< Back to Article
Endogenous Cholinergic Inputs and Local Circuit Mechanisms Govern the Phasic Mesolimbic Dopamine Response to Nicotine
Figure 4
Model VTA responses to nicotine in vivo.
Panels on the left-hand side (A,C,E) show results of the direct stimulation scenario (
, 
µM, 
) and panels on the right-hand side (B,D,F) depict results for disinhibition (
, 
µM, 
). (A&B) Illustration of the simulated experimental situation in vivo. Note the difference in α4β2 nAChR distribution between the direct stimulation (A, 
) and the disinhibition case (B, 
). (C&E) Normalized DA (C) and GABA neuron activity (E) in response to the application of 1 µM nicotine in case of direct stimulation. The full lines show the time course of the normalized 
(C) and 
(E) for three different durations of nicotine exposure, 
(as indicated by the bar on top of C). The full and the dashed blue lines depict the responses for low (
µM) and high endogenous cholinergic input rates (
µM), respectively (
min). (D&F) Normalized DA (D) and GABAergic neuron activity (F) in response to 1 µM nicotine for 2 min in case of disinhibition. The full lines show the time course of the normalized 
(D) and 
(F) for three different maximal desensitization time constants of α4β2 nAChRs, 
(as indicated in the upper panel). The full and the dashed blue lines depict the responses for high (
µM) and low cholinergic input rates (
µM), respectively (
min). (G) Comparison of model results (purple and orange bars) and experimental data (green bars) on relative DA neuron activity changes in response to 1 µM nicotine. The maximal relative increase of DA activity in wild type (
min for direct stimulation; and 
min with 
min for disinhibition) and mutant mice is shown (experimental data adapted from [17]). (H) Comparison of the total duration of elevated DA neuron activity with respect to the duration of Nic application, 
. The duration of elevated activity is taken to be the time between the two points where 
attains half-of-maximum activity (as illustrated by arrows in C and D and depicted by square and circle, respectively). This duration is plotted for direct stimulation (purple) and disinhibition (orange).
doi: https://doi.org/10.1371/journal.pcbi.1003183.g004