Cerebral Cortex Advance Access originally published online on June 10, 2004
Cerebral Cortex 2004 14(12):1310-1327; doi:10.1093/cercor/bhh092
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© Oxford University Press 2004
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Correlation Maps Allow Neuronal Electrical Properties to be Predicted from Single-cell Gene Expression Profiles in Rat Neocortex
1 Brain and Mind Institute, EPFL, Lausanne 1015, Switzerland, 2 Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel, 3 Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA, 4 Department of Physiology, Medical School, Tel Aviv University, Tel Aviv 69978, Israel, 5 Department of Internal Medicine, University of Nevada, Reno, NV 89557, USA
The computational power of the neocortex arises from interactions of multiple neurons, which display a wide range of electrical properties. The gene expression profiles underlying this phenotypic diversity are unknown. To explore this relationship, we combined whole-cell electrical recordings with single-cell multiplex RT-PCR of rat (p13–16) neocortical neurons to obtain cDNA libraries of 26 ion channels (including voltage activated potassium channels, Kv1.1/2/4/6, Kvß1/2, Kv2.1/2, Kv3.1/2/3/4, Kv4.2/3; sodium/potassium permeable hyperpolarization activated channels, HCN1/2/3/4; the calcium activated potassium channel, SK2; voltage activated calcium channels, Ca
1A/B/G/I, Caß1/3/4), three calcium binding proteins (calbindin, parvalbumin and calretinin) and GAPDH. We found a previously unreported clustering of ion channel genes around the three calcium-binding proteins. We further determined that cells similar in their expression patterns were also similar in their electrical properties. Subsequent regression modeling with statistical resampling yielded a set of coefficients that reliably predicted electrical properties from the expression profile of individual neurons. This is the first report of a consistent relationship between the co-expression of a large profile of ion channel and calcium binding protein genes and the electrical phenotype of individual neocortical neurons.
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