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. 2021 Jul 29;47(3):641–651. doi: 10.1038/s41386-021-01107-1

Fig. 5. Activation of IPN GABAergic neurons during withdrawal controls anxiety-like avoidance of open-arm exploration in the elevated plus maze.

Fig. 5

A To record GCaMP responses during EPM exploration, GAD2:Cre mice had GCaMP and optic fibers implanted into the IPN and underwent 6 weeks of chronic nicotine treatment. Behavior in the EPM was recorded prior to and following 48 h spontaneous withdrawal from nicotine. B–D Mice in withdrawal significantly decreased open-arm exploration and increased time spent in the closed-arms but did not change total arm entries compared to when they were not in withdrawal. Prior to withdrawal, GCaMP activity did not change in the closed- (blue shaded E) vs open-arm (pink shaded E, F), whereas a significant increase in GCaMP signal was observed during exploration of the open-arm (pink shaded G) compared to the closed-arm (blue shaded G) when mice were in nicotine withdrawal (H). Optical silencing of IPN GAD2+ neurons in NpHR mice significantly increased time spent in the open-arms compared to eYFP mice following mecamylamine challenge and reduced time spent in the closed-arms (I, J). Total arm entries were not different between NpHR and eYFP mice (K). NIC chronic nicotine, Wd 48 h nicotine withdrawal, MEC mecamylamine, SAL saline.