the G-protein coupled receptor, TGR5, since ALLO’s structure is similar to lithocholic acid (LCA), a TGR5 ligand. We used mouse enteroendocrine STC1 cells to determine if ALLO could mimic LCA’s actions at TGR5 by assessing calcium uptake and glucagon-like-peptide-1 (GLP-1) secretion. Immunocytochemistry demonstrated the presence of the TGR5 receptor in STC1 cells. To study intracellular events triggered by TGR5 activation, STC1 cells were loaded with Fura-2, a calcium indicator. While both 30 µM LCA or ALLO caused similar increases in Fura-2 fluorescence (i.e.,increased intracellular calcium), dose-dependent effects were inconclusive. TGR5-stimulation of STC1 cells also causes secretion of GLP-1, measured by ELISA. Stimulation of STC1 cells with 30 µM LCA or ALLO increased GLP-1 secretion, but effects were not dose-dependent. Our results demonstrate that STC1 cells express the TGR5 receptor, whose stimulation by LCA or ALLO increases calcium entry and GLP-1 secretion, but the dose-dependent effect of either compound was not ascertained. Future studies will determine maximally effective doses of both LCA and ALLO, and will indicate whether ALLO may be another natural ligand for the TGR5 receptor.

    FRI-769 CELL-SPECIFIC EXPRESSION OF CNTNAP2, AN AUTISM SUSCEPTIBILITY GENE, WITHIN THE MOUSE BRAIN

    • Swasty Chandra ;
    • Maria Lazaro ;
    • Olga Penagarikano ;
    • Hongmei Dong ;
    • Daniel Geschwind ;

    FRI-769

    CELL-SPECIFIC EXPRESSION OF CNTNAP2, AN AUTISM SUSCEPTIBILITY GENE, WITHIN THE MOUSE BRAIN

    Swasty Chandra, Maria Lazaro, Olga Penagarikano, Hongmei Dong, Daniel Geschwind.

    University of California, Los Angeles, Los Angeles, CA.

    Autism spectrum disorder (ASD) is characterized by deficits in social behavior, language impairments, and restrictive/repetitive behaviors. Although ASD affects 1 in 68 individuals, there is yet to be a cure that alleviates all of the behavioral symptoms. We know there are hundreds of autism susceptibility genes and mutations that play a role in ASD etiology. Loss of function mutations in our particular gene of interest, CNTNAP2, which encodes for contactin-associated protein-like 2 (CASPR2), cause cortical dysplasia-focal epilepsy syndrome (CDFE), which is highly comorbid with autism. Caspr2 colocalizes with Kv1.2 channels in the juxtaparanodes of axons and mediates neuron-glia interactions, yet not much is known about its cell-specific function. Our current objective is to understand the cellular and molecular mechanisms by which impaired Cntnap2 function leads to ASD-related behaviors. Recent data from our work in the Cntnap2 knock-out mouse, which models ASD, suggests that Cntnap2 is involved in modulation of distinct neurotransmitter systems and suggest Caspr2 could play cell-specific roles. In this study, we use Cntnap2tLacZ/tLacZ mice and beta-galactosidase immunohistochemistry to identify Caspr2 expression in mouse brain tissue. We performed co-labeling of beta-galactosidase with various neuronal markers to identify cell types that express Cntnap2. Data obtained thus far shows that Cntnap2 does show co-expression with parvalbumin, arginine vasopressin, and oxytocin. By observing the expression of Cntnap2, we can determine whether it has a universal function throughout the brain or specific roles pertaining to the individual cell types in which they are expressed.

    THU-847 OPTOGENETIC STIMULATION OF SPECIFIC EXCITATORY AFFERENTS TO DOPAMINERGIC NEURONS INDUCES CONDITIONED PLACE PREFERENCE

    • Megan Aumann ;
    • Alyssa Petko ;
    • Amanda Sharpe ;
    • Michael Beckstead ;
    • Carlos Paladini ;

    THU-847

    OPTOGENETIC STIMULATION OF SPECIFIC EXCITATORY AFFERENTS TO DOPAMINERGIC NEURONS INDUCES CONDITIONED PLACE PREFERENCE

    Megan Aumann1, Alyssa Petko1, Amanda Sharpe2, Michael Beckstead3, Carlos Paladini1.

    1The University of Texas at San Antonio, San Antonio, TX, 2University of the Incarnate Word, San Antonio, TX, 3The University of Texas Health Science Center, San Antonio, San Antonio, TX.

    Midbrain dopamine (DA) neurons will fire a burst of action potentials in response to reward-related stimuli. Glutamatergic afferents are critical in regulating DA neuron-firing patterns, and 2 of the largest glutamatergic inputs to DA neurons are the subthalamic nucleus (STN) and pedunculopontine nucleus (PPN). Lesion and drug administration studies have suggested that these nuclei are involved in various reinforcement processes; however, the necessity of these glutamatergic inputs in driving reward-related behavior is not yet known. In this study, we have examined the causal role of release from these glutamatergic afferents by using an unbiased conditioned place preference paradigm. STN and PPN cell bodies in the mouse were first virally infected with the light-activated protein, channelrhodopsin, and positioned with chronic optical fiber implants. Mice were placed in the chamber for 6 days, 3 days for each side with photo-stimulation paired on one side. On the 7th day, mice were checked for preference for either the control side or the side paired with photo-stimulation. Our results show that mice associate the effects of laser stimulation with their environment and subsequently display a preference for STN and PPN activation. This suggests that STN and PPN collectively are important in regulating reward and reinforcement behavior. [The National Institute of Mental Health (MH079276), National Institute on Drug Abuse (DA030530), and National Institute of General Medical Science/MBRS-RISE (GM60655) supported this work.]

    FRI-847 REGULATION OF ADULT HIPPOCAMPAL NEUROGENESIS BY HYPOXIA INDUCIBLE FACTOR 1α

    • Lauren Carrica ;
    • Lee Anna Cunningham ;
    • Lu Li ;

    FRI-847

    REGULATION OF ADULT HIPPOCAMPAL NEUROGENESIS BY HYPOXIA INDUCIBLE FACTOR 1α

    Lauren Carrica, Lee Anna Cunningham, Lu Li.

    The University of New Mexico, Albuquerque, NM.

    Adult hippocampal neurogenesis from neural stem and progenitor cells (NSPCs) is a unique form of adult brain plasticity linked to learning and memory. Previous studies by our lab have demonstrated constitutive expression of hypoxia inducible factor 1α (HIF1α) within NSPCs of the hippocampal subgranular zone (SGZ) of adult mice. Here, we investigated the hypothesis that HIF1α performs a vital role in adult hippocampal neurogenesis and performance on a neurogenesis-dependent learning task. We utilized a tamoxifen-inducible Cre-loxP approach to selectively delete exon 2 of the Hif1α gene within NSPCs from adult nestin-CreERT2/R26R-YFP/ Hif1α fl/fl triple transgenic mice. The inactivation of HIF1α within NSPCs resulted in a 70% reduction in the number of YFP+ dentate granule cells (DGCs) as well as a 30% reduction in number of YFP+ cells that were also NeuN+ compared to control nestin-CreERT2/R26R-YFP/ Hif1α wt/wt mice (p < 0.05, n = 5 mice/group) 45 days following tamoxifen administration. To determine whether the impaired neurogenesis following Hif1α gene deletion is associated with impaired performance on a neurogenesis-dependent learning task, we tested mice on an A-B context discrimination fear conditioning learning paradigm. This task requires the formation of associations between distinct environmental contexts and an aversive stimulus. Behavioral analysis demonstrated a significant impairment of learning in nestin-CreERT2/R26R-YFP/ Hif1α fl/fl compared to nestin-CreERT2/R26R-YFP/ Hif1α wt/wt mice at 45 days post tamoxifen exposure (p < 0.05) at days 5 and 6 of training, followed by a recovery of performance on day 7 (n = 3 - 7 per group). Currently we are investigating whether HIF1α also influences angiogenesis within the adult hippocampus, which could promote neurogenesis.

    THU-836 ELUCIDATING THE CONTRIBUTION OF NEGATIVE REGULATORY NLRS IN TRAUMATIC BRAIN INJURY

    • Armand Meza ;
    • Irving Allen ;

    THU-836

    ELUCIDATING THE CONTRIBUTION OF NEGATIVE REGULATORY NLRS IN TRAUMATIC BRAIN INJURY

    Armand Meza, Irving Allen.

    Virginia Polytechnic Institute and State University, Blacksburg, VA.

    Traumatic Brain Injury (TBI) has seen increased awareness, particularly in the context of sports. Mechanical trauma to the central nervous system results in the disruption of cellular microenvironments and induces a progressive cascade of secondary events, including inflammation. NOD-like receptors, a family of proteins associated with the immune system, have been shown to influence the rate and amount of inflammation triggered by the immune response following TBI. A unique protein of this family, NLRX1, was recently identified and found to negatively regulate inflammation. The purpose of the present study is to investigate the role of NLRX1 in TBI-induced damage. We sought to evaluate the effects of NLRX1 gene deletion on cortical tissue loss in a murine model of controlled cortical impact (CCI) injury. NLRX1 knock-out mice exhibited larger brain lesions following CCI injury, thus NLRX1 can be concluded to have a role in protecting against TBI. Current and future studies will aim to evaluate the mechanism associated with NLRX1’s attenuation of pathogenesis though 4 possible signaling networks: type-1 interferon, reactive oxidation species, NF-kB signaling, and autophagy. Understanding networks that lead to inflammation will be crucial to treating TBI, and understanding NLRX1 may result in novel therapeutic strategies for TBI patients.

    FRI-836 CHANGES IN INTRINSIC FUNCTIONAL BRAIN NETWORKS ASSOCIATED WITH THE PRESENCE OF PSYCHOPATHY

    • Daisy Reyes ;
    • Vince D. Calhoun ;
    • Kent Kiehl ;

    FRI-836

    CHANGES IN INTRINSIC FUNCTIONAL BRAIN NETWORKS ASSOCIATED WITH THE PRESENCE OF PSYCHOPATHY

    Daisy Reyes1, Vince D. Calhoun2, Kent Kiehl, PhD2.

    1The University of New Mexico, Albuquerque, Albuquerque, NM, 2The University of New Mexico, The Mind Research Network, Albuquerque, NM.

    Psychopathy is a personality disorder associated with lack of conscience, impulsivity, and empathy. Research suggests psychopathy is also related to abnormalities in paralimbic connectivity. However, there has not been enough research on how cerebral intrinsic networks (INs) in general change with the presence of psychopathy. In this study, we hypothesize that there will be changes in the connections between INs in relation to psychopathy. Our research consists of one of the largest ICA analyses of fMRI data collected from nearly1,000 subjects. We studied only male adults ranging from ages 19 to 63 who are either healthy controls or incarcerated individuals with psychopathy. Each subject with psychopathy was given a psychopathy checklist-revised (PCL-R) score representing the severity of this disorder. Group independent component analysis (GICA) was used to analyze resting state fMRI data and to identify INs. We then measured the connectivity among identified INs, the measurement otherwise known as functional network connectivity (FNC). This study is still in progress; however, initial results suggest significant differences in connectivity in psychopathy vs. control between temporal gyrus and basal caudate nucleus INs, the supplementary motor area (SMA) and precuneus INs, as well as SMA and cuneus INs. Our initial results indicate that the connectivity of SMA with the visual cortex and the caudate nucleus is somehow related to psychopathy, something that has not been observed before. Our goal is that, by identifying these INs and the changes influenced by this disorder, we will be able to better understand and characterize psychopathy