VIP+ interneurons control neocortical activity across brain states

• DOI: 10.1152/jn.01124.2015
• Publication Date: 2016-03-10T04:24:41Z
• Authors: Jesse Jackson; Inbal Ayzenshtat; Mahesh M. Karnani; Rafael Yuste
• Keywords: Male; 0303 health sciences; Receptor, Muscarinic M4; Mice, Transgenic; Neocortex; Neural Inhibition; Luminescent Proteins; Mice; 03 medical and health sciences; Interneurons; Transduction, Genetic; Animals; Calcium; Female; Nerve Net; Somatostatin; Clozapine; Locomotion; Photic Stimulation; gamma-Aminobutyric Acid; Vasoactive Intestinal Peptide; Visual Cortex

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 Ca2+ 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.