Behavioral Neurobiology Commons^™

Glutamate, And Its Relationship To Task-Induced Functional Connectivity In The Human Brain: A Focus On Schizophrenia, Kathleen Liu Young, John Kopchick, Jeffrey Stanley, Vaibhav Diwadkar

Medical Student Research Symposium

Glutamate is the brain’s major excitatory neurotransmitter mediating both neuroplasticity and network function (Zhou & Danbolt, 2014). Basal glutamate (Glu) measured using proton magnetic resonance spectroscopy (1H-MRS) provides insight into a region’s density of neuropil related to the glutamatergic system. Moreover, given the role of glutamate in mediating brain network function, Glu levels may play a role in the brain’s functional connectivity (FC), which is typically estimated from functional magnetic resonance imaging (fMRI) time series data. These questions converge when considering the clinical syndrome of schizophrenia (SCZ). Patients with SCZ show abnormalities in basal Glu in the hippocampus and prefrontal …

Glucocorticoid Receptor Dysregulation Underlies 5-Ht2a Receptor-Dependent Synaptic And Behavioral Deficits In A Mouse Neurodevelopmental Disorder Model, Justin M. Saunders

Theses and Dissertations

Schizophrenia is a severe neuropsychiatric disorder that presents with diverse symptoms, some of which remain resistant to treatment. Increased risk of neurodevelopmental disorders such as schizophrenia has been observed following gestational infection in humans, leading to development of maternal immune activation (MIA) animal models. Increased density of the serotonin 5-HT2AR receptor (5-HT2AR), the primary target of hallucinogenic drugs and a key target of atypical antipsychotics, has been observed in postmortem antipsychotic-free prefrontal cortex samples from schizophrenia subjects, a change reflected in frontal cortex of adult MIA offspring. To model MIA, we administered 20 mg/kg i.p. of the viral mimetic poly-(I:C) …

Alcohol Consumption In A Preclinical Model Of Schizophrenia, Liza Hernandez

Electronic Theses and Dissertations

Schizophrenia is a debilitating psychiatric disorder that affects approximately 1% of the global population. Schizophrenia is highly comorbid with other psychiatric disorders such as Alcohol Use Disorder (AUD) with a prevalence rate of 27% - 65%, which is significantly higher than AUD exhibited by the general population (6%). Research indicates that a higher rate of AUD in individuals suffering from schizophrenia may be related to the common neuronal pathways that underlie the expression of both disorders. The present study will determine whether the neonatal quinpirole (NQ) rodent model of schizophrenia will approximate the human condition and exhibit increased EtOH consumption. …

Learning And Motivation For Rewards In Schizophrenia: Implications For Behavioral Rehabilitation, Victoria Martin, Alexandra Brereton, Jicheng Tang

Publications and Research

Purpose of review: Impaired reward processing and amotivation are well documented in schizophrenia. We aim to review the current state of neuroimaging and behavioral research addressing components of motivational deficits in this complex and impairing syndrome. Evidence will be integrated to inform the ongoing development of effective strategies for behavioral rehabilitation. Recent findings: While striatal dopamine and aberrant reward prediction errors have been connected to amotivation in schizophrenia, they are not sufficiently full explanations of reward processing impairments. Frontal dysfunction and associated cognitive control deficits also have evidenced involvement in atypical reward prediction, learning, and valuation. Ongoing work supports the …

The Effects Of Two Novel Anti-Inflammatory Compounds On Prepulse Inhibition And Neural Microglia Cell Activation In A Rodent Model Of Schizophrenia, Heath W. Shelton

Electronic Theses and Dissertations

Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits …

Disc1 Knockout Rats Reveal Sexually Dimorphic Patterns Of Impairment Across Development, Stephanie S. Desrochers

Honors Theses

Schizophrenia is a chronic disorder characterized by three symptom categories: positive (hallucinations, delusions), negative (anhedonia, anxiety), and cognitive (sensory processing and memory deficits). We worked with a biallelic deletion of the Disrupted-in-schizophrenia-1 (DISC1) gene in Sprague-Dawley rats to facilitate our understanding of the biological bases of schizophrenia. Mutations of DISC1 are associated with a higher prevalence of schizophrenia. Adult DISC1 knockout, compared to wildtype, rats display features of schizophrenia-like outcomes in rodent models. The present study investigated the progression of the cognitive symptom deficits in prepulse inhibition (PPI), assessing animals at postnatal days 17 (pre-weaning), 26 (post-weaning), 39 (adolescent), and …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Testing The Efficacy Of Lsn2463359, A Metabotropic Glutamate 5 Receptor Positive Allosteric Modulator, In Animal Models Of Schizophrenia, Dierdre M. Freamon

Seton Hall University Dissertations and Theses (ETDs)

For many years the dominant theory surrounding the cause of schizophrenia was focused on elevated dopamine levels found in critical areas of the brain. Recently a new theory has emerged pointing to elevated glutamate levels resulting from hypofunction of NMDA receptors and hypoactivity of GABAergic neurons which normally inhibit glutamatergic cells in a tonic manner. Therefore, while traditional antipsychotics directly block dopamine receptors, some of the newly generated compounds are designed to modulate glutamate to normal levels.

I propose testing the efficacy of the metabotropic glutamate 5 receptor modulator LSN2463359, previously shown to act as an indirect agonist of the …

Exposure To Kynurenic Acid During Adolescence Increases Sign-Tracking And Impairs Long-Term Potentiation In Adulthood, Nicole E. Deangeli, Travis P. Todd, Stephen E. Chang, Hermes H. Yeh, Pamela W. Yeh, David J. Bucci

Dartmouth Scholarship

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and …

Sex-Specific Brain Deficits In Auditory Processing In An Animal Model Of Cocaine-Related Schizophrenic Disorders, Patricia A. Broderick, Taylor Rosenbaum

Publications and Research

Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. …