Behavioral Neurobiology Commons^™

History-Dependent Gain Control In The Paraventricular Thalamus: Neural Substrates Of Stress-Enhanced Fear Learning, Michael Martino

MUSC Theses and Dissertations

Post-traumatic stress disorder (PTSD) is characterized by hyperarousal and heightened reactivity that generalize beyond the original traumatic event, yet the neural mechanisms by which prior stress experience biases future fear learning remain poorly understood. Stress-enhanced fear learning (SEFL) is a well-validated rodent model of this phenomenon, in which a severe stressor produces persistent sensitization of subsequent fear acquisition. This dissertation used a 30-day SEFL paradigm to identify the brain-wide functional signature of stress sensitization and to identify candidate neural substrates.

Whole-brain cFos mapping during acute fear acquisition revealed a predominant pattern of suppressed neural activity in sensitized animals, with limbic …

Circuit And Synaptic Mechanisms Of Methamphetamine Induced Cognitive Deficits During Abstinence: Roles Of The Perirhinal-Prefrontal Pathway And The Nucleus Reuniens, Sarah Goldsmith

MUSC Theses and Dissertations

Cognitive deficits during abstinence are a hallmark of methamphetamine (meth) use and indicative of negative treatment outcomes. In rats, both long access meth self-administration and meth binge produce recognition memory deficits due to drug-induced plasticity within the perirhinal cortex (PRH). PRH projections are numerous and include the medial prefrontal cortex (mPFC) and the Nucleus Reuniens (NRe). In the first study, the role of the PRH-mPFC reciprocal circuit in novel object recognition memory was investigated by infusing an rgAAV encoding GFP-tagged Cre recombinase into the PRH or the mPFC. Following surgery, rats explored objects. During exploration, PRH neurons receiving input from …

Influences Of Sex, Alcohol, And Stress On Conditioned Fear Responses, Heyam K. Mayberry

MUSC Theses and Dissertations

Learned fear responses are acquired through the identification and association of threatening stimuli with aversive outcomes. Fear responding and the proper maintenance of defensive behaviors is integral to survival. However, without the homeostasis of such systems, fear responses can become maladaptive and lead to dysregulated behavioral responding. Psychological conditions such as alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) often lead to impairments in fear learning, deficits in fear memory, and heightened fear responses. While there are clear sex differences in the prevalence of both AUD and PTSD, development of either disorder increases the risk for comorbid AUD/PTSD, leading …

Neural Correlates Of Socially Rewarding Memories In Posttraumatic Stress Disorder, Kyle P. Blidy

MUSC Theses and Dissertations

Significance. Memory disturbances for emotional content are central to PTSD, yet most research focuses on trauma memories. Recent evidence suggests that enhancing access to positive memories could improve mood, affect regulation, self-esteem, and integration of trauma memories. However, the neurocognitive mechanisms underlying positive memory encoding in PTSD are poorly understood. No study has examined memory for positive social items in PTSD, which is important because PTSD entails social withdrawal and reduced accessibility to positive memory. Additionally, positive memories embedded in a social context have enhanced subjective value and strengthening their accessibility may confer greater benefits to wellbeing compared to non-social …

Prelimbic Neuronal Ensembles In Natural Reward Seeking, Roger Ian Grant

MUSC Theses and Dissertations

External cues can become powerful motivators of behavior when paired with rewarding stimuli, such as natural rewards or drugs of abuse, as is the case in individuals with substance use disorder (SUD). The dorsomedial prefrontal cortex (dmPFC) has been implicated as a neural substrate which encodes cue-reward associations and has been shown to exert top-down control over both natural and drug reward seeking. We and others have shown that activity within the dmPFC is heterogeneous during reward seeking, with some neurons displaying excitatory responses to reward-predictive cues, and others showing inhibitory responses to the same cues. Furthermore, this response heterogeneity …

Activity Dynamics Of The Nucleus Accumbens Neurons During Natural And Drug Reward Seeking, Reda M. Chalhoub

MUSC Theses and Dissertations

The nucleus accumbens core (NAc) represents a major neural substrate of reward encoding that has been found to play a role in differentially regulating natural and drug rewards, including cocaine. Its constituent D1- and D2- receptor expressing medium spiny neurons (MSN) are alternatively hypothesized to have either opposing effects on reward seeking or a shared role in forming encoding “ensembles” – a sparsely activated population of neurons that encode reward associations- that coordinate behavioral responding to rewards and cues predicting reward availability. Previous methods used to study these neuronal populations failed to temporal quantify the cell-type specific activity in reward …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Individual Differences In Cocaine-Conditioned Avoidance Behavior And Implication For Addiction Vulnerability, Maya Eid

MUSC Theses and Dissertations

Decades of studies have examined the mechanisms by which drugs of abuse produce strong rewarding effects that drive addictive behavior. However, these drugs also produce aversive effects that are less well understood, but that also strongly influence drug-seeking, and may contribute to individual variation in addiction liability. For example, individuals with particularly strong aversive responses to nicotine or alcohol may be less likely to acquire smoking or drinking habits, with these protective effects arising from specific biological differences in nicotinic receptor function or alcohol metabolism, respectively. These aversive effects can also be exploited therapeutically, as in widely available treatments for …

Role Of Dynorphin/Kappa Opioid Receptor Activity Within The Extended Amygdala In Binge Alcohol Drinking, Harold Lewis Haun

MUSC Theses and Dissertations

Alcohol Use Disorder (AUD) is a significant national and global public health problem. Of concern, binge drinking is the most common pattern of excessive alcohol consumption and serves as a risk factor for the development of AUD. Recent studies have implicated the dynorphin/kappa opioid receptor (DYN/KOR) neuropeptide system in this pattern of drinking but the precise circuitry mediating these effects are poorly understood. The central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) are two interconnected structures within the extended amygdala macrostructure that are rich in DYN/KOR and thought to contribute to binge drinking behavior. In the present …

Effects Of The Abused Inhalant Toluene On Mpfc-Dependent Cognitive Behaviors And Associated Neural Activity, Kevin Michael Braunscheidel

MUSC Theses and Dissertations

Volatile organic solvents like toluene induce euphoria and intoxication when inhaled at high concentrations. Inhalant misuse is linked to behavioral, cognitive, and anatomical deficits in humans leading to a reduced productivity and quality of life. Yet, preclinical studies on the effect of inhalants on executive control in animal models are limited. We address this gap in knowledge using rodent models in two ways: first, by examining the long-lasting effects of repeated toluene inhalation during adolescence on several measures of executive function in adulthood and second, by studying the effects of acute toluene inhalation on risk/reward decision making and related neurocircuitry. …

Examining Oxytocin As A Potential Pharmacotherapy For Methamphetamine Addiction, Brittney M. Cox

MUSC Theses and Dissertations

Human and animal studies suggest that females differ in their motivation to use methamphetamine (meth), and have increased propensity to relapse. However, addiction pharmacotherapies have primarily only been tested in males, which may not accurately predict treatment outcomes in females. Evidence suggests that oxytocin, an endogenous peptide well known for its role in social behaviors and childbirth, is a promising addiction pharmacotherapy. This dissertation first examines sex differences in the effect of oxytocin to decrease meth and sucrose seeking. Our data indicate that systemic oxytocin decreased responding for meth differentially in males and females on a progressive ratio schedule of …

The Effect Of Adolescent Alcohol On Dopaminergic And Gabaergic Neurotransmission In The Adult Prefrontal Cortex, Samuel W. Centanni

MUSC Theses and Dissertations

The prefrontal cortex (PFC) is thought to play an important role in cognitive processes that are negatively impacted by alcohol exposure. Compared to other brain regions, the neuronal connections of the PFC undergo a critical period of reorganization and refinement during adolescence that coincides with improvements in cognitive control and decision-making. Environmental insults that occur during this period may be particularly damaging to the PFC, resulting in aberrant neurodevelopment along with long-lasting effects on cognitive functioning that negatively impacts decision-making and behavioral control. Experimentation with alcohol typically begins during adolescence when it is often consumed in excessive binge-like episodes resulting …

Aiming Attention Using Selective Stimulation Of Locus Coeruleus And Its Medial Prefrontal Efferents, Zackary A. Cope

MUSC Theses and Dissertations

Appropriate modification of behavior in response to dynamic environmental conditions is essential for the adaptation and survival of most biological organisms. This adaptability allows for organisms to maximize the benefit of behavior related energy expenditure (utility) while minimizing cost. Modern theories of locus coeruleus (LC) function implicate a pivotal role for the noradrenergic (NA) nucleus in mediating switches between focused behavior during periods of high utility (exploit) versus disengagement of behavior and exploration of other, more rewarding opportunities. Two modes of activity in LC neurons have been well characterized. During periods of accurate and focused behavior, LC neurons exhibit suppressed …

The Role Of Bdnf Within The Medial Prefrontal Cortex On Relapse To Cocaine-Seeking Behavior, William J. Berglind

MUSC Theses and Dissertations

Glutamatergic pyramidal cells arising from the prefrontal cortex (PFC) are critical mediators of reinstatement to cocaine-seeking. A potent modulator of PFC activity is brain derived neurotrophic factor (BDNF), a molecule that has been implicated in the regulation of glutamatergic neurotransmission. In this study, the role of BDNF in the PFC was investigated in an animal model of cocaine addiction. First, a cocaine-induced decrease in BDNF mRNA within the PFC was documented following 22 h of abstinence, followed by an increase in BDNF protein expression within the PFC following 21 d of extinction training. Second, an intra-PFC infusion of BDNF attenuated …