Neuroscience and Neurobiology Commons^™

Mechanistic Insight Into Traumatic Brain Injury Induced Neuronal Membrane Disruption: Cathepsin B Relocalization And A Neun Negative Cortical Neuron Subpopulation, Martina L. Hernandez

Theses and Dissertations

Traumatic brain injury (TBI) is a mechanical insult to the head that leads to brain damage and, in turn, causes long-term sensory, motor, cognitive, and affective dysfunction. Diffuse pathologies seen following such injury are associated with these life-altering outcomes that impact the daily lives of TBI survivors. The diffuse pathology that this body of work focuses on is neuronal membrane disruption; it is characterized by increased permeability of the neuron’s plasma membrane. Moreover, our lab had previously found that membrane disruption is exacerbated with intracranial pressure (ICP) elevation. We set out to measure the duration of membrane disruption following injury …

Regaining Effort-Based Food Motivation: The Drug Methylphenidate Reverses The Depressive Effects Of Tetrabenazine In Female Rats, Deanna Pietrorazio

Honors Scholar Theses

Tetrabenazine (TBZ), a vesicular monoamine transporter type 2 (VMAT-2) inhibitor, depletes dopamine and induces motivational deficits and other depressive symptoms in humans. Methylphenidate (MPH) is a dopamine transport blocker that is used to enhance motivational function. Previous studies have shown that in male rats, TBZ induces a shift in effort-related choice such that a low-effort bias is induced. In male rats this occurs at a dose range of 0.75-1.0 mg/kg TBZ, and this effect is reversible with co-administration of MPH. Recent studies have shown that females need a higher dose of TBZ (2.0 mg/kg) to show the low-effort bias. The …

Neuroactivational And Behavioral Correlates Of Psychosocial Stress-Induced Cocaine Seeking In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Stephany J. Mcdonald, Samantha De Guzman, Nicole E. Hubbard, Colin M. Kulick-Soper, Jessica J. Debski, Bianca Patel, Daniel Manvich

Rowan-Virtua Research Day

A prominent feature of cocaine abuse is a high risk of relapse even despite prolonged periods of abstinence. Psychosocial stress is thought to be a major contributor to the onset of cocaine craving and relapse in human substance abusers, yet most preclinical models of stress-induced relapse employ physical stressors (e.g., unpredictable footshock) or pharmacological stressors (e.g., yohimbine to elicit a drug seeking response) and do not rely upon psychosocial stress per se. Importantly, social stressors are well known to activate distinct neural circuits within the brain as compared to other stressors. It is therefore possible that currently available animal models …

Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna

Graduate School of Biomedical Sciences Theses and Dissertations

Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …

Effects Of Repeated Intermittent Episodes Of Social Stress On The Acquisition And Extinction Of A Reward-Seeking Task, Nikki Sullivan

Honors Theses

Repeated exposure to stress is known to have a myriad of effects on the brain, contributing to the development of psychiatric disorders, such as anxiety, depression, and drug addiction. For example, rats undergoing repeated social stress develop increased cocaine self-administration. These effects of stress are not well-understood and are related to changes in the brain reward system. This study investigated the effects of repeated social stress on reward-seeking behavior via the acquisition and extinction of a discriminative stimulus (DS) task and on anxiety-like behavior in the elevated plus maze (EPM). Male rats underwent intermittent social defeat (4 sessions in 10 …

Influences Of Salvinorin A And Sex Differences On Depressive- And Anxiety-Like Behaviors In A Chronic Mild Stress Paradigm, Sarah Mitchell

Theses

Kappa opioid receptors are colocalized with dopamine receptors and are frequently associated with depression, anxiety, stress, and drug use and abuse. KOR antagonism has widely been considered anti-depressive and anxiolytic in animal models while agonism is pro-depressive and anxiogenic. However, recent findings suggest that SalvA, a natural kappa agonist derived from a plant in the mint family, can reduce depressive- and anxiety-like behavior in rats. The current study investigated the effects of chronic mild stress on behavior, attenuation by SalvA, and sex differences. 52 Long-Evans rats, 26 males and 26 females, were exposed to six weeks of CMS. Animals received …

Altered Gating Of KV1.4 In The Nucleus Accumbens Suppresses Motivation For Reward, Bernadette O'Donovan, Adewale Adeluyi, Erin L Anderson, Robert D. Cole, Jill R. Turner, Pavel I. Ortinski

Neuroscience Faculty Publications

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine …

No Evidence That Portion Size Influences Food Consumption In Male Sprague Dawley Rats, Fabien Naniex, Sophie C. Pinder, Megan Y. Summers, Renee M. Rouleau, Eric Robinson, Kevin P. Myers, James E. Mccutcheon

Faculty Journal Articles

In studies of eating behavior that have been conducted in humans, the tendency to consume more when given larger portions of food, known as the portion size effect (PSE), is one of the most robust and widely replicated findings. Despite this, the mechanisms that underpin it are still unknown. In particular, it is unclear whether the PSE arises from higher-order social and cognitive processes that are unique to humans or, instead, reflects more fundamental processes that drive feeding, such as conditioned food-seeking. Importantly, studies in rodents and other animals have yet to show convincing evidence of a PSE. In this …

The Role Of Progesterone Receptor In The Developing Medial Preoptic Nucleus, Diana Lalitsasivimol

Legacy Theses & Dissertations (2009 - 2024)

Numerous neurodevelopmental and neuropsychiatric diseases have a distinct sex bias in

Developmental Changes In The Activation And Structure Of The Contextual Fear Neural Circuit From Infancy To Adulthood, Anthony John Santarelli

Legacy Theses & Dissertations (2009 - 2024)

The contextual fear circuit, centered on the basolateral nucleus of the amygdala (BLA), is comprised of projections from the hippocampal formation and prefrontal cortex, and mediates an animals ability to learn and predict associations between the environment and biologically relevant stimuli. While the function and structure of this circuit has been well characterized in adult species, relatively little is known about its development as an animal transitions from infancy to adulthood. Recent evidence has begun to suggest that infants, juveniles, and adolescents may show remarkable heterogeneity in the behavioral, activational, and structural properties of the circuit. In this thesis, I …

Inactivation Of The Medial-Prefrontal Cortex Impairs Interval Timing Precision, But Not Timing Accuracy Or Scalar Timing In A Peak-Interval Procedure In Rats, Catalin V. Buhusi, Marcelo B. Reyes, Cody-Aaron Gathers, Sorinel A. Oprisan, Mona Buhusi

Psychology Faculty Publications

Motor sequence learning, planning and execution of goal-directed behaviors, and decision making rely on accurate time estimation and production of durations in the seconds-to-minutes range. The pathways involved in planning and execution of goal-directed behaviors include cortico-striato-thalamo-cortical circuitry modulated by dopaminergic inputs. A critical feature of interval timing is its scalar property, by which the precision of timing is proportional to the timed duration. We examined the role of medial prefrontal cortex (mPFC) in timing by evaluating the effect of its reversible inactivation on timing accuracy, timing precision and scalar timing. Rats were trained to time two durations in a …

Investigating The Effects Of Sensory Learning In Rats Using Intra And Extra Stimulus Modalities, Ariel M. Kershner

Faculty Curated Undergraduate Works

The purpose of this study was to see what rats learn about the elements of a compound stimulus (a stimulus composed of two different stimuli), and whether their learning differs if the compound is from the same modality (intra-modal), i.e. both visual, or from different modalities (inter-modal), i.e. visual and auditory. We hypothesized that the rats would respond more to the compound stimuli than to the single stimuli (Pearce and Wilson, 1990), more to the compound modality of inter-modal elements than to the compound modality of intra-modal elements (Miller, 1971 and Gingras, 2009), equally to the intra-modal elements (Rescorla, 1972), …

Nmda Receptor Blockade Specifically Impedes The Acquisition Of Incentive Salience Attribution, Jonathan J. Chow, Joshua S. Beckmann

Psychology Faculty Publications

Glutamatergic signaling plays an important role in learning and memory. Using Pavlovian conditioned approach procedures, the mechanisms that drive stimulus-reward learning and memory have been investigated. However, there are instances where reward-predictive stimuli can function beyond being solely predictive and can be attributed with “motivational value” or incentive salience. Using a Pavlovian conditioned approach procedure consisting of two different but equally predictive stimuli (lever vs. tone) we investigated the role NMDA receptor function has in the attribution of incentive salience. The results revealed that the administration of MK-801, an NMDA receptor antagonist, during acquisition of Pavlovian conditioned approach promoted goal-tracking …

Human-Like Behavior And Cognition: Not A Good Starting Point, Magnus Helgheim Blystad

Animal Sentience

Chapman & Huffman make use of observations and studies that show how humans may not be as unique in our behaviour and cognition as previously thought. I wholeheartedly agree that our uniqueness might be small and that if it exists, it should not give our species any right to act cruelly towards other animals. However, this kind of logic can be problematic. I present a few of the issues in this commentary.

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 …

Disruption Of Hippocampal Multisynaptic Networks By General Anesthetics., Min-Ching Kuo, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

METHODS: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

RESULTS: Monosynaptic population excitatory postsynaptic potentials at the …

Reduced Ability Of Calcitriol To Promote Augmented Dopamine Release In The Lesioned Striatum Of Aged Rats, Wayne A. Cass, Laura E. Peters

Neuroscience Faculty Publications

Parkinson’s disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats. Animals were given a single injection of 12 μg 6-OHDA into the right striatum. Four weeks later they were …

Transcriptional Signatures Of Brain Aging And Alzheimer's Disease: What Are Our Rodent Models Telling Us?, Kendra E. Hargis, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

Aging is the biggest risk factor for idiopathic Alzheimer’s disease (AD). Recently, the National Institutes of Health released AD research recommendations that include: appreciating normal brain aging, expanding data-driven research, using open-access resources, and evaluating experimental reproducibility. Transcriptome data sets for aging and AD in humans and animal models are available in NIH-curated, publically accessible databases. However, little work has been done to test for concordance among those molecular signatures. Here, we test the hypothesis that brain transcriptional profiles from animal models recapitulate those observed in the human condition. Raw transcriptional profile data from twenty-nine studies were analyzed to produce …

The Effect Of Sazetidine-A And Other Nicotinic Ligands On Nicotine Controlled Goal-Tracking In Female And Male Rats, S. Charntikov, A. M. Falco, K. Fink, Linda P. Dwoskin, R. A. Bevins

Pharmaceutical Sciences Faculty Publications

Nicotine is the primary addictive component of tobacco products and its complex stimulus effects are readily discriminated by humans and non-human animals. Previous preclinical research investigating directly the nature of the nicotine stimulus has been limited to male rodents. The current study began to address this significant gap in the literature by training female and male rats to discriminate 0.4 mg/kg nicotine from saline in the discriminated goal-tracking task. In this task, access to sucrose was intermittently available on nicotine session. On saline session, intermixed with nicotine sessions on separate days, sucrose was not available. Both sexes acquired the discrimination …

Tribute To Jaak Panksepp, Jonathan Balcombe

Animal Sentience

No abstract provided.

Associative Spike Timing-Dependent Potentiation Of The Basal Dendritic Excitatory Synapses In The Hippocampus In Vivo., Thomas K Fung, Clayton S Law, L Stan Leung

Physiology and Pharmacology Publications

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of -10 …

Examination Of Methamphetamine Reinstatement In Female And Male Rats: A Pre-Clinical Model Of Relapse, Steven T. Pittenger

Department of Psychology: Dissertations, Theses, and Student Research

Methamphetamine (meth) dependence is often characterized by persistent and chronic relapse (i.e., return to drug use). There is growing pre-clinical and human evidence suggesting females are at greater risk to relapse. The set of studies presented in this dissertation extended this limited evidence by identifying sex-dependent neural substrates correlated with meth-triggered reinstatement (Experiment 1) and by examining sex-differences in reinstatement triggered by drugs of abuse that are commonly co-abused with meth (Experiment 2). Female and male rats were trained to self-administer meth, received subsequent extinction sessions, and then tested for reinstatement. In Experiment 1, rats were perfused following reinstatement testing …

The Tnfα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss, L. Creed Pettigrew, Richard J. Kryscio, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from …

The Effects Of Body Weight, Food Intake, Activity, And Anxiety In Female Rats, Rachel Mangan

Senior Honors Projects

Zolpidem is a nonbenzodiazepine sedative-hypnotic drug. It is placed in the imidazopyridine class of drugs, which are gamma aminobutyric acis (GABA)-A receptor agonists due to their effect on the alpha-1 GABA-A receptor subunit. The present study focused on differences observed during administration of zolpidem to female rats as compared to a previous study performed on male rats. Female rats receiving zolpidem did not differ significantly from those rats not receiving zolpidem; whereas, male animals were shown to be more affected by zolpidem causing increased food intake, lowered activity levels, increased anxiety, and increased visceral adiposity. Female rats exhibited little change …

The Effects Of The Ketogenic Diet (Kd) On Inflammatory Pain, Livia S. Wyss

Senior Theses and Projects

BACKGROUND: Pain is the most common ailment around the world, according to the American Academy of Pain Medicine; 100 million Americans suffer with chronic pain, which is more than any other main disorder and is described by more than 60% as impacted their overall enjoyment of life (AAPA). The ketogenic diet (KD) is a high fat, low carbohydrate dietary regimen, which is described to decrease neuronal excitation, increase ketone bodies and ATP levels, while lowering glucose and proinflammatory cytokines. The KD is an effective therapy for epilepsy; a disorder that arises from either lowered inhibition or increased excitation, similar to …

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …

Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate …

Sleep Deprivation And Voluntary Alcohol Consumption In Adolescent Rats, Sancho N. Sequeira

Masters Theses, 2010-2019

Alcohol is one of the most common psychoactive drugs, and has been used by humans for thousands of years. Research has focused on the effects of alcohol on sleep, however recent trends in the literature have taken a more bidirectional approach to the relationship between alcohol and sleep. This research investigates the effects of chronic, partial sleep deprivation on alcohol consumption. Twelve adolescent Sprague Dawley rats had free access to two bottles at all times, one containing water and one containing a 7% alcohol and water solution. Sleep deprivation was achieved by using a forced exercise wheel. All rats were …

Comparison Between Coated Vs. Uncoated Suture Middle Cerebral Artery Occlusion In The Rat As Assessed By Perfusion/Diffusion Weighted Imaging, James Bouley, Marc Fisher, Nils Henninger

Nils Henninger

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated …

Characterizing Tissue Fate After Transient Cerebral Ischemia Of Varying Duration Using Quantitative Diffusion And Perfusion Imaging, Juergen Bardutzky, Qiang Shen, Nils Henninger, Stefan Schwab, Timothy Duong, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of reperfusion on ischemic lesion evolution and pixel-by-pixel apparent diffusion coefficient-cerebral blood flow (ADC-CBF) dynamics of core and mismatch tissues after 35, 60, and 95 minutes of transient focal ischemia in rats (n=28). METHODS: Serial diffusion-, perfusion-, and T2-weighted imaging were performed up to 24 hours. The evolution of the magnetic resonance image-derived lesion volume was investigated and ADC-CBF scatterplots were performed to prospectively characterize the ADC and CBF dynamics of core and mismatch tissues with different fates. For comparison, similar analysis was performed on a historical …