Simulating Effects of Learning and Lesions with a Model of Intrinsic and Synaptically Gated Responses of Striatal Cholinergic Interneurons


Show simple item record Tan, Can Ozan en_US Bullock, Daniel en_US 2011-11-14T18:20:40Z 2011-11-14T18:20:40Z 2006-10 en_US
dc.description.abstract The giant cholinergic interneurons of the striatum are tonically active neurons (TANs) that respond with characteristic pauses to novel events and to appetitive and aversive conditioned stimuli. Fluctuations in acetylcholine release by TANs modulate performance- and learning-related dynamics in the striatum. Whereas tonic activity emerges from intrinsic properties of these neurons, glutamatergic inputs from thalamic centromedian-parafascicular nuclei, and dopaminergic inputs from midbrain, are required for the generation 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 the latter inhibition, presumably mediated by GABAergic interneurons, exceeds a threshold, its effect is amplified by a KIR current to generate a prolonged pause. In the model, the intrinsic mechanisms and external inputs are both modulated by learning-dependent dopamine (DA) signals and our simulations revealed that many learning-dependent behaviors of TANs are explicable without recourse to learning-dependent changes in synapses onto TANs. The "teaching signal" that modulates reinforcement learning at cortico-striatal synapses may be a sequence composed of an adaptively scaled DA burst, a brief ACh burst, and a scaled ACh pause. Such an interpretation is consistent with recent data on cholinergic control of LTD of cortical synapses onto striatal spiny projection neurons. en_US
dc.description.sponsorship National Science Foundation (SBE-354378); Higher Education Council of Turkey; Canakkale Onsekiz Mart University of Turkey en_US
dc.publisher Boston University Center for Adaptive Systems and Department of Cognitive and Neural Systems en_US
dc.relation.ispartofseries BU CAS/CNS Technical Reports;CAS/CNS-TR-2006-006 en_US
dc.rights Copyright 2008 Boston University. Permission to copy without fee all or part of this material is granted provided that: 1. The copies are not made or distributed for direct commercial advantage; 2. the report title, author, document number, and release date appear, and notice is given that copying is by permission of BOSTON UNIVERSITY TRUSTEES. To copy otherwise, or to republish, requires a fee and / or special permission. en_US
dc.subject Tonically active neuron en_US
dc.subject Basal ganglia en_US
dc.subject Thalamostriatal en_US
dc.subject Reinforcement learning en_US
dc.subject Dopamine en_US
dc.subject Acetylcholine en_US
dc.title Simulating Effects of Learning and Lesions with a Model of Intrinsic and Synaptically Gated Responses of Striatal Cholinergic Interneurons en_US
dc.type Technical Report en_US
dc.rights.holder Boston University Trustees en_US

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