当前位置： SCI文献检索 > NEURON期刊下所有文献 > Excitation-Transcription Coupling in Parvalbumin-Positive Interneurons Employs a Novel CaM Kinase-Dependent Pathway Distinct from Excitatory Neurons.

Excitation-Transcription Coupling in Parvalbumin-Positive Interneurons Employs a Novel CaM Kinase-Dependent Pathway Distinct from Excitatory Neurons.

Abstract：

:Properly functional CNS circuits depend on inhibitory interneurons that in turn rely upon activity-dependent gene expression for morphological development, connectivity, and excitatory-inhibitory coordination. Despite its importance, excitation-transcription coupling in inhibitory interneurons is poorly understood. We report that PV+ interneurons employ a novel CaMK-dependent pathway to trigger CREB phosphorylation and gene expression. As in excitatory neurons, voltage-gated Ca(2+) influx through CaV1 channels triggers CaM nuclear translocation via local Ca(2+) signaling. However, PV+ interneurons are distinct in that nuclear signaling is mediated by γCaMKI, not γCaMKII. CREB phosphorylation also proceeds with slow, sigmoid kinetics, rate-limited by paucity of CaMKIV, protecting against saturation of phospho-CREB in the face of higher firing rates and bigger Ca(2+) transients. Our findings support the generality of CaM shuttling to drive nuclear CaMK activity, and they are relevant to disease pathophysiology, insofar as dysfunction of PV+ interneurons and molecules underpinning their excitation-transcription coupling both relate to neuropsychiatric disease.

journal_name

Neuron

journal_title

Neuron

authors

Cohen SM,Ma H,Kuchibhotla KV,Watson BO,Buzsáki G,Froemke RC,Tsien RW

doi

10.1016/j.neuron.2016.03.001

subject

Has Abstract

pub_date

2016-04-20 00:00:00

pages

292-307

issue

2

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(16)00180-X

journal_volume

90

pub_type

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