Life Sciences Commons^™

The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger

Arts & Sciences Electronic Theses and Dissertations

Brain extracellular concentration of the peptide amyloid-β (Aβ) is a major contributor to Alzheimer’s disease (AD) pathogenesis. High Aβ levels in the extracellular space precipitate aggregation of the peptide into soluble and insoluble toxic species. This process begins decades before cognitive impairment and triggers the cascade of pathology that eventually leads to AD. Synaptic activity is key to the regulation of extracellular Aβ levels. Presynaptic activity drives the production of Aβ, while postsynaptic receptor activation exhibits more nuanced regulation. For example, high levels of NMDA receptor (NMDA-R) activation have been shown to decrease Aβ production through the extracellular signal-regulated kinase …

The Role Of Glutamate Neurotransmission In The Ventral Tegmental Area In The Expression Of Conditioned Approach Learning, Priscila Hachimine-Merli

Dissertations, Theses, and Capstone Projects

Conditioned stimuli (CSs) come to function as CSs by acquiring the capacity to activate the same mesocorticolimbic dopamine (DA) neurons activated by primary rewards, producing conditioned activation of these neurons and their associated motivational states. This model stipulates that CSs activate mesocorticolimbic DA systems through the activation of glutamate receptors on DA neurons in the ventral tegmental area (VTA). We tested the hypothesis that glutamate receptor stimulation in the VTA is necessary for the expression of conditioned approach. Rats were tested in a conditioned approach protocol that consisted of 7 consecutive conditioning sessions (light presentations and food were paired), one …

The Nucleus Accumbens Core Dopamine D1 And Glutamate Ampa/Nmda Receptors Play A Transient Role In The Performance Of Pavlovian Approach Behavior, Veronica Dobrovitsky

Dissertations, Theses, and Capstone Projects

The role of the nucleus accumbens core (NAc core) continues to be redefined with newly acquired data on neurochemical mechanisms mediating the learning and performance of behavior. Previous empirical data showed that dopamine transmission at the D1 receptor (D1R) plays a transient role in the expression of learned Pavlovian approach behavior. Here we show that, prior to overtraining, dopamine activity at D1Rs specifically within the NAc core is critical for the performance of approach behavior elicited by the recently-acquired reward-paired cue. Blockade of D1Rs in the NAc core, but not the dorsomedial striatum or NAc shell, disrupted approach responses during …

Mechanisms Underlying Executive Function Deficits, Sagar Jayawantrao Desai

Electronic Thesis and Dissertation Repository

In our daily life, we come across situations where we meet unanticipated challenges, we must take certain decisions, pay attention, be flexible and inhibit impulsive actions to achieve goal directed behaviour. During these processes, we unknowingly use sets of interdependent cognitive processes collectively called ‘executive function’. Executive function is mainly regulated by the frontal lobe. Impaired executive function is associated with disorders such as schizophrenia, Alzheimer’s disease, autism and attention deficit hyperactivity disorder (ADHD).

In this thesis, we investigated neurotransmitters and interactions among them regulating executive function. Further, we investigated mechanisms underlying those interactions mediating executive function in rats using …

Calcineurin/Nfat Signaling In Activated Astrocytes Drives Network Hyperexcitability In AΒ-Bearing Mice, Pradoldej Sompol, Jennifer L. Furman, Melanie M. Pleiss, Susan D. Kraner, Irina A. Artiushin, Seth R. Batten, Jorge E. Quintero, Linda A. Simmerman, Tina L. Beckett, Mark A. Lovell, M. Paul Murphy, Greg A. Gerhardt, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Hyperexcitable neuronal networks are mechanistically linked to the pathologic and clinical features of Alzheimer's disease (AD). Astrocytes are a primary defense against hyperexcitability, but their functional phenotype during AD is poorly understood. Here, we found that activated astrocytes in the 5xFAD mouse model were strongly associated with proteolysis of the protein phosphatase calcineurin (CN) and the elevated expression of the CN-dependent transcription factor nuclear factor of activated T cells 4 (NFAT4). Intrahippocampal injections of adeno-associated virus vectors containing the astrocyte-specific promoter Gfa2 and the NFAT inhibitory peptide VIVIT reduced signs of glutamate-mediated hyperexcitability in 5xFAD mice, measured in vivo with …

Using Enzyme-Based Biosensors To Measure Tonic And Phasic Glutamate In Alzheimer's Mouse Models, Holly C. Hunsberger, Sharay E. Setti, Ryan T. Heslin, Jorge E. Quintero, Greg A. Gerhardt, Miranda N. Reed

Neuroscience Faculty Publications

Neurotransmitter disruption is often a key component of diseases of the central nervous system (CNS), playing a role in the pathology underlying Alzheimer's disease, Parkinson's disease, depression, and anxiety. Traditionally, microdialysis has been the most common (lauded) technique to examine neurotransmitter changes that occur in these disorders. But because microdialysis has the ability to measure slow 1-20 minute changes across large areas of tissue, it has the disadvantage of invasiveness, potentially destroying intrinsic connections within the brain and a slow sampling capability. A relatively newer technique, the microelectrode array (MEA), has numerous advantages for measuring specific neurotransmitter changes within discrete …

Major Neurotransmitters In The Brain, Amy S. Yu '17

Independent Study

Arguably the most important and powerful organ in the human body, the brain controls virtually everything one does. From chewing gum to running a marathon, the brain dictates one’s physical responses and actions, while also mediating learning, memory, and emotions. These functions are all regulated by neurotransmitter activity in the brain. While the brain works in complex ways, recent discoveries about neurotransmitters allow us to better understand the underlying mechanisms of brain operation. Each neurotransmitter fulfills a distinct role, but they rely on one another to perform certain activities in the brain as well. The purpose of this review is …

A Novel Educational Module To Teach Neural Circuits For College And High School Students: Ngss-Neurons, Genetics, And Selective Stimulations, Zana R. Majeed, Felicitas Koch, Joshua Morgan, Heidi Anderson, Jennifer Wilson, Robin L. Cooper

Biology Faculty Publications

This report introduces various approaches to target defined neural pathways for stimulation and to address the effect of particular neural circuits on behavior in a model animal, the fruit fly (Drosophila melanogaster). The objective of this novel educational module described can be used to explain and address principle concepts in neurobiology for high school and college level students. A goal of neurobiology is to show how neural circuit activity controls corresponding behavior in animals. The fruit fly model system provides powerful genetic tools, such as the UAS-Gal4 system, to manipulate expression of non-native proteins in various populations of …