RT Journal Article
SR Electronic
T1 Activity patterns in the neuropil of striatal cholinergic interneurons in freely moving mice represent their collective spiking dynamics
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0351-18.2018
DO 10.1523/ENEURO.0351-18.2018
A1 Rotem Rehani
A1 Yara Atamna
A1 Lior Tiroshi
A1 Wei-Hua Chiu
A1 José de Jesús  Aceves Buendía
A1 Gabriela J. Martins
A1 Gilad A. Jacobson
A1 Joshua A. Goldberg
YR 2019
UL http://www.eneuro.org/content/early/2019/01/04/ENEURO.0351-18.2018.abstract
AB Cholinergic interneurons (CINs) are believed to form synchronous cell assemblies that modulate the striatal microcircuitry and possibly orchestrate local dopamine release. We expressed GCaMP6s, a genetically encoded calcium indicator (GECIs), selectively in CINs, and used microendoscopes to visualize the putative CIN assemblies in the dorsal striatum of freely moving mice. The GECI fluorescence signal from the dorsal striatum was composed of signals from individual CIN somata that were engulfed by a widespread fluorescent neuropil. Bouts of synchronous activation of the cholinergic neuropil revealed patterns of activity that preceded the signal from individual somata. To investigate the nature of the neuropil signal and why it precedes the somatic signal, we target-patched GECI-expressing CINs in acute striatal slices in conjunction with multiphoton imaging or wide-field imaging that emulates the microendoscopes’ specifications. The ability to detect fluorescent transients associated with individual action potential was constrained by the long decay constant of GECIs (relative to common inorganic dyes) to slowly firing (< 2 spikes/s) CINs. The microendoscopes’ resolving power and sampling rate further diminished this ability. Additionally, we found that only back-propagating action potentials but not synchronous optogenetic activation of thalamic inputs elicited observable calcium transients in CIN dendrites. Our data suggest that only bursts of CIN activity (but not their tonic firing) are visible using endoscopic imaging, and that the neuropil patterns are a physiological measure of the collective recurrent CIN network spiking activity.Significance Statement Cholinergic interneurons (CINs) are key modulators of the striatal microcircuitry that are necessary for assigning action value and behavioral flexibility. We present a first endoscopic imaging study of multiple molecularly identified CINs in freely moving mice. We reveal the presence of activity patterns in the CIN neuropil. We then use ex vivo electrophysiological and imaging techniques to show that the neuropil signal is the integrated fluorescence arising from the axo-dendritic arbors of CINs dispersed throughout the striatum. We conclude that the neuropil signal acts as a mean-field readout of the striatal CIN network activity.