Optogenetic suppression of ventral tegmental area (VTA) dopaminergic neurons evokes place avoidance.

(A) Atlas schematic shows chronically implanted animals with optic fiber and tetrodes in the VTA or hippocampal CA1 region. Middle panels: yellow fluorescent protein (YFP) expression, tyrosine hydroxylase (TH) staining, and their overlay in VTA of TH::Cre rats injected with Cre-inducible light-activated chloride channel (iC++) adeno-associated virus. The right image shows a confocal image of the VTA with YFP, TH, and DAPI overlaid. (B) High-magnification confocal images of YFP expression and TH staining and their colocalization in the VTA. Right image shows a confocal 3D render of the VTA neuron with YFP, TH, and DAPI overlay. (C) Raster plot from 40 repetitions (above) and firing frequency (below) of optically evoked time-locked inhibition of a VTA slow-spiking cell. Time 0 indicates the delivery of the first train of the stimulation protocol. (D) Behavioral setup of laser application (marked with a blue dashed square) in the south and west arms of the rectangular-shaped linear track. Black circles indicate pellets delivery. The ratio of the passes through the southwest (SW) and northeast (NE) corners (marked with black dashed squares) was compared between control and photoinhibition sessions. (E) Light-induced place avoidance throughout 5 consecutive days, n = 5 rats, paired t test, day 1, t(4) = 3.545, *p = 0.024; day 2, t(4) = 6.146, **p = 0.004; day 3, t(4) = 2.978, *p = 0.041; day 4, t(4) = 5.423, **p = 0.006; day 5, t(4) = 4.501, *p = 0.011. Error bars, mean ± SEM. Files dataset is available at Figshare public repository in Tsanov 2016 data / iC++ electrophysiology and iC++ immunohistology folders https://figshare.com/s/b86a9a111353ba04bd32.