Systems Neuroscience 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 …

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 …

A Multi-Modal Imaging Analysis Of Inter-Community Hub Nodes In Subjective Cognitive Decline Linking Longitudinal Hub Function Disruption To White Matter Integrity Kurtosis, Duncan Nowling

MUSC Theses and Dissertations

Subjective Cognitive Decline (SCD) has garnered much interest as a potential identifiable preclinical stage and indicator of risk for cognitive decline in Alzheimer’s Disease and related dementias (ADRD). Identification of individuals in this stage though is difficult, as they present with objectively normal cognitive evaluation scores, relying instead upon self-report of concern about decline in cognitive abilities. The use of non-invasive in-vivo imaging methods like BOLD functional imaging and diffusion tensor have allowed for complex mapping of both the functional and structural network features unique to this condition. This study furthers this network biomarker map of SCD by investigating the …

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. …

Characterizing The Temporal Dynamics In Functional Connectivity Measured With Fmri, Joshua Swearingen

MUSC Theses and Dissertations

There is a considerable and growing interest in the organization and development of neural function at the scale of the entire brain, particularly from activity observed in fluctuations in the blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This activity reliably organizes into sub-networks, whether obtained from subjects at rest or from those involved in various perceptual or cognitive tasks. While these networks have often been identified and studied, the precise dynamics involved in their interactions as well as the relationship between organization found in both resting and task-based activity are not well understood. Here I …