Interval timing clock property in the rat granular retrosplenial cortex

Abstract

The rodent granular retrosplenial cortex (gRSC), densely interconnected with the hippocampal formation and the anterior thalamic nuclei, plays an important role in learning and memory. We had revealed that small pyramidal neurons in the superficial layers of the rat gRSC exhibit late-spiking (LS) firing properties. It has been suggested that neural circuits containing LS neurons can encode time intervals on the order of seconds, known as "interval timing". To test the possibility that the rat gRSC is involved in the processing of interval timing, we employed a trace fear conditioning paradigm in which the conditioned stimulus (CS) and the unconditioned stimulus (US) were temporally separated. First, we examined the effect of cytotoxic lesions made in the RSC prior to trace fear conditioning. We found that intact rats exhibited freezing behavior after CS tone presentation, whereas lesioned rats did not exhibit such freezing behavior. Next, we conducted in vivo chronic or acute recordings of neural activity from the rat gRSC in a test session conducted one week after the conditioning. In both recordings, we observed a distinct spike activity in which there was a transient increase in the firing rate around the presentation of the CS tone, followed by a rapid suppression and then ramping activity (a gradual elevation of the firing rate) until the next CS presentation. This "ramping activity" is thought to be one way in which interval timing is represented in the brain. Post stimulus histogram analysis revealed the existence of ramping activity in the gRSC, which reached its peak at various time intervals after the onset of the CS tone. Interestingly, this activity was specifically observed in response to the CS tone but not to the non-CS tone. Moreover, in naive rat gRSC (no trace fear conditioning), no such ramping activity was observed. These results indicate that gRSC neurons can encode time information on the order of tens to hundreds of seconds, integrating incoming sensory input with past memory traces.