Gordon Fishell, PhD
Professor and Coordinator of the Smilow
Ph.D., 1989 University of Toronto
Neural progenitor, Genetics, Forebrain, Epilepsy, Autism Spectral Disease, Cortical Interneurons
The Fishell laboratory uses mice to study cortical microcircuits. In particular we are interested in cortical interneurons, which are generated within the medial and caudal ganglionic eminences. We wish to understand the logic of the combinatorial codes by which different classes of cortical interneurons are generated and wish to relate this code to their emergent properties including: their synaptic connectivity, intrinsic firing properties and their unique morphologies.
Understanding the embryonic molecular and genetic origins of cortical interneurons promises to open the way for understanding how different functional classes of interneurons are generated and the logic by which each subclass contribute to the assembly of cortical microcircuits. Our goals in this regard are three fold and together they comprise the breadth of interests of the Fishell laboratory.
1. Using inducible genetic fate mapping and conditional loss of function analysis, in combination with genome-wide microarray analysis of cortical interneurons to study how developmental gene expression leads to the emergence of cortical interneurons with distinct functional properties.
2. To use the precision achieved through genetic methods to understand the “rules” by which specific subclasses of cortical interneurons integrate into the postnatal cortex.
3. Beyond understanding the logic by which cortical microcircuits develop, we wish to develop genetic tools by which specific cortical interneuronal populations can be manipulated to a) trace their synaptic circuitry b) visualize, induce or suppress their activity in vivo c) explore the cellular mechanisms by which they maintain their unique architectures.
Through these multifaceted methods, a picture of the logic by which cortical microcircuits are established is beginning to emerge. At present we are examining how the loss of developmental genes affects the gene expression patterns, electrophysiological properties and fine cytoarchitecture of the mature neurons. Through this effort we are beginning to connect embryonic gene expression to mature neuronal phenotypes.
Research is supported by the NINDS, NIMH, NYSTEM, The Simons Foundation.
- De Marco-Garcia, N.V., Karayannis, T., and Fishell, G. (2011) Neuronal activity is required for the development of specific cortical interneuron subtypes. Nature, 472, 351-355. PMID: 21460837
- Miyoshi, G., Hjerling-Leffler, J., Karayannis, T., Sousa, V.H., Butt, S.J.B., Battiste, J., Johnson, J.E., Machold, R.P. and Fishell, G. (2010) Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. Journal of Neuroscience, 30: 1582-1594. PMID: 20130169
- Batista-Brito, R., Rossignol,E., Hjerling-Leffler, J., Denaxa, M., Wegner, M., Lefebvre, V., Pachnis, V. and Fishell, G. (2009) The cell-intrinsic requirement of Sox6 for cortical interneuron development. Neuron, 63: 466-481. PMID: 19709629
- Butt, S., J., Sousa, V.H., Fuccillo, M., Hjerling-Leffler, J., Miyoshi, G., Kimura, S. and Fishell, G. (2008) The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes. Neuron, 59: 722-732. PMID: 18786356