Suchergebnisse

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. ; Paper published in eLife: https://elifesciences.org/content/6/e26177 This work was supported by the ERC (NEURO-PATTERNS), NIH (1U01NS090576-01), FP7 (DESIRE), MIUR FIRB (RBAP11X42L) to TF, and, in part, from Flag-Era JTC Human Brain Project (SLOW-DYN) to TF and SP. M.M-M has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 699829.

Orexins (also called hypocretins) are hypothalamic neuropeptides that carry out essential functions in the central nervous system; however, little is known about their release and range of action in vivo owing to the limited resolution of current detection technologies. Here we developed a genetically encoded orexin sensor (OxLight1) based on the engineering of circularly permutated green fluorescent protein into the human type-2 orexin receptor. In mice OxLight1 detects optogenetically evoked release of endogenous orexins in vivo with high sensitivity. Photometry recordings of OxLight1 in mice show rapid orexin release associated with spontaneous running behavior, acute stress and sleep-to-wake transitions in different brain areas. Moreover, two-photon imaging of OxLight1 reveals orexin release in layer 2/3 of the mouse somatosensory cortex during emergence from anesthesia. Thus, OxLight1 enables sensitive and direct optical detection of orexin neuropeptides with high spatiotemporal resolution in living animals. ; The results are part of a project that has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 891959; to T.P.). We also acknowledge funding from the University of Zurich and the Swiss National Science Foundation (grant no. 310030_196455; to T.P.); Forschungskredit Candoc (to X.Z.); ETH Zurich (to D.B.); Swiss National Science Foundation (grant no. PCEFP3_181282; to M.S.); ERC-2017-STG (grant agreement no. 758448; to N.G.); Swiss National Science Foundation and ERC-2016-CoG (grant agreement no. 725850) (A.R.A.); University of Bern and Inselspital University Hospital (A.R.A. and M.H.S.); ERC-2014-CoG (grant agreement no. 647725) and National Institutes of Health Brain Initiative (U19 NS107464) (both to T.F.); H2020-ICT (grant agreement no. 101016787; to T.P. and T.F.). We thank J.-C. Paterna and the VVF of the Neuroscience Center Zurich for help with virus production, M. Drobizhev (Montana State ...