Neuroscience Graduate Program at UCSF
Information Processing in Cortical Microcircuits: Optogenetic Tools and Implications for Psychiatric Disease
The overall goal of our laboratory is to understand how the interactions of cells and synapses in the cortex generate patterns of activity that carry out specific functions, and how this process is altered in psychiatric disorders. We have focused on the prefrontal cortex because of its important role in disorders such as schizophrenia and autism. Currently, our research is organized around two major themes. First, how does dopamine modulate specific subtypes of prefrontal neurons, and thereby alter prefrontal function? Second, how do inhibitory interneurons control patterns of prefrontal circuit activity, including gamma oscillations, and how do gamma oscillations and related phenomena contribute to normal circuit function? We are addressing these questions using a combination of techniques that include whole cell patch clamp, dynamic clamp, information theoretic analysis, brain slice electrophysiology, Ca2+ imaging, computational modeling, optogenetic stimulation in vitro and in vivo, EEG recording, and rodent behavioral assays.
- How does dopamine modulate specific subtypes of prefrontal neurons, network activity in the prefrontal cortex, and prefrontal cortex-dependent behaviors in mice? How do these effects relate to psychiatric disorders such as schizophrenia?
- How do recurrent networks in the neocortex transform their inputs into patterns of output activity? What cellular and synaptic mechanisms influence the emergent patterns of output generated by these networks?
- What are the cellular and neural circuit mechanisms by which psychotomimetics produce their pathological effects on prefrontal cortical function?
- How do specific properties of parvalbumin interneurons influence emergent gamma oscillations in cortical microcircuits? How does parvalbumin interneuron dysfunction contribute to disorders such as schizophrenia and autism?
- How do gamma oscillations contribute to information processing in single neurons and cognition in behaving mice?
B.S., CSU-Los Angeles
M.D. / Ph.D., U. of Colorado
B.S., Stanford University
B.A., Skidmore College
- Sohal VS and Huguenard JR (2005). Inhibitory coupling specifically generates emergent gamma oscillations in diverse cell types. Proceedings of the National Academy of Sciences USA 102: 18638-43.
- Sohal VS*, Zhang F*, Yizhar O, and Deisseroth KD (2009). Parvalbumin neurons and gamma rhythms enhance cortical microcircuit performance. Nature 459: 698-702.
- Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K (2011). Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477: 171-8.
- Sohal VS (2012). Insights into cortical oscillations arising from optogenetic studies. Biological Psychiatry, Available online ahead of print.
- Gee S, Ellwood I, Patel T, Luongo F, Deisseroth K, and Sohal VS (2012). Synaptic activity unmasks dopamine D2 receptor modulation of a specific class of layer V pyramidal neurons in prefrontal cortex. Journal of Neuroscience 32: 4959-71.