Our lab examines the neuronal mechanism by which G-protein coupled receptors (GPCRs) mediate synaptic transmission in the mesolimbic and striatonigral systems. Neuromodulators such as dopamine, acetylcholine and serotonin play key roles in controlling a variety of motivated behaviors including decision-making, action selection, motor skill learning, habit formation and reward processing. We use a combination of electrophysiology, imaging, electrochemisty, and optogenetics to study how the synaptic release of these transmitters becomes encoded within mesolimbic and striatonigral circuits through their GPCRs. By identifying the mechanisms regulating metobotropic transmission we aim to identify the disruptions in these system that are thought to underlie psychiatric disorders such as drug addiction and schizophrenia.
A major interest of the lab examines the mechanisms that control dopamine signaling and the synaptic activation of D2-receptors. We are interested in understanding the spatial and temporal dynamics governing dopamine transmission. Our work examines how transporters gate the spillover of dopamine to determine how drugs of abuse like cocaine block reuptake to alter transmission at synapses within the striatum, nucleus accumbens and ventral tegmental area. By studying synaptic potentials mediated by D2-receptors we have the opportunity to understand the basic biology that governs dopamine synapses and mechanisms by which drugs of abuse alter the synaptic actions of dopamine.
A second area of interest examines how the release of acetylcholine from cholinergic interneurons in the dorsal striatum is encoded through muscarinic receptors. Like dopamine, cholinergic transmission is involved in multiple basal ganglia based functions and dysfunctions in acetylcholine signaling are associated with a variety of neurological movement disorders including Parkinson’s disease, Huntington’s disease, and dystonia. We examine the dynamics and modulation of acetylcholine release at muscarinic synapses onto direct pathway medium spiny neurons using the combination of viral-mediated gene delivery, optogenetics and electrophysiology to understand how cholinergic signals regulate striatal circuit activity.
Other projects examine how synaptic inputs regulate the excitability of dopamine neurons in the VTA. Inhibitory and excitatory synaptic inputs are important regulators of dopamine cell excitability. These inputs control the baseline firing of dopamine cells and drive bursting activity. All known drugs of abuse (ranging from cocaine and morphine to alcohol and nicotine) stimulate the release of dopamine. The strength of these synaptic inputs becomes potentiated following administration of drugs of abuse. This is thought to be one of the initial triggers that may initiate and/or underlie addiction. Our work aims to understand the basic physiology by which these synaptic inputs regulate dopamine cell firing with the long-term goal being to understand the underlying alterations that result from drug abuse.
|First Name||Last Name||Middle Initial||Degree||Position|
|Michael||Grybko||BS||Professional Research Assistant|
|Cam||Waschke||PhD||Professional Research Assistant|