Journal article
Striatal low-threshold spiking interneurons locally gate dopamine
Current biology, v 31(18), pp 4139-4147.e6
27 Sep 2021
PMID: 34302742
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The dorsomedial striatum (DMS) is a central hub supporting goal-directed learning and motor performance. Recent evidence has revealed unexpected roles for local inhibitory GABAergic networks in modulating striatal output and behavior.(1) The sparse low-threshold spiking interneuron subtype (LTSI), which exhibits robust reward-circumscribed population activity, is a bidirectional regulator of initial goal-directed learning.(2) Striatal dopamine signaling is a central reward-related neuromodulatory system mediating goal-directed action and performance, serving as a teaching signal,(3) facilitating synaptic plasticity,(4) and invigorating motor behaviors.(5) Given the dynamic modulation of LTSIs during goal-directed behavior, we hypothesized that they could provide a novel GABAergic mechanism of local striatal dopaminergic regulation to shape early learning. We provide anatomical evidence for close proximation of LTSI terminals and dopaminergic processes in striatum, suggesting that LTSIs directly control dopaminergic axon activity. Using in vitro fast scan cyclic voltammetry, we demonstrate that LTSIs directly attenuate optogenetically evoked dopamine via GABAB receptor signaling. In vivo, GRABDA dopamine sensor imaging shows that LTSIs strongly modulate striatal dopamine dynamics during operant learning, while pharmacological stabilization of dopamine via intra-striatal aripiprazole microinjection suppresses the effects of LTSI inhibition on learning. Together, these results uncover an unexpected function for LTSIs in gating striatal dopamine to facilitate goal-directed learning.
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Details
- Title
- Striatal low-threshold spiking interneurons locally gate dopamine
- Creators
- Elizabeth N. Holly - University of PennsylvaniaM. Felicia Davatolhagh - University of PennsylvaniaRodrigo A. Espana - Drexel UniversityMarc Fuccillo - University of Pennsylvania
- Publication Details
- Current biology, v 31(18), pp 4139-4147.e6
- Publisher
- Elsevier
- Number of pages
- 16
- Grant note
- F32 MH114506; R00MH099243; R01 MH118369 / NIMH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) Howard Hughes Medical Institute Gilliam Fellowship; Howard Hughes Medical Institute Whitehall Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000703803600006
- Scopus ID
- 2-s2.0-85115783081
- Other Identifier
- 991019167838604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology
- Cell Biology