Functional coupling between mGluR1 and Cav3.1 T-type calcium channels contributes to parallel fiber-induced fast calcium signaling within Purkinje cell dendritic spines.
T-type voltage-gated calcium channels are expressed in the dendrites of many neurons, although their functional interactions with postsynaptic receptors and contributions to synaptic signaling are not well understood. We combine electrophysiological and ultrafast two-photon calcium imaging to demonstrate that mGluR1 activation potentiates cerebellar Purkinje cell Ca(v)3.1 T-type currents via a G-protein- and tyrosine-phosphatase-dependent pathway. Immunohistochemical and electron microscopic investigations on wild-type and Ca(v)3.1 gene knock-out animals show that Ca(v)3.1 T-type channels are preferentially expressed in Purkinje cell dendritic spines and colocalize with mGluR1s. We further demonstrate that parallel fiber stimulation induces fast subthreshold calcium signaling in dendritic spines and that the synaptic Ca(v)3.1-mediated calcium transients are potentiated by mGluR1 selectively during bursts of excitatory parallel fiber inputs. Our data identify a new fast calcium signaling pathway in Purkinje cell dendritic spines triggered by short burst of parallel fiber inputs and mediated by T-type calcium channels and mGluR1s.
Hildebrand
Michael E
ME
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Isope
Philippe
P
Miyazaki
Taisuke
T
Nakaya
Toshitaka
T
Garcia
Esperanza
E
Feltz
Anne
A
Schneider
Toni
T
Hescheler
Jürgen
J
Kano
Masanobu
M
Sakimura
Kenji
K
Watanabe
Masahiko
M
Dieudonné
Stéphane
S
Snutch
Terrance P
TP
D000375:Aging; D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011689:Purkinje Cells / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
C498197:Cacna1g protein, mouse; C500994:Cacna1g protein, rat; D020747:Calcium Channels, T-Type; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1