Temporal association activates projections from the perirhinal cortex and ventral CA1 to the prelimbic cortex and from the prelimbic cortex to the basolateral amygdala

In temporal associations, the prelimbic cortex (PL) has persistent activity during the interval between the conditioned stimulus (CS) and the unconditioned stimulus (US), which maintains a CS representation. Regions cooperating for this function or encoding the CS before the interval could neuroanatomically connect to the PL, supporting learning. The basolateral amygdala (BLA) has CS- and US-responsive neurons, convergently activated. The PL could directly project to the BLA to associate the transient CS memory with the US. We investigated the neural circuit supporting temporal associations using the CFC-5s task, in which a 5-second interval separates the contextual CS from the US. Injecting retrobeads, we quantified c-Fos in PL- or BLA-projecting neurons from 9 regions after CFC-5s or contextual fear conditioning (CFC), in which CS/US overlap. The CFC-5s activated ventral CA1 (vCA1) and perirhinal cortex (PER) neurons projecting to the PL, and PL neurons projecting to BLA. Both CFC-5s and CFC activated vCA1 and lateral entorhinal (LEC) neurons projecting to BLA, and BLA neurons projecting to PL. Both conditioning activated the PER, LEC, cingulate and infralimbic cortices, nucleus reuniens, and ventral subiculum. Results added new relevance to the PER[->]PL projection and showed that the PL/BLA are reciprocally functionally connected in CFC-5s.