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Cholinergic modulation of striatal nitric oxide-producing interneurons
Alexandria E Melendez-Zaidi1,2,3, Harini Lakshminarasimhah1, Dalton James Surmeier1
1Department of Physiology, Feinberg School of Medicine, Chicago, IL, USA.
The European Journal of Neuroscience
|July 25, 2019
Summary
Researchers uncovered how cholinergic interneurons control striatal low-threshold spike interneurons (LTSIs). Cholinergic signals, via M1 and M4 receptors, modulate LTSIs, influencing striatal circuits during salient stimuli.
Area of Science:
- Neuroscience
- Cellular Neuroscience
- Systems Neuroscience
Background:
- Striatal GABAergic interneurons, specifically low-threshold spike interneurons (LTSIs), are crucial for striatal function.
- The precise drivers of LTSIs activity remain incompletely understood.
Purpose of the Study:
- To elucidate the afferent pathways and modulatory mechanisms controlling LTSIs.
- To investigate the role of cholinergic interneurons in LTSIs activity.
Main Methods:
- Monosynaptic rabies virus mapping (msRVm) in transgenic mice.
- Electrophysiological recordings and optogenetic manipulations.
- Utilized mice expressing Cre recombinase or fluorescent reporters in LTSIs.
Main Results:
- LTSIs share similar afferent connections with cholinergic interneurons, notably from the parafascicular nucleus and cingulate cortex.
- Thalamic stimulation inhibited LTSIs via a dual pathway involving GABAergic transmission and M4 muscarinic receptors, mediated by cholinergic interneurons.
- Cholinergic interneurons tonically excited LTSIs through M1 muscarinic receptors.
Conclusions:
- Cholinergic modulation intricately controls LTSIs activity, integrating phasic and tonic signals.
- This coordinated cholinergic input primes LTSIs for rhythmic bursting, potentially reconfiguring striatal circuits in response to environmental stimuli.
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