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Publication : Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons.

First Author  Oz O Year  2022
Journal  Elife Volume  11
PubMed ID  35815934 Mgi Jnum  J:351506
Mgi Id  MGI:7316117 Doi  10.7554/eLife.76039
Citation  Oz O, et al. (2022) Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons. Elife 11:e76039
abstractText  The tonic activity of striatal cholinergic interneurons (CINs) is modified differentially by their afferent inputs. Although their unitary synaptic currents are identical, in most CINs cortical inputs onto distal dendrites only weakly entrain them, whereas proximal thalamic inputs trigger abrupt pauses in discharge in response to salient external stimuli. To test whether the dendritic expression of the active conductances that drive autonomous discharge contribute to the CINs' capacity to dissociate cortical from thalamic inputs, we used an optogenetics-based method to quantify dendritic excitability in mouse CINs. We found that the persistent sodium (NaP) current gave rise to dendritic boosting, and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) current gave rise to a subhertz membrane resonance. This resonance may underlie our novel finding of an association between CIN pauses and internally-generated slow wave events in sleeping non-human primates. Moreover, our method indicated that dendritic NaP and HCN currents were preferentially expressed in proximal dendrites. We validated the non-uniform distribution of NaP currents: pharmacologically; with two-photon imaging of dendritic back-propagating action potentials; and by demonstrating boosting of thalamic, but not cortical, inputs by NaP currents. Thus, the localization of active dendritic conductances in CIN dendrites mirrors the spatial distribution of afferent terminals and may promote their differential responses to thalamic vs. cortical inputs.
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