Systems Neuroscience Commons^™

Robust And Generalizable Representations In The Hippocampus, Hung-Tu Chen

Dartmouth College Ph.D Dissertations

An intelligent system must balance generalizing across similar experiences with maintaining the distinctiveness of each experience. This thesis explores how the hippocampus manages this balance through its neural representations to support adaptive behavior. In Chapter 1, I provide an overview of key hippocampal phenomena that contribute to this process, including remapping, splitter signal, and replay. In Chapter 2, I challenge the concept of random remapping by showing that it is possible to predict, better than chance, how a given experience will be encoded in the hippocampus across different subjects. This suggests that encoding of related experiences, which was previously thought …

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 …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Local Geometry Of Elementary Visual Computations, Peter Neri

MODVIS Workshop

Visual operators (e.g. edge detectors) are classically modelled using small circuits involving canonical computations, such as template-matching and gain control. Circuit models explain many aspects of the empirical descriptors that are used to characterize local visual operators, from sensitivity to classification images. Notwithstanding their utility, these models fail to provide a unified framework encompassing the variety of effects observed experimentally, such as the impact of contrast, SNR, and attention on the above descriptors. My goal is to start with a simple, plausible geometrical representation of the perceptual operation carried out by the observer, and to show that this representation is …

Characterization Of Perceptual Spaces From Triadic Similarity Judgments, Jonathan Victor

MODVIS Workshop

Perceptual spaces are mental workspaces that organize a sensory or cognitive domain into a format that supports functions such as comparison, grouping, learning, and generalization. Determining the geometry of a perceptual space – i.e., the properties of the perceptual distances within the space -- is thus crucial not only to understand these intermediate levels of processing at an algorithmic level, but also as a starting point for comparison with neural measures of similarity. While perceptual spaces are often taken to be Euclidean or nearly so (the classic example is trichromatic color space), this assumption, when tested, is often violated. Moreover, …

Individual Differences In Age And Testosterone Are Uniquely Associated With Neural Oscillatory Activity Serving Verbal Working Memory In Children And Adolescents, Abraham D. Killanin

Theses & Dissertations

During the sensitive period of adolescence, the human brain undergoes dynamic changes in structure and function resulting in vast executive function gains. Verbal working memory (VWM) is one executive function that serves as a foundation to language acquisition, reading, and learning. Many have examined the development of VWM in youth, but few have probed age-related changes in the underlying neural oscillatory dynamics, and none have examined testosterone-related changes. We recorded magnetoencephalography during a modified Sternberg VWM task in 82 youth participants aged 6 – 14 years old and collected salivary testosterone samples. Significant oscillatory responses were identified and imaged using …

The Effect Of Repetitive Transcranial Magnetic Stimulation On Brain And Cognitive Variables In Patients With Amnestic Mild Cognitive Impairment, Connor J. Phipps

Theses & Dissertations

Healthy and pathological aging processes can impact human memory. Current interventions for clinical memory impairment offer little opportunity for restoration of memory ability. Fortunately, a novel therapy in the form of repetitive transcranial magnetic stimulation (rTMS) has exhibited promise in this regard. In healthy adults, rTMS of the angular gyrus (AG) has been reported to improve memory. The current study sought to determine the generalizability of these findings to individuals with clinical memory impairment by administering a clinical trial replicating an rTMS protocol reported to improve hippocampal-dependent memory in healthy individuals to individuals with amnestic mild cognitive impairment (aMCI). Individuals …

Mapping The Neural Circuits That Underlie Metabolic Vs. Emotional Regulation Of Food-Seeking Behavior, Xu Zhang

Dissertations and Theses (Open Access)

Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations and Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

Sequence Learning In A 6-Ohda Mouse Model Of Parkinson’S Disease, Ani Gribbin

Neuroscience Honors Projects

Parkinson’s disease (PD), a neurodegenerative disorder originating in the dopaminergic cells of the basal ganglia, is characterized by severe motor impairments such as tremors, bradykinesia, and postural instability. However, non-motor symptoms impacting sensory systems and cognition are consistently pointed to as more greatly affecting quality of life for PD patients. Cognitive impairments in PD can include changes in reward processing, depression, apathy, and increases in risk-taking behavior. Additionally, learning and memory deficits are seen in PD, specifically in motor sequence learning. Often, the neural correlates of sequence learning impairments are traced to the substantia nigra. However, there is some evidence …

Dissecting The Tissue-Specific Contributions To Seizures, Cardiorespiratory Dysfunction, And Sudden Death In The Kv1.1 Mouse Model Of Epilepsy Using Conditional Knockout Approaches, Kelsey Paulhus

Biological Sciences Theses and Dissertations

Sudden unexpected death in epilepsy (SUDEP), the primary cause of mortality in epilepsy, remains poorly understood. Studies suggest seizures may trigger dangerous signals affecting the heart and lungs leading to collapse and death. The Kv1.1 deficiency mouse model mirrors clinical SUDEP cases, showing spontaneous seizures, cardiorespiratory issues, and premature death. However, this model lacks regional specificity in Kv1.1 deletion, hindering insights into SUDEP’s mechanisms and anatomical substrates.

This dissertation employs three distinct conditional knockout (cKO) techniques to investigate the individual roles for the forebrain, brainstem, and heart in SUDEP related phenotypes. The findings reveal that the forebrain alone can trigger …

Low-Dimensional Criticality Embedded In High-Dimensional Awake Brain Dynamics, Antonio J. Fontenele, J. Samuel Sooter, V. Kindler Norman, Shree Hari Gautam, Woodrow L. Shew

Physics Faculty Publications and Presentations

Whether cortical neurons operate in a strongly or weakly correlated dynamical regime determines fundamental information processing capabilities and has fueled decades of debate. We offer a resolution of this debate; we show that two important dynamical regimes, typically considered incompatible, can coexist in the same local cortical circuit by separating them into two different subspaces. In awake mouse motor cortex, we find a low-dimensional subspace with large fluctuations consistent with criticality—a dynamical regime with moderate correlations and multi-scale information capacity and transmission. Orthogonal to this critical subspace, we find a high-dimensional subspace containing a desynchronized dynamical regime, which may optimize …

Targeting Cholinergic Signaling In Glioblastoma, Sumyuktha Vijay Anand

Dartmouth College Ph.D Dissertations

Primitive stem cell-like populations that are prone to malignant transformation reside in the brain throughout adulthood. My lab’s reports and many others have characterized subsets of glioma cells reminiscent of adult stem-like cells implicating them rational candidates for cell-targeted therapies. Emerging evidence suggests that the neurotransmitter microenvironment influences these stem-like cells during glioma progression providing an inroad to study neuromodulators in glioma. Some glioma stemlike cells share characteristics with adult tissue oligodendrocyte progenitor cells. Primitive cells of the oligodendroglial lineage express muscarinic acetylcholine receptors (mAChRs), and their “stemness” is maintained by the acetylcholine (ACh) neurotransmitter. Here, I conduct transcriptomic, electrophysiological, …

A Causal Inference Approach For Spike Train Interactions, Zach Saccomano

Dissertations, Theses, and Capstone Projects

Since the 1960s, neuroscientists have worked on the problem of estimating synaptic properties, such as connectivity and strength, from simultaneously recorded spike trains. Recent years have seen renewed interest in the problem coinciding with rapid advances in experimental technologies, including an approximate exponential increase in the number of neurons that can be recorded in parallel and perturbation techniques such as optogenetics that can be used to calibrate and validate causal hypotheses about functional connectivity. This thesis presents a mathematical examination of synaptic inference from two perspectives: (1) using in vivo data and biophysical models, we ask in what cases the …

Synaptic Zinc Transporters Support Normal Synapse Structure And Function In Mouse Auditory Cortex, Abbey Manning

Graduate Theses, Dissertations, and Problem Reports (ETD)

Many regions of the brain are highly enriched with free zinc inside glutamatergic vesicles at presynaptic terminals. At these synapses, zinc transporter 3 (ZnT3) moves zinc into vesicles where it is co-released with glutamate. Alterations in ZnT3 are implicated in multiple neurodevelopmental disorders, and ZnT3 knock-out (KO) mice – which lack synaptic zinc – show behavioral deficits associated with autism spectrum disorder and schizophrenia. Shank3 is a synaptic scaffolding protein that assists in tethering and organizing structural proteins and glutamatergic receptors in the postsynaptic density of excitatory synapses. The localization of Shank3 at excitatory synapses and the formation of stable …

Sources And Termination Patterns Of Cholinergic Input To The Ventral Nucleus Of The Lateral Lemniscus, Emily Echols

Williams Honors College, Honors Research Projects

Neurons transmit signals through an electrochemical reaction: synapses on dendrites and the cell body receive neurotransmitters, and their effect on the cell determines the signal the cell will transmit. From dendrites to axon and then to another cell at a synaptic cleft, signals can propagate, enhance each other, or inhibit other transmissions until the message is received by the target area. Understanding the science behind neural signaling and structural function begins at the level of the synapse. The neurotransmitter acetylcholine (ACh) plays a substantial role in modulating neural activity in the auditory system, but for many brainstem nuclei the source …

Evaluating The Potential Of Using Eeg To Monitor Cognitive Workload In Simulated Suborbital Flight, Erik Seedhouse

Journal of Aviation/Aerospace Education & Research

Mental workload can be assessed using electrophysiological measures of brain activity, such as electroencephalography (EEG). EEG signals reveal cortical electrical activity. This cortical activity was recorded using specialized headsets. The focus of this research was to study cognitive performance (CP) in four pilots during simulated suborbital flights under nominal day and night profiles and under contingency day and night profiles. A 14-channel EMOTIV EEG headset measured the participants' brain activity while they flew simulated flights in a Suborbital Spaceflight Simulator (SSFS). Several sessions of EEG data were recorded from each subject, and feature extraction was applied. Data revealed that real-time …