Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex.
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, Kvbeta1/2, 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, Caalpha1A/B/G/I, Cabeta1/3/4), 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.
Toledo-Rodriguez
Maria
M
Brain and Mind Institute, EPFL, Lausanne 1015, Switzerland.
Blumenfeld
Barak
B
Wu
Caizhi
C
Luo
Junyi
J
Attali
Bernard
B
Goodman
Philip
P
Markram
Henry
H
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020869:Gene Expression Profiling / Q000379:methods*; D066298:In Vitro Techniques; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011237:Predictive Value of Tests; D051381:Rats; D017208:Rats, Wistar