A dopamine-acetylcholine cascade: simulating learned and lesion-induced behavior of striatal cholinergic interneurons

Journal of Neurophysiology
Can Ozan Tan, Daniel Bullock

Abstract

The giant cholinergic interneurons of the striatum are tonically active neurons (TANs) that respond with pauses to appetitive and aversive cues and to novel events. Whereas tonic activity emerges from intrinsic properties of these neurons, glutamatergic inputs from intralaminar thalamic nuclei and dopaminergic inputs from midbrain are required for genesis of pause responses. No prior computational models encompass both intrinsic and synaptically gated dynamics. We present a mathematical model that robustly accounts for behavior-related electrophysiological properties of TANs in terms of their intrinsic physiological properties and known afferents. In the model, balanced intrinsic hyperpolarizing and depolarizing currents engender tonic firing and glutamatergic inputs from thalamus (and cortex) both directly excite and indirectly inhibit TANs. If this inhibition, probably mediated by GABAergic nitric oxide synthase interneurons, exceeds a threshold, a persistent K+ conductance current amplifies its effect to generate a prolonged pause. Dopamine (DA) signals modulate both the intrinsic mechanisms and the external inputs of TANs. Simulations revealed that many learning-dependent behaviors of TANs, including acquired pauses to task...Continue Reading

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Citations

Jun 5, 2010·Journal of Cognitive Neuroscience·F Gregory Ashby, Matthew J Crossley
Sep 23, 2010·Neural Computation·Hiroyuki Nakahara, Sivaramakrishnan Kaveri
Sep 14, 2012·Neural Computation·Benjamin J H SmithElie Allouis
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Dec 24, 2010·Bipolar Disorders·William R Marchand, Deborah Yurgelun-Todd
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Jun 23, 2016·Journal of Neurogenetics·Kristin M Scaplen, Karla R Kaun
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Sep 6, 2018·The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences·Layla DangJessica R Petok
Sep 4, 2021·Frontiers in Aging Neuroscience·Sumonto MitraJaan-Olle Andressoo

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