Endogenous Cholinergic Inputs and Local Circuit Mechanisms Govern the Phasic Mesolimbic Dopamine Response to Nicotine

doi:10.1371/journal.pcbi.1003183

Endogenous Cholinergic Inputs and Local Circuit Mechanisms Govern the Phasic Mesolimbic Dopamine Response to Nicotine

Figure 3

Model VTA responses to nicotine in vitro.

Left hand panels (A,C,E and left side of panel G) show the results on GABAergic input changes to VTA DA cells, while the panels on the right-hand side (B,D,F and right side of G) depict results on glutamatergic input increases to VTA DA cells in response to 1 µM nicotine for 2 min starting at t = 1 min. (A&B) Illustration of the simulated experimental situation during in vitro experiments. Grey shaded parts and black crosses show pharmacologically blocked transmission pathways, and the scissors illustrate the truncation of the input pathways in vitro. (C&D) Time course of GABAergic, , (C) and glutamatergic input, , (D) changes to VTA DA neurons during and after Nic exposure (black bar on top of the panels, Nic time-course shown in insets). The increase (green) and the decrease (magenta in C) of the input currents with respect to baseline are illustrated in both panels. (E&F) Maximal change of GABAergic (E) and glutamatergic input currents (F) as a function of the Nic concentration applied. The lines show the results of the model for control conditions (in green in both panels and magenta for decrease in panel E), with α4β2 nAChRs blocked (cyan in panel E, and green in panel F), and with α7 nAChRs blocked (green and magenta in panel E, orange in panel F). The squares show experimental results adapted from [19] (E) and [18] (F) for different experimental situations : control conditions - green squares; with α7 nAChR specific antagonist - orange squares; and with antagonist for non- α7 nAChRs - cyan squares. (G) Comparison of relative input changes between model and experiment for the case of 1 µM nicotine for 2 min. Model results are shown with shaded bars and experimental results with filled bars. Both, GABAergic- (left) and glutamatergic input changes (right) are shown for the three discussed cases : control conditions - green and magenta, α4β2 nAChR blocked - cyan, and α7 nAChR blocked - orange and magenta (experimental data adapted from [18], [19]; µM and in all panels, see Table 1 and Models section for other parameters).

doi: https://doi.org/10.1371/journal.pcbi.1003183.g003