1. Prachi Srivastava
Chronic Corticosterone Shifts Effort-Related Choice Behavior in Y-Maze
In these experiments, our objective is to characterize effort-related choice tasks using chronic stressors in mice. We chose to use a chemical called corticosterone (CORT) to model stress induced mood disorders such as major depressive disorder and chronic stress. Accumulated studies have indicated that repeated CORT injections induce depressive behavioral and neurochemical manifestations in rodents. This is because CORT is the stress hormone analog of cortisol in humans and is the major output of the hypothalamus-pituitary-adrenal (HPA) axis, which is hyperactive in both humans with major depressive disorder, and in rodent models of chronic stress. Therefore, we concluded that chronic CORT is a well-validated model of depression. Effort-related choice tasks have been characterized using stressors in rats but the stressors have not been chronic and these have not been characterized in mice. For researchers conducting antidepressant treatment experiments using mice, the results of this experiment would be a better foundation for their research. Adult male mice were administered either Vehicle or CORT in their drinking water for 4 weeks, and continuing throughout all experiments (15 weeks total), and then were tested in a Y-Maze barrier task. Chronic CORT reduced the high reward (HR) arm choice in the Y-Maze when more effort was required to obtain the 4 food pellets (15 cm barrier in the HR arm, p < 0.001; 20 cm barrier in HR arm, p < 0.001) and shifted choice to the LR arm where only 2 pellets were available for consumption. Chronic CORT shifts effort-related choice behavior in the Y-maze barrier task. Taken together, chronic CORT may reduce motivation to work for and obtain a highly rewarding reinforcer when a lesser reinforcer is available.
2. Tara Shrier
The Deep Dorsal Horn: How Spinal Cord Touch Circuits Shape How We Move
In order to perceive, understand, and react to the world as we do on a regular basis, our nervous systems must be able to detect, integrate, and communicate an enormous variety of physical sensations to the brain. For this reason, proper characterization of sensory pathways is of enormous neurological importance. While fairly developed models exist for senses such as hearing and vision, one sense that is still being explored is touch. Our lab studies the neuronal circuitry of the spinal cord deep dorsal horn (laminae IV-V), which is likely important for the integration of touch and proprioceptive information for coordinating motor output. Understanding of this circuit would shed light on the role of innocuous touch sensation in perceiving and responding to our environment, and thus has potential application in treatment of spinal cord injury, when this touch circuit is perturbed.
Using mouse intersectional genetics, our lab has isolated a population of PV (parvabumin+) interneurons that specifically inhabit the deep dorsal horn- at this crucial hub between dorsal sensory input and ventral motor output. Because of their advantageous location, this population is likely important to the sensorimotor circuit, and potentially an important therapeutic target for restoring motor function after injury.
Digital morphological analysis of these neurons revealed a cell profile equipped to handle robust integration of diverse sensory inputs: with large somas, complex neurite branching, and plentiful dendritic spines. Their morphology varies slightly along the rostrocaudal axis, being slightly more complex at spinal segments that innervate the limbs (cervical, lumbar). Polar histogram analysis indicated that dPV neurons extend their branches in many directions, including into dorsal laminae for touch and proprioception (III-VI) which are vital to proper gait coordination. Immunostaining of inputs to PV-IZ revealed that this population receives a significant amount of input from LTMRs and proprioceptors, again supporting their role as local integrators of tactile input for locomotive coordination. Genetic labelling has also revealed subsets of these neurons that are midline crossing and propriospinal, which points to a role in bilateral coordination and integration across multiple body segments.
Finally, experiments using ablation of these neurons are in progress to gauge the role of dPV neurons in motor behavior and functional recovery after injury. If loss of this population causes motor deficits and/or impaired motor recovery, this would further identify them as an important therapeutic target for motor disorders.
3. Nazar Soroka, Jeet Parekh and Samuel Weinglass WITHDRAWN
Effects of Lithium Treatment in-Utero in Down Syndrome Mice
Down Syndrome (Trisomy 21) is a genetic disorder resulting from a triplication of the 21st chromosome in humans. It is commonly characterized by intellectual disability, reduced immunity, congenital heart disease, and infertility. Pregnant mice were given 0.2% lithium chow during the second trimester, and its effects on offspring immunity and infertility was studied. We believe that lithium inhibits Glycogen Synthase Kinase 3 Beta (GSK-3β), an inhibitor of NFAT and WNT/β-catenin, mitigating the immunodeficiency. This was studied via. flow cytometric analysis of pan T and B cells (CD3+ and CD19+) in the whole blood of Ts65Dn mice, a mouse model of down syndrome. We also expect lithium to have a rescuing effect on the litter size of Ts65Dn mice, who generally have a smaller litter compared to wild type C57BL-6J mice. Our results show that lithium increases T-cell percentages (CD3+/CD45+) and decreases B-cell percentages (CD19+/CD45+). Furthermore, we conducted urine analysis on mice for white blood cells (WBC), which would be indicative of a urinary tract infection (UTI). It was concluded that there was no evidence that suggests DS mice are at a higher risk of contracting a UTI. These preliminary results show that lithium treatment may be a promising in-utero treatment for Down Syndrome.
4. Ria Soni
Optogenetics and Antidepressants: Illuminating the Circuitry Behind Depression
Optogenetics is a temporally and spatially precise method by which we can stimulate specific brain areas or projections. Production of light-activated or inactivated channels can be induced in neurons via viral gene expression. This research aims to investigate the neural circuitry behind depression and ultimately delves into the effects of SSRIs (Serotonin-Reuptake Inhibitors) on depression’s pathway through the brain using optogenetics. The accuracy and effectiveness of the optogenetic techniques used is first confirmed by replicating previous behavioral and molecular results from a verified expert on optogenetics. We then delve into an investigation of hippocampal projections involved in anxiety and depressive-like symptoms in a mouse model of depression and antidepressant use. This study hopes to summarize the effects of inhibiting and stimulating a large number of efferent hippocampal projections.
5. Richard Cliver
Microfluidics to Evaluate Glial-Mediated Therapies in the Nervous System
Introduction: Müller Glia cells (MG) across the nervous system (NS) are renowned for their abilities to maintain homeostasis and support neuronal health and aid neurotransmission. Contemporary cell replacement strategies have begun to investigate glial transplantation as a strategy to harness the intrinsic reparative properties of glia to treat vision loss. Surgical insertion of glia into the NS requires both an environment that supports their survival and signals that facilitate their movement to damaged sites. Cerebrospinal fluid (CSF) bathes the brain and spinal cord and nourishes neurons and glia with essential ionic and biomolecular compounds. In addition, injury ligands are well-known to act as chemotactic agents to cause cell movement to damaged areas. This project examined the survival, adhesion and migration of MG in clinically used CSF solutions towards BDNF, a biochemical factor expressed by damaged neurons and well-known to stimulate regeneration. Experiments examined both the utility of CSF mimics in transplantation and the chemotaxis of glia to controlled biochemical signaling.
Materials and Methods: Soft lithography was used to generate polydimethylsiloxane (PDMS)-based microfluidic devices. Müller Glia Cell Line (rMC-1) were seeded in separate microfluidic devices of media (Elliot’s B® 25%,50%,75%,100%, DMEM, 1% FBS, 1% Penicillin-Streptomycin) and Brain Derived Neurotrophic Factor (BDNF) was diffused to establish a gradient promoting migration.
Results and Discussion: Morphology of rMC-1 decreased past the control in Elliott’s B® 25%, 50%, and 75% Solutions.
Figure 1: Morphology of MG. A) rMC-1 Morphology in T-25 Flasks in Elliott’s B® Solutions. (B) rMC-1 in T-25 Flask in 75% Elliott’s B® Solution (1% FBS) at 24 hours.
Conclusion: MG exhibits constant viability in increasing DNF concentration gradients. S42 also survive, adhere, and proliferate in vitro in the Elliot’s B® Solution. It has been found that the cells can exist in vitro in 100% Elliot’s B® Solution (DMEM, 10% FBS) verifying the cells can be transplanted in the clinical cerebrospinal fluid mimic.
6. Estabillo, Benjamin - Truong, Huy - Atieh, Tariq - Cliver, Richard
bme45@scarletmail.rutgers.edu, hdt11@scarletmail.rutgers.edu, tba24@scarletmail.rutgers.edu, rnc54@scarletmail.rutgers.edu
Inhibition vs. Excitation in Network Models of Pain Syndromes
Introduction: Roughly a third of Americans live with some form of chronic pain. The underlying cause of pain syndromes is unknown, but has been theorized to be associated with the self-excitation of neurons. Computational network models of neurons have been used for research in the past, but currently no model exists that studies the effect that inhibitory neurons have on self-excitation of the network. This project has developed a MATLAB generated user interface (GUI) to create a network of neurons in the form of a node distribution graph. Users can define the number of nodes in the system as well as the average length of connection between individual nodes. A corresponding voltage graph is also created. The model allows users to select individual neurons to excite or inhibit, and the voltage graph permits for observation of the effect that inhibition has on the propagation of an action potential in the context of self-excitation.
Methods: The voltage graphs are generated with the FitzHugh-Nagumo model, which is a variant of the Hodgkin-Huxley model. The node distribution graph is based on the Barabasí-Albert model. Verification of the computational model was performed by culturing B35 rat neuroblastoma cells.
Results and Discussion: The model is capable of creating a node distribution graph that very closely approximates the ultra small world model detailed by Barabasí-Albert. A circle-fit algorithm was used to compare the computational model to the cell culture data with respect to cell density.
7. Alfonso Roque
alfonso.roque13@gmail.com
The CELF RNA Binding Proteins Involved in Neocortical Synaptogenesis
Initial synapses within a prenatal neocortex are required for proper establishment of complex functions of the mature neocortex. However, very little is known about the molecular mechanisms behind prenatal synaptic development. Based on preliminary results, I hypothesized that a specific RNA binding protein (RBP) from the RBP family of CELFs (CUGBP, ELAV-like Family), specifically family member 4 (Celf4) plays a key role in the development of these primary synapses in the subplate zone, one of two known locations of initial neocortical synaptogenesis. Our first step was to discover what Celf4 targets through the use of conditional knockout (cKO) mice. After RNA sequencing I found that the cKO when compared to the wildtype (WT) showed a significant upregulation of inhibitory mRNAs (e.g. Gababr2). To observe and evaluate this relationship with inhibitory mRNAs I was tasked with measuring the fluorescence of each immunostain via ImageJ. Following several attempts of developing a proper protocol the process did not produce significant data. Thus, I switched to the quantification and statistical comparison of the cKO and WT in their expression of DAPI (Nucleic) and Gephyrin (GABAergic) markers and found a significant difference between the two conditions. Therefore, developing my hypothesis that Celf4 regulates development of GABAergic synapses. There is still more to discover such as when this effect takes place but as a whole, our research hopes to improve the current understanding of neurodevelopment and provide knowledge that may be used in improving therapeutic methods for treating neurodevelopmental disorders.
8. Sandra Ashamalla
Assessing Reliability in Chronic Stress Models of Depression
Some mood disorders, such as major depressive disorder, are more prevalent in women than in men. However, historically, preclinical studies in rodents have a lower inclusion rate of females than males, possibly due to the fact that behavior can be affected by the estrous cycle. Several studies have demonstrated that chronic antidepressant treatment can decrease anxiety-associated behaviors and increase adult hippocampal neurogenesis in male rodents. Very few studies have looked at the effects of antidepressants on behavior and neurogenesis across the estrous cycle in naturally cycling female rodents. Here we analyze the effects of chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) on behavior and adult hippocampal neurogenesis in naturally cycling C57BL/6J females across all four phases of the estrous cycle. In naturally cycling C57BL/6J females, fluoxetine decreases negative valence behaviors associated with anxiety in the elevated plus maze and novelty suppressed feeding task, reduces immobility time in forced swim test, and increases adult hippocampal neurogenesis. Interestingly, the effects of fluoxetine on several negative valence behavior and adult hippocampal neurogenesis measures were mainly found within the estrus and diestrus phases of the estrous cycle. Taken together these data are the first to illustrate the effects of fluoxetine on behavior and adult hippocampal neurogenesis across all four phases of the estrous cycle. This research will help compare the behavioral and neurological effects of fluoxetine treatment in female mice in comparison to males. In addition, it will determine any possible behavioral or molecular difference in females between phases of the estrous cycle.
9. Namarata Battula
Developing a zebrafish model of CMD caused by POMT1 mutations
Congenital Muscular Dystrophy (CMD) refers to a group of muscular dystrophies present at or near birth. POMT1 mutations in humans cause the most severe form of CMD with muscular dystrophy and malformations throughout the brain, the retina and the anterior chamber of the eye (lens and pupil). In the Manzini Research lab, the goal of my project is to develop a zebrafish model of CMD caused by POMT1 mutations. Studying pomt1-deficient embryos from these fish, I will be able to understand how a mutation in pomt1 can impact protein function, and how this, in turn, can cause CMD. This research will help develop a scientific understanding of the molecular basis of CMD in the zebrafish model, which can be used to develop new drug therapies that will be successful in treating patients with CMD. I will use heterozygous fish carrying a frameshift mutation in pomt1 available in the lab and breed them to generate mutants (knock-outs lacking pomt1 that can be analyzed for muscle, brain, and eye defects). I will first analyze how the mutations affect different tissues of the zebrafish body. Last semester we obtained the pomt1 zebrafish line and, under the guidance of Dr. M.Chiara Manzini, I was introduced to the procedures that I will use to research POMT1 mutations, including cryosection and immunohistochemistry. By practicing these methods, I have laid the foundation to raise and genotype the mutant pomt1 fish for analysis.
10. Wamia Siddiqui
Effects of Dauer on C. elegans Behaviors: Assessing Impact of Various Induction Methods Across Mutants
C. elegans are a microscopic nematode ubiquitously utilized as a model organism in neuroscience research, in part due to their simple nervous systems and stereotypic behaviors. Scientists can use simple organisms like C. elegans to better understand human neurological diseases. This research is focused on dauer in C. elegans, a diapause-like developmental stage that deviates from the standard life cycle. C. elegans go into dauer in response to stressful situations such as starvation, uninhabitable temperatures, or overpopulation. Similar to hibernation, dauer is a stage in which the animal forms a hard cuticle around its body and “shuts off” to exert no energy as a means to maintain itself until conditions are once again favorable. This research explores different methods of inducing dauer in various C. elegans mutants with the aim of comparing how certain behavioral traits may be affected in the post-dauer adult worms. The research measured locomotion, pharyngeal pumping/feeding habits, and response to physical stimuli to better understand how the process of going into dauer, and recovery from dauer, impacts the behavioral patterns of the adult worm.
11. Ozsen, Elif
The Role of Par3 in Dendritic Spine Morphogenesis In Vivo
Partitioning defective (Par) proteins are a family of polarity proteins that play a crucial role in cell polarization and the morphology of a variety of cells, including neurons (Zhang, 2016). Neurons have small, highly polarized protrusions, called dendritic spines. Par proteins may be important in establishing the polarity and morphogenesis of dendritic spines. Normal dendritic spine development is important for properly receiving information from other neurons. Silencing Par3, a scaffolding Par protein, in vivo may elucidate the role of Par3 in normal dendritic spine structural development and cognitive function. We hypothesize silencing Par 3 in vivo will cause abnormal dendritic spine morphogenesis, resulting in decreased spatial recognition and memory, as well as immature structural morphogenesis of dendritic spines in neuronal cells.
The Morris Water Maze (MWM) is currently being used to test spatial learning and memory, while Golgi-Cox staining is being used to determine dendritic spine morphogenesis. However, increased sample sizes must be examined to reach a full conclusion about the effects of silencing Par3 has on spatial learning and memory. Additionally, dendritic spine density and morphology still needs to be analyzed to determine any significant differences and conclusions about the morphogenesis
Overall, the results from the following research can give us insight as to how silencing Par3 may play a role in the morphology and function of dendritic spines. Abnormalities in the structure of dendritic spines and neurons caused by silencing Par3 may also provide insight for a variety of neuropathological disorders in humans, such as Autism Spectrum Disorder, Alzheimer’s Disease, and Schizophrenia.
12. Sullivan, Dylan
Electrophysiological changes in sensory encoding reflect experience-dependent plasticity specific to opioid and cocaine-associated cues
Drug abuse is a pervasive problem for society, and it is important to understand how it changes the physiology of the body and brain. This experiment investigates plasticity in the sensory brain that is driven by exposure to drug (morphine or cocaine) and auditory cues. If there is experience-dependent plasticity in the early auditory processing of drug-associated cues, then part of the etiology of drug addiction may be related to the effects of these drugs on sensory systems. To investigate this hypothesis, subjects were split into three groups that all received a tone paired with saline, and another tone paired with treatment (saline, morphine, or cocaine). Drug-dependent effects were compared within subjects to control tone (saline), and across subjects to control group (saline only group) to determine if morphine or cocaine have any lasting effects on sensory processing. Subjects were given two sessions per day for two weeks to establish an association between the tone and treatment, and auditory brainstem responses (ABR) were recorded before, during, and after cue-association. To analyze changes in ABR waveforms, we measured latency and amplitude across treatments for each peak (I-V). Neurophysiological findings revealed a significant increase in latency for ABR Peak I in the morphine-treated animals for the morphine-paired tone. Analysis of broadband clicks (control sound stimulus) showed a significant increase in Peak I latency for cocaine-treated animals and a significant difference between all three groups. Peak II showed a significant difference between the two drug groups. The findings support the idea that drugs of abuse have both global effects on sensory processing and specific effects on the processing of drug cues, and the effects are unique to different categories of drugs. These data offer an interesting insight about the effects of drugs on long-term sensory plasticity and cued behavior that warrant further research.
13. Yecham, Pavankumar
Scalable Optogenetic Modulation of Pain: A Novel Implant for Nociceptive Stimulation of the Sciatic Nerve
The number of Americans that currently live with chronic pain is estimated to be greater than 30% of the entire population (Volkow & McLellan, 2016). The development of chronic pain is known to play a role in increasing the risk for substance use disorders, anxiety, and depression (Tetsunaga 2018). Knowing this, it is imperative to elucidate the changes that occur in the brain as pain transitions from acute to chronic, how the intensity of pain affects neuronal plasticity, and how areas of the brain that control positive and negative outcomes as well as emotion and mood are affected by chronic pain. To help answer this question, we have created a novel, implantable nerve cuff capable of producing a range of pain intensities when combined with optogenetic technologies. Further we have validated the utility of this nerve cuff by optogenetically stimulating peripheral pain sensing neurons (i.e., nociceptors) following an injection of the light-sensitive protein channelrhodopsin into the sciatic nerve. We predict that future in vivo testing will demonstrate the scalable delivery of nociceptive stimuli and hope that this device can be used in future studies examining the transition from acute to chronic pain.
14. Bazer, Allyson
The Effect of Chemogenetic DREADD Manipulation in the Ventral Dentate Gyrus of Chronically Stressed Females on the Behavioral Antidepressant Response
Major Depressive Disorder is a psychiatric disorder that affects millions, with only 1 out of 3 patients attaining remission after treatment with a selective serotonin reuptake inhibitor. 5-HT1A receptors (a Gi-coupled inhibitory receptor) on mature granule cells in the dentate gyrus are necessary for the behavioral effects of antidepressant treatment. Because inhibition of DG GCs is necessary for the response to antidepressant treatment, we assessed whether direct inhibition of GCs in the ventral DG mimicked antidepressant treatment. We show that Gi-DREADD-mediated inhibition of the ventral DG results in a decrease in negative valence behaviors, like what is seen after chronic antidepressant treatment. We also assessed whether direct inhibition or stimulation of GCs in the ventral DG could alter response to antidepressant treatment. We show that Gi-DREADD-mediated inhibition of the ventral DG results in the conversion of non-responders to fluoxetine (an antidepressant; FLX) treatment into responders, while Gq-DREADD-mediated stimulation results in conversion the of responders to FLX treatment into non-responders. Taken together, these data suggest that inhibition in the ventral DG is necessary for the antidepressant response and illustrate that it is possible to bidirectionally alter the behavioral response to FLX treatment.
15. Narvaez, Samantha
A model of fever-induced seizures in the African naked mole-rat
A common cause of childhood hospitalization is fever-induced (febrile) seizures. Children that experience a fever can demonstrate an epileptic seizure due to overexcitation of the brain. If the seizure persists, the chances of developing a lifelong epilepsy disorder increases significantly. There is no common treatment to prevent febrile seizures or their consequences, partially because there are no animal models that demonstrate seizure in response to fever.
Poly (I:C) is a synthetic RNA molecule that induces an immune response due to its similar pattern with a viral infection. We used Poly (I:C) to induce a fever in African naked mole-rats (NM-R) in order to produce a febrile seizure. Following a dose of 10mg/kg Poly (I:C), NM-R go through a pattern of temperature spikes until they reach seizure. The temperature increase and evidence of seizure behavior were recorded.
Due to the unique brain chemistry of NM-R, these animals are very good models for epilepsy and seizure disorders. While other rodent models have been established for febrile seizures, NM-R pose two specific advantages: 1) their life-long alteration in GABA function that mimics GABA function in children, and 2) their mutation of the neuronal potassium chloride cotransporter 2 (KCC2), which is a risk factor for febrile seizures in humans.
Close monitoring of the NM-R post-seizure can determine patterns of seizure behavior not associated with a fever, and possibly offer insight into the development of epilepsy due to febrile seizures.
16. Pizzano, Carina
The Effect of SYNJ1 in Substance Abuse Phenotypes
The SYNJ1 gene is known to be important for dopamine-related disorders. Additionally, mutations of the SYNJ1 gene have been linked to bipolar disorder, schizophrenia, and Parkinsonism. Accordingly, our preliminary data have demonstrated that SYNJ1 deficient mice (SYNJ1+/-) have impairments in their dopaminergic system and with synaptic recycling. Despite these clear links to midbrain dopamine systems, the effect of SYNJ1 mutations on motivation and drug-seeking behaviors have not been studied. To assess the role of the SYNJ1 gene in reward-seeking behavior, we used male and female SYNJ1 deficient mice (SYNJ1+/-) and littermate controls (SYNJ1+/+) in behavioral tests to assess specific features of motivated behavior. These tests included the Sucrose Preference test, Open Field assay, Elevated Plus Maze assay, Operant Conditioning paradigm, a Progressive Ratio test and a Cocaine Conditioned Place Preference (CPP) paradigm that included a test for drug-primed Reinstatement test. Our results thus far suggest that SYNJ1 deficient males may have deficits in reward learning, as seen in the CPP and Operant Conditioning paradigm. SYNJ1 deficient females do not appear to show these same trends. These preliminary findings indicate that changes in reward processing conferred by SYNJ1 deficits may be critically modulated by sex. Further investigation of motivational deficits and susceptibility to cocaine tolerance and abuse is needed to confer this initial data.
17. Liu, Tonia
Exercise as a Stress-Intervention Method in a Mouse Model of Autism
Autism Spectrum Disorder (ASD) is an extremely prevalent neurodevelopmental disorder that is characterized by challenges with social skills, repetitive behavior, and communication deficits. Individuals with ASD are also more susceptible to stress, and thus high rates of comorbidity exist between ASD and psychological disorders such as depression and anxiety. Past research has shown that mutations in the Engrailed-2 (EN2) gene lead to behavioral and anatomical phenotypes similar to those of people with ASD, allowing us to use mice with the EN2 knock-out (KO) gene as a neurodevelopmental animal model of autism. With this model, we are able to better understand the impact of stress. Previous work in our lab has suggested that EN2 KO mice are more susceptible to stress than their wild-type (WT) counterparts, and subsequently display more anxiety-like and depressive-like behaviors after 10 days of Chronic Social Defeat Stress (CSDS). Our question then becomes: Is there any way to reduce susceptibility to stress in EN2 KO mice? Exercise is known to decrease stress, anxiety, and depression. Thus, the aim of this study is to determine whether exercise has preventative and/or ameliorative effects in populations that are highly susceptible to stress. To better understand the effect of exercise, a traditional CSDS cohort, an exercise and CSDS cohort, and an exercise with no CSDS cohort were run. The behaviors from each cohort were then compared to determine the effect of exercise. Positive results from this study support the role of exercise as a possible intervention approach.
18. Plate, Corey
A Metabolic Switch for Colony Dispersal in the African Naked Mole-Rat
African naked mole-rats are fossorial rodents that spend nearly all of their time in the close quarters of a subterranean nest. Here, they are exposed to carbon dioxide in excess of sixty-six times atmospheric levels. This environment is highly tolerated, but, if exposed to normoxic air, naked mole-rats are prone to seizure — they are well adapted to colonial living, but heavily penalized for venturing from it. Reciprocally, they have derived highly adaptive traits, such as extreme longevity, cancer resistance, and eusociality. However, over time, the cumulative effects of inbreeding could prove deleterious, leaving the species vulnerable to disease, and selecting for undesirable recessive traits. To overcome this, this species has evolved a caste of breeders who, rather than mating or competing with the nascent queen, leave to establish a novel colony. However, in order to fulfill this role, these dispersers must leave the protective carbon dioxide of the nest, and assume a tolerance for normoxic air. This suggests that dispersers and non-dispersers utilize oxygen differently. Non-dispersers have been found to need oxygen less than any phylogenetic relative. Evidence suggests that they rely on substrate level phosphorylation through the catabolism of fructose, rather than oxidative phosphorylation. This may explain their adaptation to hypoxic air, and decreased metabolism, which may help explain their longevity, and low cancer risk. However, a physiological switch must occur for naked mole-rats to change castes. We hypothesize that non-dispersers rely upon substrate level phosphorylation, but that an epigenetic switch can reassign them to oxidative phosphorylation. We hypothesize that this switch is observable as initially low concentrations of GLUT4 in non-dispersers, which increases to expected values in dispersers. ELISA results preliminarily suggest that this is the case in hippocampal tissue, but cardiac muscle is a better target, which we evaluate via Western Blot.
19. Modi, Jil
Relationship between Clathrin and Lysosomes with Variants of RME-8 Protein
A major goal of my research is to determine the relationship between clathrin and lysosomes, and to see if it is altered by mutant alleles of RME-8. RME-8 is a protein that is involved in uncoating clathrin on endosomes in order to maintain separation between the recycling and degradation pathways. In addition to its presence on endosomes, clathrin plays a role in autophagic lysosome reformation (ALR). If RME-8 is knocked down, this could lead to an overaccumulation of clathrin on endosomes resulting in lack of free clathrin to aid in ALR. The goal of determining the relationship between clathrin and lysosomes, as well as how RME-8 might affect it, was not achieved due to the current circumstances, but the project will be continued once lab work resumes. Additionally, I set out to determine the effect that mutant alleles of RME-8 had on lysosome elongation (lysosomes being marked by LMP-1), as well as improve my imaging acquisition skills. While I did see slight elongation of LMP-1 labeled lysosomes in the b1023 rme-8 knock out strain after incubation at the nonpermissive temperature, it was not significant. This may be due to not acquiring enough images. When lab work resumes, I will continue to image WT and b1023 lines to determine if there is a significant difference, as well as image LMP-1 in the Parkinson’s allele background.
20. Cruz, George WITHDRAWN
Title: Influences of Taurine Pharmacodynamics and Sex on Active Avoidance Learning and Memory
Authors: Cruz, G.1,2, Ayaz, Z.1,2, Boby, A.3, Zhu, W.1,4, Cadet, P.1,2 & Neuwirth, L.S.1,5
Presenting Author is Underlined & Bold.
Affiliation & Departments:
1SUNY Neuroscience Research Institute, SUNY Old Westbury, Old Westbury, NY 11568, USA
2Department of Biology, SUNY Old Westbury, Old Westbury, NY 11568, USA
3Department of Biology, New York Institute of Technology, Old Westbury NY 11568, USA
4Department of Biology, Empire College, Old Westbury NY 11568, USA
5Department of Psychology, SUNY Old Westbury, Old Westbury, NY 11568, USA
Taurine has shown promising pharmacotherapeutic effects in alleviating anxiety-like behaviors, improving cognitive outcomes, and providing neuroprotective benefits. Despite promising studies on taurine pharmacotherapeutics characterized across animal models, evaluating the pharmacodynamics of taurine within a single study to better understand how taurine influences neurobiological mechanisms producing such benefits is required. Further, sex as a critical factor, lacks proper examination for improving the fields understanding of taurine’s benefits for potential translational pharmacotherapuetic applications. Thus, the present study sought to examine the effects of taurine at different routes of exposure at the equivalent physiological dosage, to evaluate its influence at different stages of an active avoidance learning and memory task in adult (i.e., PND 55-70) Long Evans Hooded male and female rates. The active avoidance test was comprised of a training session (i.e., 20 trials, a 1 hr test break, followed by another 20 trials), a 24 hr test session, and a 48 hr and 1 week retention session (i.e., all 20 trials). Taurine (2-amino ethane sulfonic acid) was either administered per os chronically at 0.05% in the drinking water (w/v) for 4-weeks prior to testing (i.e., chronic exposure), or was administered as 43 mg/kg i.p. injection (i.e., acute exposure) 15 minutes prior to training (i.e., priming learning acquisition) or prior to the 24 hr test session (i.e., priming learning reconsolidation). The results showed that Control females had increased latencies during training, but decreased during testing when compared to Control males. Alternatively, taurine-treated animals exhibited sex, route of, and exposure time-period-dependent differences in latency, avoidance, escape, and penalty responses across test conditions compared to Control animals. These findings describe a comprehensive evaluation of taurine pharmacodynamic effects (i.e., nootropic and anxiolytic value) as a function of sex and in relation to learning and memory during different time-periods along an adaptive learning continuum.
21. Joseph, Jewel
Title: The Effects of Developmental Lead (Pb2+) Exposure on Later Life Social Behaviors: Implications for Social & Emotional Psychiatric Susceptibilities
Authors: Joseph, J.N.1,2, Cruz, G.1,2, Cabanas, E.1,2, Vasquez, M.A.2,3, Khairi, E.B.1,2, Bonitto, J.R.1,2 & Neuwirth, L.S.2,4
Presenting Author is Underlined & Bold.
Affiliation & Departments:
1 Department of Biology, SUNY Old Westbury, Old Westbury, NY 11568, USA
2 SUNY Neuroscience Research Institute, SUNY Old Westbury, Old Westbury, NY 11568, USA
3 Department of Chemistry & Physics, SUNY Old Westbury, Old Westbury, NY 11568, USA
4Department of Psychology, SUNY Old Westbury, Old Westbury, NY 11568, USA
Lead (Pb2+) is neurotoxicant that causes damage the developing brain resulting in life-long impacts to cognition and behavior. However, less is known regarding Pb2+-influences on social-emotional behavior that are equally important domains of cognitive function, which promote adaptive, procreative, and survivalist outcomes. Here we compared male and female Control Long Evans Hooded rats to characterize the sex-dependent differences in in the Neuwirth-El IdrissiTM Light/Dark Social Interaction Test (LD/SIT). Then we compared the effects of Perinatal to Postnatal Day 22 (PND-22) rats exposed to either 150 ppm or 1,000 ppm Pb2+-acetate in their drinking water, against the male and female control rats. The LD/SIT consisted of a 3-Days (habituation/alone, stranger, and novel toy) series of conditions for 10-minutes under green light (3 Lux). The rats’ frequency, duration, latency to first response, and rate of response per minute were examined for social attempts, socializations, and social avoidances. The results showed that Control female rats showed an increase in the frequency, duration, and response per minute for socializations and social avoidance, as well as, a decrease in the latency to first social avoidance, when compared to Control male rats. In contrast, the male Peri-22 150 ppm rats were no different from Control male rats. However, the Peri-22 1,000 ppm male rats showed an increased duration in their social avoidance when compared to Control male rats. Alternatively, female Peri-22 150 ppm rats showed a decrease in the frequency of social avoidance and rate of socialization and an increase in the duration of social attempts and latency to first socialization when compared to female Control rats. In contrast, the female Peri-22 1,000 ppm rats showed a decrease in the frequency, duration, and rate of social attempts, as well as, an increase in the latency to first social attempt. Taken together, the present study provides the first evidence in the literature that targeted a social-emotional model of childhood Pb2+-poisoning, that showed sex- and dose-dependent effects in which females are more negatively affected than males. These findings provide a unique ability for future neuropsychopharmacological applications for treating social-emotional psychiatric susceptibilities.
22. Kumar, Tania
Hormonal effects on neuroimmune function and glioblastoma survival
Microglia are the resident macrophage-like immune cells of the central nervous system. They can be polarized in a pro- or anti-inflammatory manner, and it has been well established that a predominance of anti-inflammatory microglia promotes the growth and invasion of glioblastoma. Further, it has also been observed that men are not only more likely to be diagnosed with glioblastoma, but are also more likely to die of this disease than women following detection. In this project, we aim to investigate if the reason for this disparity is due to the fact that the polarization state of microglia in men is by default more anti-inflammatory, and also determine if this disparity can be explained by hormonal signaling.
23. TIlton, Peter
The effects of histone deacetylase 3 (HDAC3) inhibition to enhance auditory long-term memory by facilitating temporal coding in the auditory cortex
Peter Tilton, Andrea Shang, MS, Kasia M. Bieszczad, PhD
Long-term memory (LTM) requires gene expression to enable neurophysiological plasticity necessary for its formation. LTM formation can be blocked by histone deacetylases (HDACs) that remove acetyl groups from chromatin, which restricts access to gene expression (Barrett & Wood, 2008). Auditory associative learning can induce sound-specific remodeling in the auditory cortex (Acx) – a neural substrate of auditory LTM. Administration of HDAC3-inhibitor (HDAC3i) enhances auditory cortical neuroplasticity to promote the formation of strong and precise memory for sound (Bieszczad et al., 2015; Shang et al., 2019). Prior studies have focused on neuroplasticity of rate coding in auditory cortex. This project investigates the effects of HDAC3 inhibition on temporal coding as sound-evoked spike latency. Previous studies suggest decreases in first spike latency (FSL) as a potential marker of improved memory (Heil 2004). Thus, we hypothesized that FSL would be decreased more in HDAC3i-treated animals than in VEH animals for the remembered training sounds. For this study, rats were trained to perform an sound-reward associative discrimination (5.0kHz S+, rewarded tone; 11.5kHz S-, unrewarded tone). After reaching performance criterion, evoked responses to tones were recorded in vivo from the auditory cortex. Custom MATLAB scripts were used to analyze sound-specific patterns in FSL. We present differences in FSL plasticity for the S+/S- tones between HDAC3i and VEH animals. From these results, we draw conclusions on the effects of HDAC inhibition on FSL. This work is the first to investigate how temporal coding properties of the auditory system are affected by HDACs to promote LTM.