Behavioral Neurobiology Commons^™

Investigating The Effects Of Maternal Immune Activation On Sensory Processing: Timing, Immune Mechanisms, And Gene-Environment Interactions, Faraj Haddad

Electronic Thesis and Dissertation Repository

Maternal infection during the first or second trimester of pregnancy poses a risk factor for the child to have neurodevelopmental disorders like autism spectrum disorder (ASD) and schizophrenia. Various clinical and preclinical studies have shown that the maternal immune response to infection, also known as maternal immune activation (MIA), can disrupt fetal brain development.

Over the past two decades, MIA has been studied in rodents using the Polyinosinic Polycytidylic acid (Poly I:C) rodent model. Poly I:C has a molecular pattern resembling viruses that can induce a robust immune response. Following exposure to Poly I:C MIA, rodent offspring exhibit many brain …

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. …

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 …

Cannabinoid Transmission In The Basolateral Amygdala Modulates Prefrontal Cortex And Ventral Hippocampal Activity, Brian J. Pereira

Electronic Thesis and Dissertation Repository

The cannabinoid system is important for maintaining neuron-to-neuron communication within the mammalian brain. One of the most commonly used substances to alter the cannabinoid system is cannabis. Individuals who are exposed to cannabis report having dissociable effects; both positive and negative. High amounts of THC have been commonly associated with the negative effects of cannabis, whereas CBD can be used to counter these. Pre-clinical evidence suggests that the combination of the two compounds can produce a therapeutic benefit for individuals who are susceptible to the effects of THC. The present study investigates whether the combination of THC+CBD can prevent electrophysiological …

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 …

Dissociating The Psychoactive Effects Of Distinct Cannabis Compounds In The Mesocorticolimbic Circuitry, Jordan S. Zunder

Electronic Thesis and Dissertation Repository

The discovery of the endocannabinoid system propelled understanding of the mechanisms of action of cannabinoid compounds. While marijuana is the most widely used illicit substance in the world, the neuropsychopharmacological mechanisms that underlie the diffuse effects of cannabis in the brain remain poorly understood. This is because marijuana smoke represents a complex mixture of chemical components, possessing dissociable psychoactive properties. Clinical evidence suggests a functional dissociation between the two main pharmacological components of cannabis, Δ9- tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Using a combination of cortical microinfusions during two emotional learning paradigms, and single-unit in vivo electrophysiological recording, we investigated the …