Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons
- Hebrew University of Jerusalem, Israel
Abstract
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.
Data availability
Tables with all data points used in the figures is available at Open Science Framework: https://osf.io/yxej3/
Article and author information
Author details
Funding
European Research Council (646886)
- Joshua A Goldberg
Israel Science Foundation (2051/20)
- Hagai Bergman
Deutsche Forschungsgemeinschaft (CRC TRR295)
- Hagai Bergman
Israel Science Foundation (154/14)
- Joshua A Goldberg
Israel Science Foundation (155/14)
- Joshua A Goldberg
U.S.-Israel Binational Science Foundation (2017020)
- Joshua A Goldberg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental protocols were conducted in accordance with the NationalInstitutes of Health Guide for the Care and Use of Laboratory Animals, and with the Hebrew University guidelines for the use and care of laboratory animals in research. The experiments adhered to, received prior written approval from and were supervised by the Institutional Animal Care and Use Committee of the Faculty of Medicine, under protocols: MD-16-13518-4 (H.B.) and MD-18-15657-3 (J.A.G.).
Copyright
© 2022, Oz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons
eLife 11:e76039.
https://doi.org/10.7554/eLife.76039
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