Extended Data Fig. 7: ‘Desensitization’ response of nAChRs plays a limited role in modifying phasic DA release in a computational model during multiphasic ChI activity.
From: An axonal brake on striatal dopamine output by cholinergic interneurons
a, Coincident phasic DA neuron firing (blue) and multiphasic ChI activity (yellow) with (left) or without (right) initial excitation in ChIs. Inset, firing rates normalized to baseline rates. b, Phasic DA release was modified by ChI activity (compared to no ChI effects, blue) both with (solid green line) and without (dashed green line) a ‘desensitization’ component in the model (obtained from Fig. 4j,l) for DLS (upper) and NAcc (lower). Background levels of tonic suppression of DA output by ChIs included in the model were 0, 50 and 100%. Inclusion of a dynamic desensitization-like component in the model impacted on phasic DA release only when there was initial ChI excitation (left), and only in DLS, acting to slightly increase phasic DA release by preventing nAChRs from inhibiting DA release during a rebound activity phase in ChIs. The effect is prominent in DLS (upper) than in NAcc (lower), consistent with the stronger ChI-induced inhibition of DA release in DLS than NAcc. As expected, excluding a dynamic desensitization-like component from the model did not affect DA release when the initial excitation was absent because there was no initial increase in nAChR activation.
