cortical plasticity, neural stem cells, inhibitory interneurons, vision
2012 Klingenstein Fellow
2013 Searle Scholar
2013 NIH Director's New Innovator Award
2017 Kavli Fellow
University of California, San Francisco
The brain has the remarkable capacity to rewire its connections and thereby reorganize its function. In the juvenile brain, the plasticity of neuronal connections mediates the fine-tuning of a wide range of behaviors, from visual perception to language acquisition to social recognition. What mechanism regulates the plasticity of connections in the young brain? How might we manipulate neural circuits to reactivate this plasticity?
In the visual cortex, modifications of GABAergic inhibition have been shown to elicit the plasticity of neuronal connections and responses, but the mechanism by which inhibition regulates such plasticity remains poorly understood. We recently gained insight into this process when we discovered that the transplantation of GABAergic interneurons into the visual cortex induces a new period of plasticity after the normal juvenile period had terminated. Our finding strongly suggests that interneurons are developmentally programmed to regulate cortical plasticity.
Current projects in the lab are focused on understanding how interneurons control cortical plasticity. We employ a combination of techniques including two-photon functional imaging, in vivo patch-clamp recordings, the transplantation of neuronal precursors, and mouse genetic tools that identify, stimulate and silence defined neural circuits.
Understanding how interneurons regulate plasticity may eventually spur new cell-based therapies for brain repair. Beyond plasticity, these studies may also shed light on the disorders such as autism and schizophrenia that have been proposed to arise from neurodevelopmental imbalances in neocortical excitation and inhibition.
Salinas, K.J., Figueroa Velez, D.X., Zeitoun, J.H., Kim, H., Gandhi, S.P. (2017) Contralateral bias of high spatial frequency tuning and cardinal directional selectivity in mouse visual cortex. Journal of Neuroscience. PMID: 28924011
Figueroa Velez, D.X., Ellefsen, K.E., Hathaway, E.R., Carathedathu, M.C., Gandhi, S.P. (2017) Contribution of innate cortical mechanisms to the maturation of orientation selectivity in Parvalbumin interneurons. Journal of Neuroscience. 37(4):820-829 PMID: 28123018
Sun .Y, Ikrar T., Davis M.F., Gong N., Zheng X., Luo Z.D., Lai C., Mei L., Holmes T.C., Gandhi S.P., Xu X. (2016) Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity. Neuron. Sep 9. pii: S0896-6273(16)30526-8. doi: 10.1016/j.neuron.2016.08.033.
Davis, M. F., Figueroa Velez, D.X., Guevarra, R.P., Yang, M.C., Habeeb, M., Carathedathu, M.C., Gandhi, S.P. (2015) Inhibitory neuron transplantation into adult visual cortex creates a new critical period that rescues impaired vision. Neuron. 2015 May 20;86(4):1055-66. doi: 10.1016/j.neuron.2015.03.062.
Southwell, D.G., Alvarez-Buylla, A., Stryker, M.P., Gandhi, S.P. (2010) Cortical plasticity induced by inhibitory neuron transplantation. Science. 327(596): 1145-1148. doi:10.1126/science.1183962.
Gandhi, S.P., Yanagawa, Y., Stryker, M.P. (2008) Delayed plasticity of inhibitory neurons in developing visual cortex. Proc. Nat. Acad. Sci. USA 105: 16797-16802. doi: 10.1073/pnas.0806159105
Gandhi, S.P., Cang, J., Stryker, M.P. (2005) An eye-opening experience. Nat. Neurosci. 8(1):9- 10. doi:10.1038/nn0105-9
Gandhi, S.P., Stevens, C.F. (2003) Three modes of synaptic vesicular recycling revealed by single vesicle imaging. Nature. 423: 607-13
Heeger, D.J., Gandhi, S.P., Huk, A.C., & Boynton, G.M. (2001) Neuronal correlates of attention in human visual cortex. In J. Braun, C. Koch, & J. Davis (Eds.), Visual Attention and Cortical Circuits (pp. 25-47). Cambridge, MA: MIT Press.
Gandhi, S.P. (2001) Memory retrieval: reactivating sensory cortex. Curr. Biol. 11(1):R32-34
Wandell, B.A., Poirson, A.A., Baseler, H.A., Boynton, G.M., Huk, A.C., Gandhi, S.P., & Sharpe, L.T. (1999) Color signals in human motion-selective cortex. Neuron. 24, 901-909
Gandhi, S.P., Heeger, D.J., Boynton G.M. (1999) Spatial attention affects brain activity in human primary visual cortex. Proc. Natl. Acad. Sci. 96:3314-3319
Neurobiology and Behavior
Interdepartmental Neuroscience Program
Center for Hearing Research
Center for the Neurobiology of Learning and Memory