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

Figure 2

Nicotinic acetylcholine receptor model responses to nicotine and acetylcholine.

Response properties of α4β2 (panels A,C,E) and α7 nAChRs (panels B,D,E). (A&B) Dynamics of α4β2- (A) and α7-containing nAChRs (B) in response to Nic. The dynamics of the activation, a, (purple lines) and sensitization, s, (orange lines) are shown during and after the exposure to a constant Nic concentration of 100 µM for 200 ms starting at ms. The normalized receptor activation, , is shown in blue and is proportional to the actual current. The inset shows the dynamics of the same variables on a longer time scale. (C&D) Dose-response curves of α4β2- (C) and α7-containing nAChRs (D) in response to Nic and ACh. The peak current mediated by the receptor during a 200 ms exposure to the respective agonist concentration is shown. The responses to Nic (ACh) are depicted in blue (red). The arrows indicate physiologically relevant nicotine concentrations [11], [31]. The half-maximum effective concentrations for ACh-evoked responses are indicated by the dotted black lines. (E) Reduction of the half-maximum response evoked by ACh in the presence of 0.5 µM Nic. The half-maximum effective concentration of the peak current in the absence of Nic is µM for α4β2, and µM for α7 nAChRs (green bars, see C and D). The red bars show the peak current in response to the same ACh concentration in the presence of a constant concentration of µM. See Table 1 for parameters.

doi: https://doi.org/10.1371/journal.pcbi.1003183.g002