Biology subjects

Atamna, Y.

Publications and source records attributed to Atamna, Y..

3 recordsLinked to original sources

bioRxiv2022

Striatal neurons are recruited dynamically into collective representations of self-initiated and learned actions in freely-moving mice

Striatal spiny projection neurons are hyperpolarized-at-rest (HaR) and are driven to spike threshold by a small number of powerful inputs - an input-output configuration that is detrimental to response reliability. Because the striatum is important for habitual behaviors and goal-directed learning, we conducted microendoscopic imaging in freely-moving mice that express a genetically-encoded calcium indicator sparsely in striatal HaR neurons to compare their response reliability during self-initiated movements and operant conditioning. The sparse expression was critical for longitudinal studies of response reliability, and for studying correlations among HaR neurons while minimizing spurious correlations arising from contamination by the background neuropil signal. We found that HaR neurons are recruited dynamically into action representation through a moment-by-moment formation of distinct cell assemblies. While individual neurons respond with little reliability, the population response remained reliable. Moreover, we found evidence for the formation of correlated cell assemblies during conditioned (but not innate) behaviors, but this correlation was independent of the distance between neurons.

neuroscience↗

bioRxiv2022

Mechanism of dopamine traveling waves in the striatum: theory and experiment

Striatal dopamine (DA) encodes reward, with recent work showing that DA release occurs in spatiotemporal waves. However, the mechanism of DA waves is unknown. Here we report that the striatal cholinergic neuropil also exhibits wave-like activity, and that the spatial scale of striatal DA release is extended by nicotinic receptors. Based on these findings we hypothesized that the local reciprocal interaction between cholinergic interneurons (CIN) and DA axons suffices to drive endogenous traveling waves. We show that the morphological and physiological properties of the CIN-DA interaction can be modeled as a reaction-diffusion system that gives rise to traveling waves. Analytically-tractable versions of the model show that the structure and the nature of propagation of CIN and DA traveling waves depend on their coupling, and that traveling waves can give rise to empirically observed correlations between these signals. Our model provides a biophysical mechanism for wave formation and predicts that the observed DA and CIN waves are strongly coupled phenomena.

neuroscience↗

bioRxiv2018

Wave-like activity patterns in the neuropil of striatal cholinergic interneurons in freely moving mice represent their collective spiking dynamics

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 traveling-wave-like 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 spatiotemporal neuropil patterns are a physiological measure of the collective recurrent CIN network spiking activity.\n\nSignificance StatementCholinergic 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 traveling-wave-like activity 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.

neuroscience↗