Endogenous Cholinergic Inputs and Local Circuit Mechanisms Govern the Phasic Mesolimbic Dopamine Response to Nicotine
Figure 5
Predicted dynamics of the DA neuron population in the VTA in response to varying cholinergic input rates and Nic concentrations in case of direct stimulation (A,D) and disinhibition (B,E).
Nic was applied for 10 min in the direct stimulation scenario, and for 2 min in the disinhibition scenario, whereas the endogenous ACh input rate is modeled to be constant (see text). (A&B) Temporal dynamics of DA neuron activity in response to 1 µM nicotine and varying endogenous cholinergic input rates (ACh range: 0.1-blue lines, 0.5, 1.0, 1.5, 1.77-red lines, 2.0 µM). (C) Maximal increase of DA activity in response to 1.0 µM Nic as a function of the cholinergic input rate (,
). (D&E) Temporal dynamics of DA activity in response to 0.5 µM (blue lines) and 3 µM nicotine (red lines) in case of direct stimulation (D,
,
µM,
,
), or disinhibition (E,
,
µM,
,
). (F) The maximal DA response as a function of applied Nic concentration is depicted for direct stimulation (orange line) and disinhibition (purple line). Data point (green) adapted from [17].