Neurosciences Commons^™

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

Submandibular Mechanical Stimulation Of Upper Airway Muscles To Treat Obstructive Sleep Apnea, Ferhat Erdogan

Dissertations

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to keep a patent airway during respiration in wakefulness and sleep. The activity of genioglossus, the primary tongue-protruding muscle playing an important role in this coordination, is known to be modulated by several reflex pathways mediated through the mechanoreceptors of the upper airways. The main objective is to investigate the effectiveness of activating these reflex pathways with mechanical stimulations, for the long-term goal of improving the upper airway patency during disordered breathing in sleep. The genioglossus response is examined during mandibular and sub-mandibular mechanical stimulations in healthy subjects during …

Cortical Statistical Correlation Tomography Of Eeg Resting State Networks, Chuang Li, Han Yuan, Guofa Shou, Yoon-Hee Cha, Sridhar Sunderam, Walter Besio, Lei Ding

Biomedical Engineering Faculty Publications

Resting state networks (RSNs) have been found in human brains during awake resting states. RSNs are composed of spatially distributed regions in which spontaneous activity fluctuations are temporally and dynamically correlated. A new computational framework for reconstructing RSNs with human EEG data has been developed in the present study. The proposed framework utilizes independent component analysis (ICA) on short-time Fourier transformed inverse source maps imaged from EEG data and statistical correlation analysis to generate cortical tomography of electrophysiological RSNs. The proposed framework was evaluated on three sets of resting-state EEG data obtained in the comparison of two conditions: (1) healthy …

Novel Tnf Receptor-1 Inhibitors Identified As Potential Therapeutic Candidates For Traumatic Brain Injury, Rachel K. Rowe, Jordan L. Harrison, Hongtao Zhang, Adam D. Bachstetter, David P. Hesson, Bruce F. O'Hara, Mark I. Greene, Jonathan Lifshitz

Sanders-Brown Center on Aging Faculty Publications

Background: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio-indicator of inflammation. We hypothesized the efficacy of novel …

Neural Responses To Naturalistic Clips Of Behaving Animals Under Two Different Task Contexts, Samuel A. Nastase, Yaroslav O. Halchenko, Andrew C. Connolly, M. Ida Gobbini, James V. Haxby

Dartmouth Scholarship

The human brain rapidly deploys semantic information during perception to facilitate our interaction with the world. These semantic representations are encoded in the activity of distributed populations of neurons (Haxby et al., 2001; McClelland and Rogers, 2003; Kriegeskorte et al., 2008b) and command widespread cortical real estate (Binder et al., 2009; Huth et al., 2012). The neural representation of a stimulus can be described as a location (i.e., response vector) in a high-dimensional neural representational space (Kriegeskorte and Kievit, 2013; Haxby et al., 2014). This resonates with behavioral and theoretical work describing mental representations of objects and actions as being …

Regional Microglia Are Transcriptionally Distinct But Similarly Exacerbate Neurodegeneration In A Culture Model Of Parkinson's Disease., Eric Wildon Kostuk, Jingli Cai, Lorraine Iacovitti

Department of Neuroscience Faculty Papers

BACKGROUND: Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN are still mostly unknown. Here, we demonstrate the importance of balance between astrocytes and microglia in the susceptibility of SN DA neurons to the PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP

METHODS: Previously established methods were used to isolate astrocytes and microglia from the cortex (CTX), SN, and VTA, as well as embryonic midbrain DA neurons from the …

Organic Cation Transporter 3: A Cellular Mechanism Underlying Rapid, Non-Genomic Glucocorticoid Regulation Of Monoaminergic Neurotransmission, Physiology, And Behavior, Paul J. Gasser, Christopher A. Lowry

Biomedical Sciences Faculty Research and Publications

Corticosteroid hormones act at intracellular glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) to alter gene expression, leading to diverse physiological and behavioral responses. In addition to these classical genomic effects, corticosteroid hormones also exert rapid actions on physiology and behavior through a variety of non-genomic mechanisms, some of which involve GR or MR, and others of which are independent of these receptors. One such GR-independent mechanism involves corticosteroid-induced inhibition of monoamine transport mediated by “uptake₂” transporters, including organic cation transporter 3 (OCT3), a low-affinity, high-capacity transporter for norepinephrine, epinephrine, dopamine, serotonin and histamine. Corticosterone directly and acutely inhibits …

Cdk5 Inhibition Resolves Pka/Camp-Independent Activation Of Creb1 Signaling In Glioma Stem Cells, Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Hithardhi Duggireddy, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel J. Brat

Neurology Faculty Publications

Cancer stem cells promote neoplastic growth, in part by deregulating asymmetric cell division and enhancing self-renewal. To uncover mechanisms and potential therapeutic targets in glioma stem cell (GSC) self-renewal, we performed a genetic suppressor screen for kinases to reverse the tumor phenotype of our Drosophila brain tumor model and identified dCdk5 as a critical regulator. CDK5, the human ortholog of dCdk5 (79% identity), is aberrantly activated in GBMs and tightly aligned with both chromosome 7 gains and stem cell markers affecting tumor-propagation. Our investigation revealed that pharmaceutical inhibition of CDK5 prevents GSC self-renewal in vitro and in xenografted tumors, at …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

Treating Adhd With Suggestion: Neurofeedback And Placebo Therapeutics, Robert T. Thibault, Samuel Vassière, Jay A. Olson, Amir Raz

Psychology Faculty Articles and Research

Objective: We propose that clinicians can use suggestion to help treat conditions such as ADHD. Methods: We use EEG neurofeedback as a case study, alongside evidence from a recent pilot experiment utilizing a sham MRI scanner to highlight the therapeutic potential of suggestion-based treatments. Results: The medical literature demonstrates that many practitioners already prescribe treatments that hardly outperform placebo comparators. Moreover, the sham MRI experiment showed that, even with full disclosure of the procedure, suggestion alone can reduce the symptomatology of ADHD. Conclusion: Non-deceptive suggestion-based treatments, especially those drawing on accessories from neuroscience, may offer a safe complement and potential …

Neural Mechanisms Of The Rejection-Aggression Link, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection–aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex’s (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain’s mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain’s reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was associated with greater levels of …

Pituitary Adenylate Cyclase-Activating Polypeptide (Pacap) Signaling In The Prefrontal Cortex Modulates Cued Fear Learning, But Not Spatial Working Memory, In Female Rats, Adam J. Kirry, Matthew R. Herbst, Sarah E. Poirier, Michelle M. Maskeri, Amy C. Rothwell, Robert C. Twining, Marieke R. Gilmartin

Biomedical Sciences Faculty Research and Publications

A genetic polymorphism within the gene encoding the pituitary adenylate cyclase- activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues. Moreover, a neurobiological substrate that may account for the observed link between PAC1R and PTSD in women, but not men, has yet to …

Synaptic Nanomodules Underlie The Organization And Plasticity Of Spine Synapses., Martin Hruska, Nathan T. Henderson, Sylvain J. Le Marchand, Haani Jafri, Matthew B. Dalva

Department of Neuroscience Faculty Papers

Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size. Live-cell time-lapse super-resolution imaging reveals that NMDA receptor-dependent increases in spine size are accompanied both by enhanced mobility of …

Behavior Coding Strategies: Population Coupling And The Functional Role Of Excitatory/Inhibitory Balance In Primary Motor Cortex, Patrick Aaron Kells

Graduate Theses and Dissertations

The complexities of an organism’s experience of- and interaction with the world are emergent phenomena produced by large populations of neurons within the cerebral cortex and other brain regions. The network dynamics of these populations have been shown to be sometimes synchronous, with many neurons firing together, and sometimes asynchronous, with neurons firing more independently, leading to a decades-old debate within the neuroscience community. This discrepancy comes from viewing the system at two different scales; at the single cell level, the spiking activity of two neurons within cortex tend to be rather independent, but when the average activity of a …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Common Ribs Of Inhibitory Synaptic Dysfunction In The Umbrella Of Neurodevelopmental Disorders, Rachel Ali Rodriguez, Christina Joya, Rochelle M. Hines

Psychology Faculty Research

The term neurodevelopmental disorder (NDD) is an umbrella term used to group together a heterogeneous class of disorders characterized by disruption in cognition, emotion, and behavior, early in the developmental timescale. These disorders are heterogeneous, yet they share common behavioral symptomatology as well as overlapping genetic contributors, including proteins involved in the formation, specialization, and function of synaptic connections. Advances may arise from bridging the current knowledge on synapse related factors indicated from both human studies in NDD populations, and in animal models. Mounting evidence has shown a link to inhibitory synapse formation, specialization, and function among Autism, Angelman, Rett …

Thalamocortical Processing Of Temporal Cues In Sounds, Kasey Smith

Honors Scholar Theses

The ability of the brain to extract meaningful information from complex sounds is what allows mammals to understand species-specific communication as well as important environmental cues such as the sound of water or of potential predators or prey. The auditory cortex of humans and other mammals contains multiple cortical regions that unique sensitivities to both spectral and temporal sound cues. This discourse will explore three main factors proposed to determine these distinct processing capabilities in regard to temporal sound cues; the distribution of glutamate transporters in the thalamus, the architecture of afferent pathways between the thalamus and auditory cortex, and …

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.

Freedom With Responsibility: A Consensus Strategy For Preventing Injury, Death, And Disability From Firearm Violence, Ronald M. Stewart Md, Facs, Deborah A. Kuhls Md, Facs, Michael F. Rotondo Md, Facs, Eileen M. Bulger Md, Facs

School of Medicine Faculty Publications

We are surgeons who have committed our personal and professional lives to reducing needless suffering from injury. As leaders in the American College of Surgeons Committee on Trauma (ACS COT), we have put our hearts and souls into reducing firearm violence, yet we continue to experience the senseless tragedy of mass shooting events and the daily impact of violence on our patients and our communities. Two of us (DK, RMS) personally cared for innocent victims in 2 of the largest mass shootings in modern American history: the Las Vegas, NV and Sutherland Springs, TX tragedies, which, within a little more …

Modified Origins Of Cortical Projections To The Superior Colliculus In The Deaf: Dispersion Of Auditory Efferents., Blake E Butler, Julia K Sunstrum, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (