(A) For experiments described in this figure mice were infected across all cortical depths bilaterally in binocular V1 (green). During the same surgical implantation procedure VEP recording electrodes were also positioned in layer 4 and chronically fixed. (B) Mice (P45-60) were infected and implanted with electrodes and then left for 3 weeks for the AAV9 viral vector to reach maximal expression, after which they underwent habituation to head-fixation and a gray screen for two consecutive days. Following this, on experimental day 0, mice were presented with an Xo phase-reversing sinusoidal grating stimulus separately to the left and right eye. VEPs were recorded from each hemisphere in order to determine ocular dominance in binocular V1. Mice were then removed from the recording apparatus and, CNO was delivered systemically half an hour prior to undertaking the same recording procedure, this time using an orthogonal X + 90° visual stimulus. (C) As is well documented, responses in V1 to stimuli viewed through the contralateral eye (blue) were greater in magnitude than those elicited through the ipsilateral eye (yellow), as measured here by VEP magnitude. After application of CNO (red outlines), VEP magnitude dramatically increased. (D) This increase was scaled such that the ratio of Contralateral:Ipsilateral VEP magnitude was maintained before (white) and after CNO (red). (E) In a second group of mice, a similar experimental protocol was observed prior to measuring ocular dominance by recording VEPs in each hemisphere elicited by an Xo stimulus through each eye. One hemisphere was then selected and the contralateral eye was sutured closed. After 7 days of monocular deprivation, the eye was opened and VEPs driven through either eye were again recorded, this time elicited by an X + 60° stimulus. Mice were then systemically injected with CNO and, half an hour later, VEPs driven through either eye were recorded, this time elicited by an X - 60° stimulus. (F) After the adult mice underwent 7 days of MD, there was a significant potentiation of the V1 response to visual input through the ipsilateral eye (yellow). After application of CNO (red outlines), VEPs driven through each eye were elevated in magnitude, but again the increase in VEP magnitude was scaled. (G) As a result of open eye potentiation after MD, the OD ratio shifted dramatically from the contralateral bias of pre MD (white) to an almost equal cortical response through contralateral and ipsilateral eyes (black). This shifted ratio was unaffected by hM4Di-mediated inactivation of putative fast-spiking inhibitory neurons during CNO application (red), indicating that the expression of OD and its shift as a result of MD in adult mice do not require fast-spiking inhibition. Significant comparisons are labeled with an asterisk and non-significant comparisons with n.s. throughout. Error bars are standard error of the mean (S.E.M.).