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Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen
Theses and Dissertations
Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …
A Combinatorial Premotor Neural Code: Transformation Of Sensory Information Into Meaningful Rhythmic Motor Output By A Network Of Heterogeneous Modulatory Neurons, Christopher John Goldsmith
A Combinatorial Premotor Neural Code: Transformation Of Sensory Information Into Meaningful Rhythmic Motor Output By A Network Of Heterogeneous Modulatory Neurons, Christopher John Goldsmith
Theses and Dissertations
The goal of the following research was to investigate the contributions of neural networks in selecting distinct variants of rhythmic motor activity. We used the premotor commissural ganglion (CoG) in the stomatogastric nervous system of the Jonah crab to understand how this network effectively controls the rhythms produced in downstream motor circuits. Prior research determined that individual CoG neurons are necessary to mediate sensory-induced variation in the effected motor patterns. However, single premotor neuron inputs to the STG are not sufficient to recreate the patterns induced by the selective activation of sensory pathways. Thus, it was hypothesized that the CoG-mediated …
The Mechanistic Requirements Of Passive H+ Import Through The Na, K-Atpase, Kevin S. Stanley
The Mechanistic Requirements Of Passive H+ Import Through The Na, K-Atpase, Kevin S. Stanley
Theses and Dissertations
This work focuses on the elucidation of the mechanism of passive proton import through the Na,K-ATPase. This enzyme uses the energy in ATP hydrolysis to exchange three intracellular Na+ for two extracellular K+ to maintain ion gradients within the cell, and while in the absence of physiological external Na+ and K+, the phosphorylated externally open (E2P) conformation passively imports protons, generating an inward current (IH). Chapter one reports on the effects of intracellular cations and nucleotides to shift the Na,K-ATPase into the E2P conformation. We identified that a combination of either internal Na+ and ATP or K+ and Pi. In …
Electrophysiological And Morphological Characterization Of Neurons In The Granular Retrosplenial Cortex, Andrew Nicholas Nye
Electrophysiological And Morphological Characterization Of Neurons In The Granular Retrosplenial Cortex, Andrew Nicholas Nye
Theses and Dissertations
The retrosplenial cortex (RSC) is a centrally located brain region that has reciprocal connections with several brain regions important for memory, including the prefrontal cortex, para-hippocampal region, hippocampal formation, and rhinal cortices. The RSC is also well connected with structures important for sensory processing, including the parietal cortex, thalamus, and visual cortices. Due to this connectivity, and early evidence that suggests the RSC plays a critical role in learning and memory, the region has recently gained much more research attention. Early studies found that patients with brain damage that includes the RSC have difficulty with verbal and visual information, retrieving …
Hydrogen Peroxide And Pharmacological Agent Modulation Of Trpv2 Channel Gating, Tuoxin Cao
Hydrogen Peroxide And Pharmacological Agent Modulation Of Trpv2 Channel Gating, Tuoxin Cao
Theses and Dissertations
Transient receptor potential vanilloid 2 channel (TRPV2) is a Ca2+-permeable ion channel that is highly expressed in leukocytes but is also present in skeletal and cardiac muscle and endocrine cells. The TRPV2 function is implicated in a number of physiological processes, including bacterial phagocytosis, pro-inflammatory cytokine production, cardiac hypertrophy, and cancer development. TRPV2 knockout mice exhibit a high incidence of perinatal mortality, arguing that the channel plays essential roles in physiology. Despite the importance of TRPV2 for normal homeostasis, the mechanisms that control TRPV2 gating in response to pharmacological agonists, heating, membrane stretch, bioactive lipids and reactive oxygen …
Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed
Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed
Theses and Dissertations
GABA neurons in the ventral tegmental area of the midbrain are important components in the brain's reward circuit. Long term changes in this circuit occur through the process of synaptic plasticity. It has been shown that high frequency stimulation, as well as treatment with endocannabinoids, can cause GABA neurons in the ventral tegmental area to undergo long term depression, a form of synaptic plasticity that decreases excitability of cells. The present study elaborates on the mechanism whereby high frequency stimulation can result in long term depression of ventral tegmental area GABA neurons. Using the whole cell patch clamp technique in …
Sphingosine-1-Phosphate And Fingolimod (Fty720) Regulate Icl,Swell In Hl-1 Cardiac Myocytes Via Intracellular Binding And Mitochondrial Ros Production, Pooja Desai
Theses and Dissertations
Swelling-activated Cl− current (ICl,swell) is an outwardly-rectifying current that plays an important role in cardiac electrical activity, cellular volume regulation, apoptosis, and acts as a potential effector of mechanoelectrical feedback. Persistent activation of ICl,swell has been observed in models of cardiovascular disease. We previously suggested sphingosine-1-phosphate (S1P) activates volume-sensitive Cl- current (ICl,swell) by ROS-dependent signaling. S1P and its analog, FTY720 (fingolimod), primarily act via G-protein coupled receptors (S1PR; S1PR1-3 in heart), but several intracellular S1P ligands are known. We investigated how these agents regulate ICl,swell. ICl,swell was elicited by bath S1P (500 nM), FTY720 (S1PR1,3 agonist; 10 μM), and SEW2871 …
Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval
Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval
Theses and Dissertations
Dopamine cells within the ventral tegmental area of the brain are involved in motivation and reward. Drugs of abuse target these dopamine cells altering their activity and plasticity resulting in addiction. While dopamine cell activity is primarily involved in addiction, the GABA neurons in the VTA have also been shown to have an indirect role. By decreasing the activity of the inhibitory GABA inputs onto dopamine neurons abusive drugs can indirectly increase dopamine cell activity resulting in addictive behaviors. However, although GABA neurons are important in the perception of reward, much less is known about how the excitatory inputs to …
Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan
Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan
Theses and Dissertations
Heterotrimeric guanine nucleotide-binding proteins (G-proteins) consist of an alpha subunit (Gα) and the dimeric beta-gamma subunit (Gβγ). The first example of direct cell signaling by Gβγ was the discovery of its role in activating G-protein regulated inwardly rectifying K+ (GIRK) channels which underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate. Published crystal structures have provided important insights into the structures of the G-protein subunits and GIRK channels separately, but co-crystals of the channel and Gβγ together remain elusive and no specific reciprocal residue interactions between the two proteins are currently known. Given the absence of direct …