Fig 1. GABA_B1a^-/- mice exhibit deficits in executing an operant conditioning task.

(A) Mice were chronically implanted with stimulating (St.) and recording (Rec.) electrodes in the Schaffer collaterals/commissural pathway (Sch.) and the CA1 area, respectively. Representative photomicrographs illustrating the location (arrows) of recording (left) and stimulating (right) electrodes in post-experimental tissue are shown at the top. Calibration bars: 500 μm. (B) Mice were trained in a Skinner box to press a lever to obtain a food pellet. For operant conditioning we used two paradigms of increasing difficulty. In the first paradigm (Fixed-ratio of 1:1) mice had to press the lever ≥ 20 times per 20 min session for two successive sessions to successfully complete the task (criterion). In the second paradigm (Light/Dark), lever presses were rewarded only when a light bulb was switched on. Lever presses while the bulb was off were punished with a time penalty of 10 s during which the bulb would not turn on. In this case the animal had to press the lever at least the same number of times during the light and the dark periods for two successive sessions to successfully complete the task (criterion). (C) Performance of mice during 6 days of training with the 1:1 ratio schedule. WT mice (open circles) pressed the lever significantly more (P ≤ 0.02) and reached the criterion (arrow) in fewer sessions than GABA_B1a^-/- mice (closed circles). All WT mice but only 40% of the GABA_B1a^-/- mice successfully completed the task within 6 sessions (right panel). (D) Analysis of evoked fEPSP at the CA3-CA1 synapses during operant conditioning. The fEPSP slopes of WT mice were significantly (P < 0.02) larger than those of GABA_B1a^-/- mice during the 2^nd session. Representative fEPSPs recorded during the indicated sessions (1 and 2) are shown at the top. E, Performance of mice during 6 days of training in the light/dark test. WT mice performed significantly better than GABA_B1a^-/- mice (*, P = 0.03; **, P ≤ 0.006) and reached the criterion by the 4^th session (arrow). GABA_B1a^-/- mice failed to reach the criterion. The light/dark coefficient was calculated as follows: (number of lever presses during the light period—number of lever presses during the dark period) / total number of lever presses.