title: VIP+ interneurons control neocortical activity across brain states.
abstract: GABAergic interneurons are positioned to powerfully influence the dynamics of neural activity, yet the interneuron-mediated circuit mechanisms that control spontaneous and evoked neocortical activity remains elusive. Vasoactive intestinal peptide (VIP+) interneurons are a specialized cell class which synapse specifically on other interneurons, potentially serving to facilitate increases in cortical activity. In this study, using in vivo Ca(2+) imaging, we describe the interaction between local network activity and VIP+ cells and determine their role in modulating neocortical activity in mouse visual cortex. VIP+ cells were active across brain states including locomotion, nonlocomotion, visual stimulation, and under anesthesia. VIP+ activity correlated most clearly with the mean level of population activity of nearby excitatory neurons during all brain states, suggesting VIP+ cells enable high-excitability states in the cortex. The pharmacogenetic blockade of VIP+ cell output reduced network activity during locomotion, nonlocomotion, anesthesia, and visual stimulation, suggesting VIP+ cells exert a state-independent facilitation of neural activity in the cortex. Collectively, our findings demonstrate that VIP+ neurons have a causal role in the generation of high-activity regimes during spontaneous and stimulus evoked neocortical activity.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York jacksonj10@janelia.hhmi.org.
authors.forename: Jesse
authors.initials: J
authors.lastname: Jackson
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York.
authors.forename: Inbal
authors.initials: I
authors.lastname: Ayzenshtat
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York.
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Karnani
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York.
authors.forename: Rafael
authors.initials: R
authors.lastname: Yuste
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008124:Locomotion / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D010775:Photic Stimulation; D043588:Receptor, Muscarinic M4 / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*; D014793:Visual Cortex / Q000166:cytology*; D005680:gamma-Aminobutyric Acid
chemical_list: D008164:Luminescent Proteins; D043588:Receptor, Muscarinic M4; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D003024:Clozapine; C079149:clozapine N-oxide; D002118:Calcium
keywords: GABA; interneurons; neocortex; network; spontaneous activity