The Cellular Regulation of Dopamine-Dependent Behaviors
Welcome to Dr. Art Riegel's Laboratory on the Cellular Regulation of Dopamine-Dependent Behaviors.
In nature, environmental reinforcers elicit approach behaviors that are evolutionarily advantageous to the organism. These biological mechanisms help the organism define the nature of its environment by learning to distinguish between potentially helpful and harmful stimuli. Dopamine neurons originating from the ventral tegmental area and substantia nigra serve important roles in behavior, as well as cognition, motor activity, motivation, attention, learning and reward. The presentation of unexpected rewards stimulates a transient release of dopamine from terminals, which may encode a teaching signal. This increase in dopamine release is initiated by a burst-pause firing pattern of the neuron, which in turn is supported in part by potassium channels located on dopamine neuron dendrites. These channels include both GIRK (G-protein coupled inwardly rectifying potassium) and sK (calcium activated potassium) channels. GIRK and sK channels are the effectors of important G protein coupled receptors including GABA, acetylcholine, norepinephrine, and glutamate. The sensitivity to such neurotransmitters is regulated by the co-release of neuropeptides, including endogenous opioids, endocannabinoids and corticotropin releasing factor (CRF), which are believed to be important for tuning behavioral sensitivity to arousal, avoidance and stress.
Studies in our laboratory currently investigate how these different neurotransmitters and neuroregulators modulate the excitability of dopamine neurons and the release of dopamine from nerve terminals. The experimental procedures incorporate behavioral self-administration of drugs of abuse and brain slice electrophysiology (whole cell patch clamp) in conjunction with calcium imaging (multi photon), optogenetics and intracellular uncaging (flash photolysis). These studies are predicted to provide a basis to better understand the cellular mechanisms regulating dopamine neuron excitability during normal and abnormal brain function.