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Impact of High Fat Diet on Central Cardiac Circuits: When The Wanderer is Lost
Cardiac vagal motor drive originates in the brainstem's cardiac vagal motor neurons (CVNs). Despite well-established cardioinhibitory functions in health, our understanding of CVNs in disease is limited. There is a clear connection of cardiovascular regulation with metabolic and energy expenditure systems. Using high fat diet as a model, this talk will explore how metabolic dysfunction impacts the regulation of cardiac tissue through robust inhibition of CVNs. Specifically, it will present an often overlooked modality of inhibition, tonic gamma-aminobuytric acid (GABA) A-type neurotransmission using an array of techniques from single cell patch clamp electrophysiology to transgenic in vivo whole animal physiology. It also will highlight a unique interaction with the delta isoform of protein kinase C to facilitate GABA A-type receptor expression.
Dysfunctional synaptic vesicle recycling – links to epilepsy
Accurate and synchronous neurotransmitter release is essential for brain communication and occurs when neurotransmitter-containing synaptic vesicles (SVs) fuse to release their content in response to neuronal activity. Neurotransmission is sustained by the process of SV recycling, which generates SVs locally at the presynapse. Until relatively recently it was believed that most mutations in genes that were essential for SV recycling would be incompatible with life, due to this fundamental role. However, this is not the case, with mutations in essential genes for SV fusion, retrieval and recycling identified in individuals with epilepsy. This seminar will cover our laboratory’s progress in determining how genetic mutations in people with epilepsy translate into presynaptic dysfunction and ultimately into seizure activity. The principal focus of these studies will be in vitro investigations of, 1) the biological role of these gene products and 2) how their dysfunction impacts SV recycling, using live fluorescence imaging of genetically-encoded reporters. The gene products to be discussed in more detail will be the SV protein SV2A, the protein kinase CDKL5 and the translation repressor FMRP.
The role of protein kinase C gamma in Purkinje cell dendritic development and synapse formation
FENS Forum 2024
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