title: 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.
authors.affiliation: Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Cohen
authors.affiliation: Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA; Department of Physiology, Institute of Neuroscience, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA; Molecular Neurobiology Program, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine and Departments of Otolaryngology, Neuroscience and Physiology, Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Kishore V
authors.initials: KV
authors.lastname: Kuchibhotla
authors.affiliation: Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA; Department of Psychiatry and Mind Brain Research Institute, Weill-Cornell Medical College, New York, NY 10021, USA.
authors.forename: Brendon O
authors.initials: BO
authors.lastname: Watson
authors.affiliation: Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA; Center for Neural Science, New York University, New York, NY 10003, USA.
authors.forename: György
authors.initials: G
authors.lastname: Buzsáki
authors.affiliation: Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA; Center for Neural Science, New York University, New York, NY 10003, USA; Molecular Neurobiology Program, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine and Departments of Otolaryngology, Neuroscience and Physiology, Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Froemke
authors.affiliation: Department of Neuroscience and Physiology and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY 10016, USA; Center for Neural Science, New York University, New York, NY 10003, USA. Electronic address: richard.tsien@nyumc.org.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsien
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D051242:Caveolin 1 / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism* / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D010320:Parvalbumins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium