Neuroscience and Neurobiology Commons^™

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Non-Canonical Activation Of Nrf2 By Dimercaptopropanol As A Treatment For Huntington's Disease, Margaret Lauren Tindale

Electronic Thesis and Dissertation Repository

Mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels are strongly implicated in various neurodegenerative disorders, including Huntington’s disease (HD). Expression of the mutant Huntingtin protein (mHTT) containing an expanded polyglutamine repeat is associated with oxidative stress and toxicity in striatal neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for regulating expression of a diverse array of antioxidant and cytoprotective genes. Most known Nrf2-activating compounds act through the canonical pathway by mimicking a transient oxidative insult, and treatment effects are short-lived. This study reveals an increase in striatal cell viability, and a reduction in …

Mechanisms Of Neuroprotection Against Ischemic Insult By Stress-Inducible Phosphoprotein-1, Jason Xu

Electronic Thesis and Dissertation Repository

Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrP^C) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrP^C, α7nAChR, and ALK2 prior to oxygen-glucose deprivation …

Developing A Contrast Agent For The In Vivo Detection Of Apoptosis, Mary R. Cobb

Electronic Thesis and Dissertation Repository

Currently, there is no way to assess apoptotic cell death in living organisms. We have developed a novel contrast agent targeted toward the detection of caspase-3 activity, the key enzymatic mediator of apoptosis. Our contrast agent consists of a dual magnetic resonance imaging/fluorescent probe coupled to a cell penetrating peptide (CPP) sequence by a peptide backbone containing a caspase-3 cleavage site. The CPP allows the agent to cross cell membranes and the blood brain barrier. In cells undergoing apoptosis, activated caspase-3 will cleave the agent removing the CPP and trapping the imaging probes inside the cell.

The purpose of this …

Muscarinic Attenuation Of Mnemonic Rule Representation In Macaque Dorsolateral Prefrontal Cortex During A Pro- And Anti-Saccade Task, Alex J. Major

Electronic Thesis and Dissertation Repository

Maintenance of context is necessary for execution of appropriate responses to diverse environmental stimuli. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in executive function, including working memory and representation of abstract rules, and is modulated by the ascending cholinergic system through nicotinic and muscarinic receptors. Muscarinic receptors’ effect on local primate DLPFC neural activity in vivo during cognitive tasks remains poorly understood. Here we examined the effects of muscarinic receptor blockade on rule-related activity in the macaque prefrontal cortex by combining iontophoretic application of the general muscarinic receptor antagonist scopolamine with single-unit recordings while monkeys performed a rule-guided …

Modulation Of Synaptic Plasticity By Hippocampal Theta Rhythm, Clayton Law

Electronic Thesis and Dissertation Repository

The hippocampal theta rhythm facilitates memory formation. This study investigated the temporal relation of long-term potentiation (LTP) with the hippocampal theta rhythm. Theta rhythm consists of a wave of somatodendritic depolarization, but the depolarization of apical and basal dendrites of hippocampal CA1 pyramidal cells peak at a similar theta phase. Thus, we hypothesize that the population spike excitability evoked by excitation of the apical and basal dendrites peak at a similar phase of the theta rhythm. We also expect that LTP at the basal and apical dendritic synapses to be maximal at a similar theta phase.

Rats (~300 g) were …

Abnormal Hippocampal Activation In Freely Behaving Mice Deficient For The Vesicular Acetylcholine Transporter, Shahin Moallem

Electronic Thesis and Dissertation Repository

Acetylcholine (Ach) has a fundamental role in cortical activation. The activation of the hippocampus, a cortex implicated in cognitive and sensorimotor functions, is characterized by an increase in power and frequency of oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range. We studied hippocampal activation in two mutant mouse lines with deficiency in cholinergic functionality: VAChT KD^HET (HET), and VAChT^{Nkx2.1-Cre-flox/flox} (KO). We hypothesized that the mutant mice, relative to wild-type (WT) mice, will manifest abnormal theta and gamma oscillations during different behaviors, and in response to muscarinic cholinergic antagonist scopolamine hydrochloride and to the NMDA …

Mechanisms Of Neural Precursor Cell Apoptosis By Microglia-Derived Cytokines, Jennifer Guadagno

Electronic Thesis and Dissertation Repository

The persistence of neural precursor cells (NPCs) in distinct niches of the adult brain and spinal cord provides an important opportunity for regeneration in the affected nervous system. In the adult brain, neural precursor cells (NPCs) generate new neurons that can be integrated into the CNS circuitry to replace damaged or lost neurons, and contribute to learning and memory processes. Deregulated neurogenesis has been observed under both acute and chronic neurological conditions including stroke, Alzheimer’s disease, and Parkinson’s disease. The extent to which neurogenesis contributes to brain repair is severely limited by the neuroinflammatory processes associated with these neurodegenerative conditions. …