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Neuroscience Graduate Program at UCSF

Faculty - Joshua Berke, Ph.D.

Neurobiology of Motivation and Adaptive Decision-Making

Research Description

My laboratory investigates how mammalian neural circuits achieve critical psychological functions including decision-making and learning. We have a particular focus on the basal ganglia - their dynamics in normal awake, behaving animals and in pathological conditions such as drug addiction, Parkinson’s disease, Huntington’s Disease and Tourette Syndrome. We combine sophisticated behavioral tasks with a range of state-of-the-art techniques including electrophysiological recording of many individual neurons, real-time neurochemical measures, and optogenetic manipulations. We are also actively involved in developing new technologies for systems neuroscience.

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Current Projects

Neuromodulators and behavioral control. Dopamine seems to be critical for reinforcement-driven learning, and also seems to be critical for motivation to work for rewards. We have been studying how, and why, dopamine plays this dual role through a series of neurochemical and optogenetic experiments (e.g. Hamid et al. 2015). We are also studying how dopamine and acetylcholine signaling interact to sculpt motivational value and behavioral plasticity.

Behavioral inhibition. One major function of reinforcement learning is to allow us to rapidly and effortlessly perform actions that have reliably lead to reward. However, we often need to modify behavior as circumstances change, and specific mechanisms within the basal ganglia appear to faciliate behavioral flexibility by slowing or stopping the initiation of well-trained actions. In a series of ongoing studies we have been investigating how particular microcircuits and macrocircuits contribute to this suppression of actions (e.g. Schmidt et al. 2013, Mallet et al. 2016).

Investigating microcircuitry using ultra-high-density electrophysiology and electrochemistry. Existing electrodes for in vivo recording sample only a small fraction of neurons within a microcircuit, in part because they are too large to be placed at high density without destroying the circuit. In our current BRAIN Initiative grant (with Cindy Chestek, Michigan) we have been developing dense arrays of very thin carbon fibers that provide a far more complete picture of microcircuit dynamics, including both single-unit firing and rapid neurochemical modulation.

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Lab Members

Post-doctoral fellows (as of June 2016)

Michael Farries
Bon-Mi Gu
Ali Mohebi
Jeff Pettibone

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Selected Publications

Arkypallidal Cells Send a Stop Signal to Striatum.
Mallet N, Schmidt R, Leventhal D, Chen F, Amer N, Boraud T, Berke JD.
Neuron. 2016 Jan 12.

Hamid A, Pettibone JR, Mabrouk OS, Hetrick V, Schmidt R, VanderWeele C, Kennedy RT, Aragona BJ, Berke JD (2015). Mesolimbic dopamine signals the value of work. Nature Neuroscience, doi: 10.1038/nn.4173.

Schmidt R, Leventhal DK, Mallet N, Chen F, Berke JD (2013). Canceling actions involves a race between basal ganglia pathways. Nature Neuroscience 16:1118-24.

Leventhal DK, Gage GJ, Schmidt R, Pettibone JR, Case AC, Berke JD (2012). Basal ganglia beta oscillations accompany cue utilization. Neuron, 73: 523-536.

Gage GJ, Stoetzner CR, Wiltschko AB, Berke JD (2010). Selective activation of striatal fast spiking interneurons during choice execution.  Neuron, 67: 466-479.

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Joshua Berke, Ph.D.


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