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

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 po...

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Veröffentlicht in:Neuron (Cambridge, Mass.) Mass.), 2016-04, Vol.90 (2), p.292-307
Hauptverfasser: Cohen, Samuel M., Ma, Huan, Kuchibhotla, Kishore V., Watson, Brendon O., Buzsáki, György, Froemke, Robert C., Tsien, Richard W.
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container_end_page 307
container_issue 2
container_start_page 292
container_title Neuron (Cambridge, Mass.)
container_volume 90
creator Cohen, Samuel M.
Ma, Huan
Kuchibhotla, Kishore V.
Watson, Brendon O.
Buzsáki, György
Froemke, Robert C.
Tsien, Richard W.
description 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 Ca2+ influx through CaV1 channels triggers CaM nuclear translocation via local Ca2+ 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 Ca2+ 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. •Voltage-gated Ca2+ influx triggers nuclear translocation of CaM in PV+ interneurons•CaMK signaling promotes CREB phosphorylation and activates key genes in PV+ cells•γCaMKI, not γCaMKII, operates to shuttle CaM to the nucleus in PV+ cells•Low CaMKIV levels rate-limit CREB phosphorylation in PV+ cells Activity-dependent gene regulation is critical for long-term plasticity. Cohen et al. demonstrate that PV+ cortical interneurons rely on a CaM kinase-dependent signaling pathway, hinging on γCaMKI and rate-limited by CaMKIV, to trigger CREB phosphorylation and gene expression.
doi_str_mv 10.1016/j.neuron.2016.03.001
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We report that PV+ interneurons employ a novel CaMK-dependent pathway to trigger CREB phosphorylation and gene expression. As in excitatory neurons, voltage-gated Ca2+ influx through CaV1 channels triggers CaM nuclear translocation via local Ca2+ 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 Ca2+ transients. 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We report that PV+ interneurons employ a novel CaMK-dependent pathway to trigger CREB phosphorylation and gene expression. As in excitatory neurons, voltage-gated Ca2+ influx through CaV1 channels triggers CaM nuclear translocation via local Ca2+ 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 Ca2+ transients. 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subjects Acoustic Stimulation
Animals
Auditory Cortex - metabolism
Calcium - metabolism
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Caveolin 1 - physiology
Cyclic AMP Response Element-Binding Protein - metabolism
Experiments
Gene expression
Immunoglobulins
Interneurons - metabolism
Interneurons - physiology
Isoenzymes - metabolism
Kinases
Mice
Neurons
Neurons - metabolism
Neurons - physiology
Parvalbumins - metabolism
Phosphorylation
Rats
Signal Transduction
Statistical analysis
Transcription, Genetic - physiology
title Excitation-Transcription Coupling in Parvalbumin-Positive Interneurons Employs a Novel CaM Kinase-Dependent Pathway Distinct from Excitatory Neurons
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