Neuroscience and Neurobiology Commons^™

Polarity And Competition In The Development Of The Calyx Of Held Terminal In The Medial Nucleus Of The Trapezoid Body In The Mouse, Paul Steven Holcomb

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the auditory brainstem, the connection between globular bushy cells of the anteroventral cochlear nucleus and principal cells (PCs) of the medial nucleus of the trapezoid body (MNTB) is created by one of the largest nerve terminals in the central nervous system, the calyx of Held (CH). The characteristics of the CH:MNTB connection—a short developmental period (48-72 hours), accessibility for recording from pre- and postsynaptic components, and clear monoinnervated end point—make this system an ideal model system for studying nervous system development. Model systems undergo stereotyped stages of development, including exuberant overinnervation, competition between terminals, and a refinement of innervation …

The Integration Of Extrinsic And Intrinsic Neuromodulators In The Olfactory System, Kristyn M. Lizbinski

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics by adjusting the biophysical and synaptic properties of neurons. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e. neurons that participate in network coding) or an extrinsic origin (i.e. neurons from independent networks). Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. Furthermore, nervous systems are continually subject to a dynamic cocktail of both intrinsic and extrinsic modulators. However, …

Preserved Consciousness In The Absence Of A Cerebral Cortex, The Legal And Ethical Implications Of Redefining Consciousness And Its Neural Correlates: A Case For A Subcortical System Generating Affective Consciousness, Shadia Kawkabani

Williams Honors College, Honors Research Projects

Historically, the scientific and medical communities have taken a corticocentric view on consciousness, emphasizing the need for a cortex in producing the conscious experience. The preserved consciousness observed in hydranencephalic children and decorticated rats suggests that some form of consciousness may be produced by a subcortical network. The brainstem, a phylogenetically ancient and conserved brain structure, could serve as the major integrative machinery to produce this form of consciousness, which is called affective consciousness—the evolutionary antecedent to the reflective consciousness that allows humans to reflect on their experiences. The functional convergence of the brainstem with the amygdala, motor system, and …

Vascular Cognitive Impairment And Dementia: The Importance Of Mixed Pathologies From Mouse Models To Humans, Alex Marian Helman

Theses and Dissertations--Molecular and Cellular Biochemistry

Age-related neurologic disease is a significant and growing burden on our society. Although the largest share of research effort has typically been devoted to the common neurodegenerative illnesses (such as Alzheimer’s disease, or AD), the reality is that nearly all cases of neurodegenerative disease possess elements of mixed pathology. Vascular contributions to cognitive impairment and dementia (VCID) is a complex form of dementia, combining aspects of vascular disease and other forms of dementia, such as Alzheimer’s disease. This pathology is heterogeneous and can include cerebral amyloid angiopathy (CAA), hemorrhages, white matter infarcts, and changes to the neurovascular unit. Given the …

The Many Faces Of Fear And Vigilance, Guy Beauchamp

Animal Sentience

In the target article, I examined the relationship between vigilance and fear in prey animals. The joint occurrence of vigilance and other physiological responses to fear, such as increased heart rate and stress hormone release, would bolster the idea that vigilance can be a useful marker of fear. Nevertheless, a common theme in much of the empirical research is an uncoupling of vigilance and physiological correlates of fear. The commentators suggest several ways to refine the concepts of vigilance, fear, and risk. I discuss these refinements, which in the end will prove useful to assess further the relationship between vigilance …

A Comparative Study Of Sleep, Diurnal Patterns, And Eye Closure Between The House Mouse (Mus Musculus) And African Spiny Mouse (Acomys Cahirinus), Chanung Wang

Theses and Dissertations--Biology

To understand the function and origins of sleep, sleep needs to be studied across many different species. Although it is well conserved throughout mammals, 95% of papers are restricted to just three species, Homo sapiens, Mus musculus, and Rattus norvegicus. We aimed to characterize sleep and wake in a Murid rodent Acomys cahirinus in greater detail alongside the well-studied laboratory house mouse (Mus musculus) and wild M. musculus using a well validated, non-invasive, piezoelectric system for sleep and activity monitoring. We confirmed A. cahirinus, M. musculus, and wild M. musculus to be primarily …

A Behavioral Mechanistic Investigation Of The Role Of 5-Ht1a Receptors In The Mediation Of Rat Maternal Behavior, Xiaonan Li, Xiaojing Ding, Ruiyong Wu, Leilei Chen, Jun Gao, Gang Hu, Ming Li

Department of Psychology: Faculty Publications

Previous work suggests that 5-HT_1A receptors play a special role in rodent maternal aggression, but not in other aspects of maternal care (e.g. pup retrieval and nest building). The present study re-assessed the basic effects of 5-HT_1A activation or blockade on various maternal responses in postpartum female rats. We also examined the possible behavioral mechanisms underlying the maternal effects of 5-HT_1A. Sprague–Dawley mother rats were injected with a 5-HT_1A agonist 8-OH-DPAT (0.1, 0.5 or 1.0 mg/kg, sc), a 5-HT_1A antagonist WAY-101405 (0.1, 0.5 or 1.0 mg/kg, sc) or 0.9% saline solution on postpartum days …

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT_2A-dependent upregulation of histone deacetylase 2 …

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 …

Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin

Theses and Dissertations

The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations, …

On Crabs And Statistics, Jonathan Birch

Animal Sentience

I respond to commentaries by Elwood and Seth & Dienes and to a recent critique by Diggles, discussing the link between avoidance learning and sentience, the relevance of the clash between frequentist and Bayesian statistics, the risks to decapod welfare in aquaculture, and the broader concerns one may have about a “precautionary” approach to protecting invertebrates.

Spatial Learning And Memory In Brain-Injured And Non-Injured Mice: Investigating The Roles Of Diacylglycerol Lipase-Α And -Β., Lesley D. Schurman

Theses and Dissertations

A growing body of evidence implicates the importance of the endogenous cannabinoid 2-arachidonyl glycerol (2-AG) in memory regulation. The biosynthesis of 2-AG occurs primarily through the diacylglycerol lipases (DAGL-α and -β), with 2-AG serving as a bioactive lipid to both activate cannabinoid receptors and as a rate limiting precursor for the production of arachidonic acid and subsequent pro-inflammatory mediators. Gene deletion of DAGL-α shows decrements in synaptic plasticity and hippocampal neurogenesis suggesting this biosynthetic enzyme may be important for processes of normal spatial memory. Additionally, 2-AG is elevated in response to pathogenic events such as traumatic brain injury (TBI), suggesting …

Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang

Theses and Dissertations

Cannabis (Marijuana) has multiple effects on the human body, such as analgesia, euphoria and memory impairment. Delta-9 tetrahydrocannabinol (D9-THC), the active ingredient in cannabis, binds to cannabinoid receptors, seven-transmembrane G protein-coupled receptors (GPCRs) that mediate a variety of physiological functions. GPCRs were believed to function only in homomeric forms, however, recent findings show that different GPCRs can also form heteromeric complexes that may expand their signaling properties. In this study, we focused on Cannabinoid CB1 receptor (CB1R) heteromers with the mu-opioid receptor (MOR) and the Dopamine type 2 receptor (D2R), respectively. We utilized a variety of techniques, such as the …

Mechanisms Regulating Axon Initial Segment Stability, Savannah D. Benusa

Theses and Dissertations

Axon initial segment (AIS) disruption has been described in a number of pathological environments where neuroinflammation is a contributing factor; however, whether this disruption is reversible in unknown. To address the principle of AIS structural recovery, we employed an acute neuroinflammatory model. Acute neuroinflammation induced disruption of AIS structural and functional domains and, importantly, upon resolution of neuroinflammatory conditions, was reversed.

Consistent with other studies, we observed a close interaction of microglia with AISs, and utilized this acute neuroinflammatory model to investigate the relationship between reactive microglia and AIS integrity. Gene expression analysis of microglial transcription profiles identified reactive oxygen …

Complexities Of Chronic Opioid Exposure, Maciej Gonek

Theses and Dissertations

Studies on repeated exposure to opioids have been carried out for decades yet the mechanisms for certain phenomena such as tolerance are still not fully understood. Furthermore, different medications, such as frequently prescribed benzodiazepines, or different disease states, such as HIV, have their own effects and interactions with chronic opioid exposure that are not fully understood. The overall objective of this dissertation was to investigate the complexities of chronic opioid exposure and how different disease states and medications may modulate the effects of chronic opioids. Our findings demonstrate that the administration of diazepam, at doses that are not antinociceptive or …

Functional Investigation Of A Brainstem Excitatory Connection Relevant To Sensorimotor Gating, Luis Enrique Martinetti

Open Access Theses & Dissertations

To focus attention, our brain has to "gate" or block irrelevant sensory information that could lead to brain overload. This is done by way of a neuronal pre-attentive mechanism termed sensorimotor gating (SG). Therefore, deficits in the SG mechanism prevent patients from focusing attention. SG deficits have been observed in patients suffering from various neurological disorders, and it is a hallmark of schizophrenia. Previous work has identified key brain areas, such as the pedunculopontine tegmental nucleus (PPTg), that send inputs to the brainstem to regulate SG. However, there is still a knowledge gap concerning what cell types are involved and …

Potential Candidates For Treating Deficits Associated With Developmental Ethanol Exposure In A Rodent Model: Solidago Nemoralis & Dimethoxybenzylidene-Anabasine, Logan James Fields

Theses and Dissertations--Psychology

Prenatal alcohol exposure (Fetal Alcohol Syndrome [FAS] and Fetal Alcohol Spectrum Disorders [FASD’s]) represents the leading preventable cause of intellectual disabilities in the western world, with FASDs estimated to affect approximately 2-5% of live births in the United States at an approximate annual cost of $3.6 billion (CDC, 2015; May et al., 2009). Ethanol (ETOH) exposure during development can lead to a variety of long-term behavioral impairments including problems with executive functioning, motor coordination, spatial learning, attention, and hyperactivity (Jones, 2011; Mattson & Riley, 1998). Much research has been conducted to develop pharmacological and/or environmental interventions to reduce these deficits, …

Finding Influential Nodes For Integration In Brain Networks Using Optimal Percolation Theory, Gino Del Ferraro, Andrea Moreno, Byungjoon Min, Flaviano Morone, Úrsula Pérez-Ramírez, Laura Pérez-Cervera, Lucas C. Parra, Andrei Holodny, Santiago Canals, Hernán A. Makse

Publications and Research

Global integration of information in the brain results from complex interactions of segregated brain networks. Identifying the most influential neuronal populations that efficiently bind these networks is a fundamental problem of systems neuroscience. Here, we apply optimal percolation theory and pharmacogenetic interventions in vivo to predict and subsequently target nodes that are essential for global integration of a memory network in rodents. The theory predicts that integration in the memory network is mediated by a set of low-degree nodes located in the nucleus accumbens. This result is confirmed with pharmacogenetic inactivation of the nucleus accumbens, which eliminates the formation of …