Figure 3.

Postnatal suppression of DISC1 expression in the prefrontal cortex (PFC) impairs developmental synaptic GABA function. (a) Immunohistochemical analysis with antibodies against GABA_A receptor α2 subunits (red) and gephyrin, a GABA synaptic scaffold protein (green), in developing pyramidal neurons (blue) of the medial PFC in mice with postnatal knockdown of DISC1 at P14. Reduction of colocalization of GABA_A receptor α2 subunits and gephyrin are observed in postnatal DISC1 knockdown mice. Scale bar, 10 µm. n = 5 neurons per condition. (b) Immunohistochemical analysis with antibodies against vesicular GABA transporter (vGAT, a presynaptic marker, indicated in red) and gephyrin (a GABA synaptic scaffold protein, indicated in green), in the developing pyramidal neurons (blue) of the medial PFC in mice with postnatal knockdown of DISC1 and control mice at P14. No changes in the number of gephyrin puncta and colocalization of vGAT and gephyrin are observed in postnatal DISC1 knockdown mice compared to control mice. Scale bar, 10 µm. n=5 neurons per condition. (c, d) Acute brain slice electrophysiology recordings from P14 mice show that postnatal suppression of DISC1 depresses GABAergic transmission. Representative traces depicting GABA-mediated miniature postsynaptic currents (GABA-mediated mPSCs) from each condition are shown. Summary graphs showing the amplitude of GABA-mediated mPSCs are decreased by postnatal DISC1 suppression, while DISC1 suppression does not affect on mPSCs frequency. All recordings were performed in the presence of D,L AP5 (100 µM), NBQX (10 µM), and TTX (1 µM). n = 10–15 neurons per condition. *P < 0.05 determined by Student’s t test (a, d).