title: Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs.
abstract: The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response.
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: Spiegel
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Mardinly
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Harrison W
authors.initials: HW
authors.lastname: Gabel
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Bazinet
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Cameron H
authors.initials: CH
authors.lastname: Couch
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Tzeng
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Harmin
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: meg@hms.harvard.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D004622:Embryo, Mammalian / Q000166:cytology; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C533005:Npas4 protein, mouse