VIP+ interneurons control neocortical activity across brain states

J Neurophysiol. 2016 Jun 1;115(6):3008-17. doi: 10.1152/jn.01124.2015. Epub 2016 Mar 9.

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.

Keywords: GABA; interneurons; neocortex; network; spontaneous activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology
  • Female
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Locomotion / physiology
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Neocortex / physiology*
  • Nerve Net / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / genetics
  • Neural Inhibition / physiology*
  • Photic Stimulation
  • Receptor, Muscarinic M4 / genetics
  • Receptor, Muscarinic M4 / metabolism
  • Somatostatin / genetics
  • Somatostatin / metabolism
  • Transduction, Genetic
  • Vasoactive Intestinal Peptide / genetics
  • Vasoactive Intestinal Peptide / metabolism*
  • Visual Cortex / cytology*
  • gamma-Aminobutyric Acid

Substances

  • Luminescent Proteins
  • Receptor, Muscarinic M4
  • Vasoactive Intestinal Peptide
  • Somatostatin
  • gamma-Aminobutyric Acid
  • Clozapine
  • clozapine N-oxide
  • Calcium