SINTN Stanford Institute for Neuro-Innovation & Translational Neurosciences

The Stanford Neurosciences Institute
proudly announces a research seminar by

Anatol Kreitzer

"Mechanisms of Motor Control and Reinforcement in the Basal Ganglia"

December 13th, 2012 - 4:30 - Clark Auditorium

Anatol Kreitzer Ph.D.
Assistant Investigator,
Gladstone Institute of Neurological Disease
Assistant Professor,
Depts. of Physiology and Neurology, UCSF

Website: Kreitzer lab Web Site

A conversation with Anatol Kreitzer with the Stanford group Neuwrite West can be streamed or downloaded here: Kreitzer conversation


Abstract:

Neural circuits of the basal ganglia are critical for adaptive motor learning. Two parallel basal ganglia pathways have been described, which are proposed to exert opposing influences on motor function. According to this classical model, activation of the direct pathway facilitates movements/actions and activation of the indirect pathway inhibits movements/actions. To test and extend this model, we directly activated basal ganglia circuitry in vivo, using optogenetic control of direct- and indirect-pathway medium spiny projection neurons (MSNs), achieved through Cre-dependent viral expression of channelrhodopsin-2 in the striatum of D1-Cre and D2-Cre BAC transgenic mice. Activation of direct- or indirect-pathway basal ganglia circuits yielded distinct motor behaviors, reminiscent of hyper- or hypo-dopaminergic states. In an operant self-stimulation paradigm, direct pathway activation reinforced operant responding, while stimulation of D2-expressing neurons was punishing, demonstrating that direct activation of these circuits is sufficient to modify the probability of performing future actions. Using brain slice physiology, we are now beginning to address the synaptic basis for regulation of direct and indirect pathway activity during learning.

Recent Papers:

[1] Kravitz AV, Tye LD, Kreitzer AC (2012). Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nature Neuroscience 15: 816–818

[2] Lerner TN, Kreitzer AC (2012). RGS4 is required for dopaminergic control of striatal LTD and susceptibility to parkinsonian motor deficits. Neuron 73:347-359

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