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Cerebral Cortex Advance Access published online on June 10, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh092
© 2004 by Oxford University Press
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Article

Correlation Maps Allow Neuronal Electrical Properties to be Predicted from Single-cell Gene Expression Profiles in Rat Neocortex

Maria Toledo-Rodriguez 1, Barak Blumenfeld 2, Caizhi Wu 3, Junyi Luo 3, Bernard Attali 4, Philip Goodman 5, Henry Markram 6*

1 Brain and Mind Institute, EPFL, Lausanne 1015, Switzerland; Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
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
6 Brain and Mind Institute, EPFL, Lausanne 1015, Switzerland

* To whom correspondence should be addressed. E-mail: henry.markram{at}epfl.ch.


  Abstract

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 wholecell 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, Kv{beta}1/2, 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{alpha}1A/B/G/I, Ca{beta}1/3/4), three calcium binding proteins (calbindin, parvalbumin and calretinin) and GAPDH. We found a previously unreported clustering of ion channel genes around the three calciumbinding 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.

Key Words: cortex, electrophysiology, ion channel, neuron, single-cell RT-PCR


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