Regulation of Dopamine Synaptic Transmission
Our lab examines the neuronal mechanisms controlling the synaptic, cellular and circuit function of the mesolimbic dopamine system. The release of dopamine is a critical component required for learning about rewards in our environment, initiating movements and learning sequences of events. To perform these behaviors, the timing and amount of dopamine released needs to be tightly regulated. We use a combination of electrophysiology, imaging, electrochemisty, and optogenetics to study the neural circuitry controlling the synaptic release of dopamine and examine the disruptions in this system that are thought to underlie psychiatric disorders such as drug addiction and schizophrenia.
Dendro-dentritic dopamine transmission in the VTA
Our first interest examines the synaptic mechanisms that control dopamine transmission in the Ventral Tegmental Area (VTA). Within the cell body region of the VTA dopamine neurons make inhibitory synaptic connections with other dopamine neurons through dendro-dendritic (or dendrite-to-dendrite) type synapses. We are characterizing the mechanisms that regulate the release of dopamine at this synapse and examine how transporters regulate the amount and duration of dopamine following release. The slow synaptic potential (IPSP) that occurs at this synapse is currently the only known direct inhibition mediated by dopamine. By studying this form of transmission we have the opportunity to understand the basic biology that governs dopamine synapses and to understand how drugs of abuse regulate the actions of dopamine.
Mechanisms controlling the release of dopamine from forebrain terminals
Our second interest examines dopamine release in the dorsal striatum and nucleus accumbens. As dopamine neurons release transmitter from axon terminals in the forebrain as well as dendritic terminals in their cell body region, we are especially interested in understanding the factors that may differentially regulate dopamine release from these two different anatomical sites. By comparing the actions of dopamine to other catecholamines we examine how transmission is regulated at synapses that signal through G-protein coupled receptors.
Regulation of dopamine cell excitability
The third area of interest examines how other synaptic inputs regulate the excitability of dopamine cells. 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.
- Courtney NA, AA Mamaligas & CP Ford.Species differences in somatodendritic dopamine transmission determine D2-autoreceptor-mediated inhibition of ventral tegmental area neuron firing. J. Neurosci. 32:13520-8, 2012.
- Ford CP, SC Gantz, PE Phillips & JT Williams.Control of extracellular dopamine at dendrite and axon terminals. J. Neurosci. 30:6975-83, 2010.
- Bender KJ, CP Ford & LO Trussell.Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation. Neuron 68:500-11, 2010.
- Ford CP, PE Phillips & JT Williams.The time course of dopamine transmission in the ventral tegmental area. J. Neurosci. 29:13344-52, 2009.
- Ford CP & JT Williams.Mesoprefrontal dopamine neurons distinguish themselves. Neuron 57:631-2, 2008.