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.
Dopamine transmission and signaling through D2-receptors
A major interest of the lab examines the mechanisms 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 within reward circuitry of the brain. By studying synaptic potentials mediated by D2-receptors in the VTA and striatum 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.
Regulation of dopamine neuron excitability
A second area of interest examines 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.
Differences in transmission among catecholamines
Other projects examine the cellular excitability and synaptic regulation of serotonergic neurons in the dorsal raphe and noradrenaline neurons in the locus coeruleus. Localized to relatively small populations of neurons in the brain, these transmitters play a major role in regulating diverse behaviors including mood, attention, stress and anxiety. By comparing different populations of catecholamine neurons we aim to understand the general principles by which these neuromodulators signal at their GPCR synapses.
- McCall JG, R Al-Hasani, ER Siuda, DY Hong, AJ Norris, CP Ford & MR Bruchas. CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety. Neuron 87:605-20, 2015.
- Piccart E, Courtney NA, Branch SY, CP Ford, Beckstead MJ. Neurotensin induces presynaptic depression of D2 dopamine autoreceptor-mediated transmission in midbrain dopaminergic neurons. J. Neurosci. 35: 11144-11152, 2015.
- Marcott PF, Mamaligas AA & CP Ford. Phasic Dopamine Release Drives Rapid Activation of Striatal D2-Receptors. Neuron. 84:1-13, 2014.
- Courtney NA & CP Ford. The timing of dopamine- and noradrenaline-mediated transmission reflects underlying differences in the extent of spillover and pooling. J. Neurosci. 34:7645-56, 2014.
- Ford CP. The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience 282:13-22, (review), 2014.
- Courtney NA, Mamaligas AA & 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.