Neuroscience and Neurobiology Commons^™

Locus Coeruleus And Hippocampal Tyrosine Hydroxylase Levels In A Pressure-Overload Model Of Heart Disease, Luke A. Johnson

Undergraduate Honors Theses

Studies have indicated that approximately 30% of people with heart disease experience major depressive disorder (MDD). Despite strong clinical evidence of a link between the two diseases, the neurobiological processes involved in the relationship are poorly understood. A growing number of studies are revealing similar neuroanatomical and neurochemical abnormalities resulting from both depression and heart disease. The locus coeruleus (LC) is a group of neurons in the pons that synthesize and release norepinephrine, and that is known to play a significant role in depression pathobiology. For example, there is evidence that tyrosine hydroxylase (TH) is elevated in the LC in …

Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung

Physiology and Pharmacology Publications

Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but …

Functional Roles Of The Insulin-Regulated Glucose Transporter-4 In The Hippocampus, Jiah Pearson-Leary

Legacy Theses & Dissertations (2009 - 2024)

Although a great deal of research has elucidated both localization and function of many glucose transporters (GluTs) throughout the brain, the function of brain insulin-responsive glucose transporter-4 (GluT4) remains unclear (McEwen & Reagan, 2004). Because type 2 diabetes mellitus (T2DM; insulin resistance, i.e., impaired insulin signaling) is a risk factor for Alzheimer's disease (AD), and because the signaling mechanisms insulin uses to mediate hippocampal processes and memory are unclear, a major purpose of this dissertation was to determine whether hippocampal GluT4, which is responsible for insulin's glucoregulatory and canonical effects in the periphery, is necessary for insulin's effects in the …

Delayed Amyloid Plaque Deposition And Behavioral Deficits In Outcrossed Aβpp/Ps1 Mice, Brian A. Couch, Meghan E. Kerrisk, Adam C. Kaufman, Haakon B. Nygaard, Stephen M. Strittmatter, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4–9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment …

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Stress- And Sex-Related Differences In The Activation Of Neuronal Subtypes In The Basolateral Amygdala Of The Rat, Alejandra E. Lopez, Christina C. Ruiz, Juan M. Bolanos, Jameel N. Hamdan, Kristin Gosselink

COURI Symposium Abstracts, Summer 2012

Previous studies suggest that stress alters the activational profiles among phenotypically-distinct subpopulations of neurons within the basolateral amygdala (BLA) of the rat. Given the connectivity of this region of the brain to the hippocampus, and the implications of the role of the BLA in modulating long-term potentiation associated with memory and learning, inferences of stress having a negative impact on cognition and memory can be drawn. Observations regarding stress response disparities between males and females in our model prompted the investigation of the role gender plays in cognition under conditions of stress, as well as the responses to stress itself. …

The Putative Cannabinoid Receptor Gpr55 Modulates Synaptic Plasticity In The Hippocampus, Corinne Marie Badgley

Theses and Dissertations

Endocannabinoids (eCBs) are small molecules that are capable of modulating synaptic plasticity of both excitatory and inhibitory synapses in the brain. While eCBs bind to transient receptor potential vanilloid 1 (TRPV1) and cannabinoid receptor 1 (CB1) in the central nervous system, we recently identified a form of non-CB1, non-TRPV1 mediated long term depression activated by the eCB anandamide at CA1 hippocampal stratum radiatum interneurons. GPR55, an orphan G-protein receptor, has been identified in the hippocampus and is capable of activation by eCBs, making it a good candidate for mediating this non-CB1, non-TRPV1 form of synaptic plasticity. Here we performed whole-cell …

Detection Of Sk2 Channels On Hippocampal Neurons, Jamie L. Maciaszek

Master's Theses

Calcium-activated small conductance potassium channels (SK) are crucial for synaptic plasticity, sleep, and learning and memory (Hammond, Bond et al. 2006; Cueni, Canepari et al. 2008; Lin, Lujan et al. 2008). Despite the recent progress on SK channel physiology, the precise spatial organization of SK channels in neurons has remained unknown. Such knowledge is critical as the subcellular distribution of SK channels is an important determinant of neuronal excitability. Currently, there are no techniques to image ion channel distribution quantitatively at the nanometer scale in living cells. Here, it is demonstrated that integration of natural toxins with single molecule atomic …

Vestibular And Attractor Network Basis Of The Head Direction Cell Signal In Subcortical Circuits, Benjamin J. Clark, Jeffrey S. Taube

Dartmouth Scholarship

Accurate navigation depends on a network of neural systems that encode the moment-to-moment changes in an animal's directional orientation and location in space. Within this navigation system are head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction (Sharp et al., 2001a; Taube, 2007). HD cells are widely thought to underlie an animal's sense of spatial orientation, and research over the last 25+ years has revealed that this robust spatial signal is widely distributed across subcortical and cortical limbic areas. The purpose of the present review is to summarize some of …

A Parametric Investigation Of Pattern Separation Processes In The Medial Temporal Lobe, Sarah E. Motley

Theses and Dissertations

The hippocampus is thought to be involved in memory formation and consolidation, with computational models proposing the process of pattern separation as a means for encoding overlapping memories. Previous research has used semantically related targets and lures to investigate hippocampal responses to mnemonic interference. Here, we attempted to define the response function of the hippocampus and its inputs during pattern separation by parametrically varying target-lure similarity in a continuous recognition task. We also investigated the effect of task demands (intentional versus incidental encoding) on pattern separation processes. We collected functional magnetic resonance imaging (fMRI) data while participants were shown a …

Spatial Working Memory And Adult Hippocampal Neurogenesis In Male Rats With Hight Fat Diet-Induced Obesity, Andrew Karl Recknagel

Legacy Theses & Dissertations (2009 - 2024)

Granule cells are continually produced in the dentate gyrus of the hippocampus throughout life. These new neurons integrate into the local circuitry and contribute to hippocampal function. Insulin directly affects hippocampal function and may also influence the process of adult neurogenesis. Some of the cognitive deficits that occur in Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) may be caused by hyperinsulinemia and systemic insulin resistance. Sedentary lifestyles combined with over-consumption of energy rich foods are responsible for the rising incidence of metabolic syndrome and chronic obesity, both of which represent major risk factors for T2DM and AD. Therefore, …

Septotemporal Variation In Theta Rhythm Dynamics: Effects Of Speed And Habituation, James Hinman

Master's Theses

Theta (6-12 Hz) field potentials and the synchronization (coherence) of these potentials present neural network indices of hippocampal physiology. Theta signals within the hippocampal formation may reflect alterations in sensorimotor integration, the flow of sensory input and/or distinct cognitive operations. While the power and coherence of theta signals vary across lamina within the septal hippocampus, limited information is available about variation in these indices across the septotemporal (long) or areal axis. The present study examined the relationship of locomotor speed to theta indices at CA1 and DG sites across the septotemporal axis as well as in the entorhinal cortex. Our …

Seasonal Hippocampal Plasticity In Food-Storing Birds., David F Sherry, Jennifer S Hoshooley

Psychology Publications

Both food-storing behaviour and the hippocampus change annually in food-storing birds. Food storing increases substantially in autumn and winter in chickadees and tits, jays and nutcrackers and nuthatches. The total size of the chickadee hippocampus increases in autumn and winter as does the rate of hippocampal neurogenesis. The hippocampus is necessary for accurate cache retrieval in food-storing birds and is much larger in food-storing birds than in non-storing passerines. It therefore seems probable that seasonal change in caching and seasonal change in the hippocampus are causally related. The peak in recruitment of new neurons into the hippocampus occurs before birds …

Increased Dendrite Branching In Aβpp/Ps1 Mice And Elongation Of Dendrite Arbors By Fasudil Administration, Brian A. Couch, George J. Demarco, Shannon L. Gourley, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Amyloid-β (Aβ) overproduction and dendrite arbor atrophy are hallmarks of Alzheimer’s disease. The RhoA GTPase (Rho) signals through Rho kinase (ROCK) to control cytoskeletal dynamics and regulate neuron structure. Hyperactive Rho signaling destabilizes neurons leading to dendritic regression that can be rescued by genetic or pharmacological reduction of ROCK signaling. To understand what effect reduced ROCK signaling has on the dendrite arbors of mice that overproduce Aβ, we administered the ROCK inhibitor fasudil to AβPP/PS1 transgenic mice. We report that increased dendrite branching occurs in AβPP/PS1 mice and that fasudil promotes …

Effects Of Hze Irradiation On Chemical Neurotransmission In Rodent Hippocampus, Mayumi Machida

Theses and Dissertations in Biomedical Sciences

Space radiation represents a significant risk to the CNS (central nervous system) during space missions. Most harmful are the HZE (high mass, highly charged (Z), high energy) particles, e.g. ⁵⁶Fe, which possess high ionizing ability, dense energy deposition pattern, and high penetrance.

Accumulating evidence suggests that radiation has significant impact on cognitive functions. In ground-base experiments, HZE radiation induces pronounced deficits in hippocampus dependent learning and memory in rodents. However, the mechanisms underlying these impairments are mostly unknown.

Exposure to HZE radiation elevates the level of oxidation, resulting in cell loss, tissue damage and functional deficits through direct ionization …

Expression Of Nicotinic Acetylcholine Receptor Mrna As A Function Of Age In Whole Hippocampus Preparations From Wistar Rats, Kasey C. Welch

Theses and Dissertations

Whole hippocampus preparations, isolated bilaterally, from untreated Wistar rats at various ages (10-90 days old) were analyzed for the mRNA expression of the alpha 2, alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3, and beta 4 neuronal nicotinic acetylcholine receptor subunits. To do so, RNA was isolated from acutely isolated hippocampal samples, converted to cDNA by means of a reverse transcription reaction, then analyzed with quantitative real-time PCR to determine the relative levels of the mRNAs the cells were expressing at the age when the samples were obtained. The relative expression of the levels of RNA …

Classification Of Neuronal Nicotinic Acetylcholine Receptors In Rat Ca1 Hippocampal Interneuron Subpopulations Defined By Calcium-Binding Protein Mrna Expression, Richard M. Burgon

Theses and Dissertations

In this study, the single-cell relative quantitative mRNA expression of three Calcium-binding proteins (CaBPs; calbindin, calretinin, parvalbumin) and eight nicotinic acetylcholine receptor (nAChR) subunits (alpha2-alpha5, alpha7, beta2-beta4) from interneurons from the stratum radiatum or stratum oriens within the CA1 region of rat hippocampi was analyzed using quantitative real time RT-PCR. Eighty-seven percent of the interneurons examined expressed CaBP mRNA. Parvalbumin mRNA was detected in 64%, while calbindin and calretinin expression was detected in 26% and 40% of interneurons, respectively. CaBP expression was not exclusive; the average number of CaBP mRNA detected per interneuron of the 47 interneurons examined for CaBP …

Estrogen Influences On The Developing Rat Hippocampus Through Interactions With The Brain Derived Neurotrophic Factor And P160 Coactivator Proteins, Derek Tyler Solum

Dissertations

In addition to their primary role in the maintenance and regulation of reproductive capacity, ovarian steroid hormones acting through specific nuclear receptors influence more general neurobiological functions, such as perceptual-spatial skills and learning and memory. Estrogens act to alter certain aspects of cognitive performance and pathology such as epileptic seizure activity and Alzheimer’s disease. Furthermore, ovarian steroids act during development to alter the neuronal cytoarchitecture and synaptic connectivity. These early influences of steroids on the brain are essentially permanent and in part determine the steroid responsiveness of the adult brain. The mechanism and sites of action for the effects of …

Cakß/Pyk2 Kinase Is A Signaling Link For Induction Of Long-Term Potentiation In Ca1 Hippocampus, Yueqiao Huang, Wei-Yang Lu, Declan W. Ali, Kenneth A. Pelkey, Graham M. Pitcher, You Ming Lu, Hiroshi Aoto, John C. Roder, Terukatsu Sasaki, Michael W. Salter

PCOM Scholarly Works

Long-term potentiation (LTP) is an activity-dependent enhancement of synaptic efficacy, considered a model of learning and memory. The biochemical cascade producing LTP requires activation of Src, which upregulates the function of NMDA receptors (NMDARs), but how Src becomes activated is unknown. Here, we show that the focal adhesion kinase CAKß/Pyk2 upregulated NMDAR function by activating Src in CA1 hippocampal neurons. Induction of LTP was prevented by blocking CAKß/Pyk2, and administering CAKß/Pyk2 intracellularly mimicked and occluded LTP. Tyrosine phosphorylation of CAKß/Pyk2 and its association with Src was increased by stimulation that produced LTP. Finally, CAKß/Pyk2-stimulated enhancement of synaptic AMPA responses was …

Prolonged Cyclooxygenase-2 Induction In Neurons And Glia Following Traumatic Brain Injury In The Rat, Kenneth I. Strauss, Mary F. Barbe, Renee Marshall Demarest, Ramesh Raghupathi, Samir Mehta, Raj K. Narayan

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.

Mechanism Of Triazolo-Benzodiazepine And Benzodiazepine Action In Anxiety And Depression: Behavioral Studies With Concomitant In Vivo Ca1 Hippocampal Norepinephrine And Serotonin Release Detection In The Behaving Animal, Patricia A. Broderick, Omotola Hope, Pierrot Jeannot

Publications and Research

1. Real time, in vivo microvoltammetric studies were performed, using miniature carbon-based sensors, to concurrently detect norepinephrine (NE) release and serotonin (5-HT) release, in 2 separate electrochemical signals, within CA₁ region of hippocampus in the freely moving and behaving, male, Sprague Dawley laboratory rat.

2. Concurrently, four parameters of open-field Behavior I.E. Ambulations, Rearing, Fine Movements and Central Ambulatory behavior (a measure of anxiety reduction behavior), were assayed by infrared photobeam detection.

3. Time course studies showed that the mechanism of action of the triazolobenzodiazepine (TBZD), adinazolam, (Deracyn®) is dramatically different from that of the classical benzodiazepine (BZD), diazepam …

The Hippocampus As Episodic Encoder: Does It Play Tag?, Robert H.I. Dale

Scholarship and Professional Work - LAS

Rawlins’s characterization of the hippocampus as a “high-capacity, immediate-term memory store” captures the essential idea in a number of previous models. For example, Gaffan (1974), Gray (1984), Hirsh (1980), Kesner (Bierley, Kesner & Novak 1983), Olton (Olton, Becker & Handelmann 1979), Solomon (1980), and Winocur (1980) all agree that hippocampal animals show memory deficits when required to identify, for whatever reason, one specific event out of a list of recent events. Although these authors disagree on a number of details, Rawlins has identified their models common ground, the core of each model. (It is only fair to note that Gaffan …