A Variable Oscillator Underlies the Measurement of Time Intervals in the Rostral Medial Prefrontal Cortex during Classical Eyeblink Conditioning in Rabbits

Abstract

We were interested in determining whether rostral medial prefrontal cortex (rmPFC) neurons participate in the measurement of conditioned stimulus– unconditioned stimulus (CS-US) time intervals during classical eyeblink conditioning. Rabbits were conditioned with a delay paradigm consisting of a tone as CS. The CS started 50, 250, 500, 1000, or 2000msbefore and coterminated with an air puff (100 ms) directed at the cornea as the US. Eyelid movements were recorded with the magnetic search coil technique and the EMG activity of the orbicularis oculi muscle. Firing activities of rmPFC neurons were recorded across conditioning sessions. Reflex and conditioned eyelid responses presented a dominant oscillatory frequency of 12 Hz. The firing rate of each recorded neuron presented a single peak of activity with a frequency dependent on the CS-US interval (i.e., 12 Hz for 250 ms, 6 Hz for 500 ms, and 3 Hz for 1000 ms). Interestingly, rmPFC neurons presented their dominant firing peaks at three precise times evenly distributed with respect to CS start and also depending on the duration of the CS-US interval (only for intervals of 250, 500, and 1000 ms). No significant neural responses were recorded at very short (50 ms) or long (2000 ms) CS-US intervals. rmPFC neurons seem not to encode the oscillatory properties characterizing conditioned eyelid responses in rabbits, but are probably involved in the determination of CS-US intervals of an intermediate range (250 –1000 ms). We propose that a variable oscillator underlies the generation of working memories in rabbits.