An inhibitory gate for state transition in cortex

Abstract

Large scale transitions between active (up) and silent (down) states during quiet wakefulness or NREM sleep regulate fundamental cortical functions and are known to involve both excitatory and inhibitory cells. However, if and how inhibition regulates these activity transitions is unclear. Using fluorescence-targeted electrophysiological recording and cell-specific optogenetic manipulation in both anesthetized and non-anesthetized mice, we found that two major classes of interneurons, the parvalbumin and the somatostatin positive cells, tightly control both up-to-down and down-to-up state transitions. Inhibitory regulation of state transition was observed under both natural and optogenetically-evoked conditions. Moreover, perturbative optogenetic experiments revealed that the inhibitory control of state transition was interneuron-type specific. Finally, local manipulation of small ensembles of interneurons affected cortical populations millimetres away from the modulated region. Together, these results demonstrate that inhibition potently gates transitions between cortical activity states, and reveal the cellular mechanisms by which local inhibitory microcircuits regulate state transitions at the mesoscale.DOI: http://dx.doi.org/10.7554/eLife.26177.001

Local sleep-like cortical reactivity in the awake brain after focal injury

“…The hallmark of physiological sleep is the occurrence of slow waves and OFF-periods, often referred to in the sleep literature as cortical bistability (7,10). OFF-periods are caused by the enhancement of adaptation (or activity-dependent) K+ currents, brought about by decreased levels of neuromodulation from brainstem activating systems (36)(37)(38)(39) and/or by increased inhibition (40)(41)(42). Due to these mechanisms, cortical neurons tend to plunge into a silent, hyperpolarized state, lasting few hundred milliseconds, after an initial activation (10).…”

Brain states govern the spatio-temporal dynamics of resting state functional connectivity

“…In persistent state, which can occur during but is not limited to awake periods, neurons are rather depolarized, sparsely active, leading to temporally dynamic, modality specific, network configurations 18 . In contrast to the persistent state, stands the bimodal activity pattern of slow oscillations, or slow wave state which has been extensively described 5,11,[19][20][21][22][23][24][25] , but only most recently in the framework of BOLD fMRI 11,26,27 . The corresponding low-frequency component ranges at 0.2-1 Hz, reflecting alternating activity patterns: active ("up") periods in which cells are depolarized and fire action potentials in temporally restricted periods, and silence ("down") periods with rather hyperpolarized membrane potentials and an almost complete absence of neuronal activity 28,29 .…”

Control of brain state transitions with light

“…53 Optogenetics 54,55 has emerged as an alternative to controlling brain waves with electromagnetic fields: photocontrolling the release of ACh, which strongly modulates the transitions between different brain states, 9,12 is possible by overexpressing photosensitive proteins in cholinergic neurons of mice neocortex. 10,56,57 However, genetic manipulation is required in this approach, and our light-dependent cholinergic muscarinic ligand is so far the only way to directly photomodulate cholinergic pathways in intact tissue. We first studied the effect of the superagonist Iperoxo 37 on isolated cortical slices ( Fig.…”

“…65 Compared to the local and often inhomogeneous expression patterns achieved with viral injections of optogenetic constructs, diffusible small molecules like PAI can be in principle applied to larger brain regions to control neuronal oscillations. 57 Thus, remote control of brain waves based on the photopharmacological manipulation of endogenous muscarinic receptors may reveal the complex 3D molecular signalling underlying brain states and their transitions, in order to link them with cognition and behavior in a diversity of wildtype organisms.…”