Neuroscience and Neurobiology Commons^™

Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade

Theses and Dissertations

Alzheimer’s disease is a progressive neurodegenerative disorder generally affecting people above the age of 65 years. Even though the pathophysiological hallmarks of AD were established more than a hundred years ago, there is yet to be a drug that can stop its characteristic neuronal damage. Of the five currently FDA-approved drugs, galantamine has a unique mechanism of action. Apart from being an AChE inhibitor, galantamine can effectively potentiate (positive allosteric modulator) the effect of agonists at nAChRs at concentrations lower than those required for its action as an AChE inhibitor. Perhaps the clinical benefits observed with galantamine are associated mainly …

Novel Calcium-Related Targets Of Insulin In Hippocampal Neurons, Shaniya Maimaiti, Hilaree N. Frazier, Katie L. Anderson, Adam O. Ghoweri, Lawrence D. Brewer, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Both insulin signaling disruption and Ca²⁺ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca²⁺-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca²⁺-dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in …

Optogenetic Interrogation Of Primary Visual Cortex And Its Impact On Neural Coding And Behavior, Ariana R. Andrei

Dissertations and Theses (Open Access)

Understanding the mechanism by which the brain transforms simple sensory inputs into rich perceptual experiences is one of the great mysteries of systems neuroscience. Undoubtedly this involves the activity of large populations of interconnected neurons, but while the responses of individual neurons to a variety of sensory stimuli have been well-characterized, how populations of such neurons organize their activity to create our sensory perceptions is almost entirely unknown. To investigate this complex circuitry requires the ability to causally manipulate the activity of neural populations and monitor the resultant effects. Here we focus on primary visual cortex (V1), which has been …

Neurometabolic And Electrophysiological Changes During Cortical Spreading Depolarization: Multimodal Approach Based On A Lactate-Glucose Dual Microbiosensor Arrays, Cátia F. Lourenço, Ana Ledo, Greg A. Gerhardt, João Laranjinha, Rui M. Barbosa

Center for Microelectrode Technology Faculty Publications

Spreading depolarization (SD) is a slow propagating wave of strong depolarization of neural cells, implicated in several neuropathological conditions. The breakdown of brain homeostasis promotes significant hemodynamic and metabolic alterations, which impacts on neuronal function. In this work we aimed to develop an innovative multimodal approach, encompassing metabolic, electric and hemodynamic measurements, tailored but not limited to study SD. This was based on a novel dual-biosensor based on microelectrode arrays designed to simultaneously monitor lactate and glucose fluctuations and ongoing neuronal activity with high spatial and temporal resolution. In vitroevaluation of dual lactate-glucose microbiosensor revealed an extended linear range, …

Transient Receptor Potential Cation Channel, Subfamilies V, Member 1 (Trpv1) And M, Member 1 (Trpm1) Contribute To Neural Signaling In Mouse Retina., Jennifer Noel

Electronic Theses and Dissertations

The retina processes light information through parallel pathways in order to extract and encode the visual scene. Light information is transmitted to the brain through approximately 30 ganglion cells (GCs), the retinal output neurons. Trp channels modulate the responses of retinal neurons within specific pathways. The study of the expression and function of the majority of Trp channels in the retina is largely in its infancy. My dissertation first investigated the expression and function of the transient receptor potential vanilloid-1 (TRPV1) receptor/channel in the retina. TRPV1, the first cloned and most highly studied Trp channel in the peripheral nervous system, …

Adult Neurogenesis In Avian Auditory Cortex, Caudomedial Nidopallium (Ncm): Lateralization And Effects Of Statins, Shuk C. Tsoi

Dissertations, Theses, and Capstone Projects

In the first part of this paper, we investigated the basic relationship between learning, memory and adult neurogenesis using zebra finches. We found that in the auditory cortex, the left hemisphere had more new neurons than the right hemisphere. This lateralization was correlated with song learning and memory. In the second part, we used juvenile zebra finches as a model organism to study the effects of Lipitor on learning, memory and neurogenesis. We found that Lipitor impaired song learning and memory storage. Lipitor treatments also changed the morphology of new neurons and size of old neurons, suggesting statins may affect …

Synaptic Homeostasis At The Drosophila Neuromuscular Junction: Molecular Mechanisms And Developmental Adaptation, Lindsay A. Gray

Dissertations, Masters Theses, Capstones, and Culminating Projects

No abstract available

Novel Pharmacological Target: Characterization Of A3b2 Nachrs Expressed In Xenopus Laevis Oocytes, Doris Jackson, Marcel Hall, J. Kolb, B. Todd Jr., D. Pugh, B. Vance, B. Klienstuber, R. Drecketts, S. N. Sudweeks

FHSS Mentored Research Conference

We have identified two subtypes of the novel a3b2 nicotinic acetylcholine receptor (nAChR) found within interneurons of the hippocampus. This novel receptor may be a valuable pharmacological target in drug development for disease such as Alzheimer’s disease (AD) which is largely characterized by degeneration of the hippocampus.

The Effect Of Silver Nanoparticles On Synaptic Responses In The Lateral Giant Escape Circuit Of The Crayfish, Samantha N. Adkins

Theses, Dissertations and Capstones

The lateral giant neuron in the crayfish is a neuron that controls the reflexive escape response; the context and experience-dependent tuning of this response is critical for survival. Serotonin modulates synaptic responses in this neuron, and social experiences (stress) changes the modulatory role of serotonin. I investigated the mechanisms of induced synaptic response changes and serotonergic modulatory changes after silver nanoparticle exposure to ask if 1) contaminant induced stress changes serotonergic modulation in a manner consistent with social stress and 2) shed light on potential neurotoxic effects of widely used, but poorly understood nanomaterials. Our data show that stress induced …

Cortisol Levels And Voltage Conditions Of College Students, Adriana Steffens

Walden Dissertations and Doctoral Studies

There is a limited research base on low voltage brain conditions, which are characterized by electrical activity being measured at below 20 microvolts. The purpose of this study was to examine the relationship between saliva cortisol levels and voltage using an EGG in a college student population. Illuminating this relationship is important to inform how low voltage conditions can affect daily memory and cognitive functioning of undergraduate college students that may be a result of stress. The college student population may be vulnerable to the low voltage condition because of stress from the transition between teenage and adult life and …

Effect Of Somatostatin On Voltage-Gated Calcium Influx In Isolated Neonatal Rat Carotid Body Type I Cells, Eric J. Dunn

Browse all Theses and Dissertations

Somatostatin (SST) is a neuropeptide hormone that regulates the release of secondary hormones. Evidence suggests SST plays a neuromodulatory role due to its distribution throughout the central nervous system. Interestingly, SST has been suggested to affect the carotid body, the small peripheral chemoreceptors that regulate breathing. It has been shown that the peripheral chemoreflex sensitivity to CO2 and hypoxia is reduced by SST in humans (Pedersen et al., 1999; Pandit et al., 2014). SST has also been found to inhibit whole cell Ca2+ currents recorded from adult rat carotid body type I cells (e Silva & Lewis, 1995), but the …

Biological Motion Processing In Typical Development And In The Autism Spectrum, Aaron Krakowski

Dissertations, Theses, and Capstone Projects

Biological motion (BM) analysis and interpretation is a fundamental process of human neurocognition that has been only minimally explored neurophysiologically. In addition to its importance in understanding the underlying roots and development of social cognition, BM processing is a prime candidate domain for exploring the underlying etiology of social cognitive disorders such as the autism spectrum.

In an initial experiment, typical adults observed BM point-light displays of a human actor (UM) as well as their spatially scrambled counterparts (SM), in both an unattended distractor task as well as an explicit attention task. Results showed a neurophysiological response manifested as three …

Effects Of Resting State On Perceptual Learning, Sarah Eagleman Ph.D.

Dissertations and Theses (Open Access)

Psychophysical experiments in humans have demonstrated that improvements in perceptual learning tasks occur following daytime rests. The neural correlates of how rest influences subsequent sensory processing during these tasks remain unclear. One possible neural mechanism that may underlie this behavioral improvement is reactivation. Previously evoked network activity reoccurs – reactivates - in the absence of further stimulation. Reactivation was initially discovered in the hippocampus but has now been found in several brain areas including cortex. This phenomenon has been implicated as a general mechanism by which neural networks learn and store sensory information. However, whether reactivation occurs in areas relevant …

Exploring Emotions Using Invasive Methods: Review Of 60 Years Of Human Intracranial Electrophysiology, Sean A. Guillory, Krzysztof A. Bujarski

Dartmouth Scholarship

Over the past 60 years, human intracranial electrophysiology (HIE) has been used to characterize seizures in patients with epilepsy. Secondary to the clinical objectives, electrodes implanted intracranially have been used to investigate mechanisms of human cognition. In addition to studies of memory and language, HIE methods have been used to investigate emotions. The aim of this review is to outline the contribution of HIE (electrocorticography, single-unit recording and electrical brain stimulation) to our understanding of the neural representations of emotions. We identified 64 papers dating back to the mid-1950s which used HIE techniques to study emotional states. Evidence from HIE …

The Neurodevelopment Of Basic Sensory Processing And Integration In Autism Spectrum Disorder, Alice Brown Brandwein

Dissertations, Theses, and Capstone Projects

This thesis presents three studies that together explore the neurophysiological basis for the sensory processing and integration abnormalities that have been observed in autism spectrum disorder (ASD) since the disorder was first described over half a century ago. In designing these studies we seek to fill a hole that currently exists in the research community‟s knowledge of the neurodevelopment of basic multisensory integration -- both in children with autism and as well as in those with typical development. The first study applied event related potentials (ERPs) and behavioral measures of multisensory integration to a large group of healthy participants ranging …

An In Vivo Assay For Simultaneous Monitoring Of Neuronal Activity And Behavioral Output In The Stomatogastric Nervous System Of Decapod Crustaceans, Wolfgang Stein, Florian Diehl

Faculty Publications – Biological Sciences

Central pattern generators (CPGs) generate rhythmic output patterns and drive vital behaviors such as breathing, swallowing, locomotion and chewing ^1-10. While most insights into the rhythm generating mechanisms of CPGs have been derived from isolated nervous system preparations, the relationship between neural activity and corresponding behavioral expression is often unclear. The stomatogastric system of decapod crustaceans is one of the best characterized neural system for motor pattern generation ^9-12 and many mechanisms of motor pattern generation and selection have been discovered in this system. Since most studies are limited to the isolated nervous system, little is known about the …

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

Short Duration Waveforms Recorded Extracellularly From Freely Moving Rats Are Representative Of Axonal Activity, Ashlee A. Robbins, Steven E. Fox, Gregory L. Holmes, Rod C. Scott, Jeremy M. Barry

Dartmouth Scholarship

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation …

Modulation Of Synaptic Transmission By Adenosine In Layer 2/3 Of The Rat Visual Cortex In Vitro, Nicholas M. Bannon

Master's Theses

No abstract provided.

Nmda Receptors In The Dorsal Vagal Complex Of Normal And Diabetic Mice, Eva C. Bach

Theses and Dissertations--Physiology

The dorsal vagal complex (DVC), containing the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMV), plays a pivotal role in autonomic regulation. Afferent fibers from peripheral organs and higher brain centers synapse in the NTS, which integrates these synaptic connections as well as information from systemically circulating hormones and metabolites. The integrated information is relayed to the dorsal motor nucleus of the vagus nerve (DMV), which in turn, projects motor fibers to elicit parasympathetic control of digestive and other viscera. Physiological functions mediated by the DVC are disrupted in diabetic patients and …

Structural Analysis Of The Drosophila Innexin Shakb: Role Of The N-Terminus In Rectifying Electrical Synapses, William Marks

Biology Theses

Gap junction channels mediate direct intercellular communication in all multicellular animals. They are comprised of the connexin family of proteins in vertebrates and the innexin family in prechordates. Connexins and innexins share many functional and structural similarities as orthologous proteins. Both types are capable of forming electrical synapses. Rectifying junctions are specialized electrical synapses found in neural systems that control escape responses. It has been shown that heterotypic gap junction channels mediate asymmetric properties of rectifying junctions. Shaking B N+16 and Shaking B lethal are variants of the ShakB locus in Drosophila and the organization of these innexins into heterotypic …

Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang

Legacy Theses & Dissertations (2009 - 2024)

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various …

“What” And “Where” In Auditory Sensory Processing: A High-Density Electrical Mapping Study Of Distinct Neural Processes Underlying Sound Object Recognition And Sound Localization, Victoria M. Leavitt, Sophie Molholm, Manuel Gomez-Ramirez, John J. Foxe

Publications and Research

Functionally distinct dorsal and ventral auditory pathways for sound localization (WHERE) and sound object recognition (WHAT) have been described in non-human primates. A handful of studies have explored differential processing within these streams in humans, with highly inconsistent findings. Stimuli employed have included simple tones, noise bursts, and speech sounds, with simulated left–right spatial manipulations, and in some cases participants were not required to actively discriminate the stimuli. Our contention is that these paradigms were not well suited to dissociating processing within the two streams. Our aim here was to determine how early in processing we …

Synaptic Reorganization Of Inhibitory Hilar Interneuron Circuitry After Traumatic Brain Injury In Mice, Robert F. Hunt, Stephen W. Scheff, Bret N. Smith

Physiology Faculty Publications

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found …

Minimal Information For Neural Electromagnetic Ontologies (Minemo): A Standards-Compliant Method For Analysis And Integration Of Event-Related Potentials (Erp) Data, Gwen Frishkoff, Jason Sydes, Kurt Mueller, Tim Curran, John F. Connolly, Kerry Kilborn, Dennis L. Molfese, Charles Perfetti, Allen D. Malony

Center for Brain, Biology, and Behavior: Faculty Publications

We present MINEMO (Minimal Information for Neural ElectroMagnetic Ontologies), a checklist for the description of event-related potentials (ERP) studies. MINEMO extends MINI (Minimal Information for Neuroscience Investigations)to the ERP domain. Checklist terms are explicated in NEMO, a formal ontology that is designed to support ERP data sharing and integration. MINEMO is also linked to an ERP database and web application (the NEMO portal). Users upload their data and enter MINEMO information through the portal. The database then stores these entries in RDF (Resource Description Framework), along with summary metrics, i.e., spatial and temporal metadata. Together these spatial, temporal, and functional …

A Functional Role For The Ventrolateral Prefrontal Cortex In Non-Spatial Auditory Cognition, Y. E. Cohen, B. E. Russ, S. J. Davis, A. E. Baker, A. L. Ackelson, R. Niteck

Dartmouth Scholarship

Spatial and non-spatial sensory information is hypothesized to be evaluated in parallel pathways. In this study, we tested the spatial and non-spatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the non-spatial pathway. Activity was tested while non-human primates reported changes in an auditory stimulus' spatial or non-spatial features. We found that vPFC neurons were reliably modulated during a non-spatial auditory task but were not modulated during a spatial auditory task. The degree of modulation during the non-spatial task correlated positively with the monkeys' behavioral performance. These results are consistent with the hypotheses that …