Wong et al., 2019 used a sensory preconditioning protocol to examine how sensory and fear memories are integrated in the rat medial temporal lobe. In this protocol, rats integrate a sound-light (sensory) memory that forms in stage 1 with a light-shock (fear) memory that forms in stage 2 to generate fear responses (freezing) across test presentations of the sound in stage 3. Here, we advance this research by showing that (1) how/when rats integrate the sound-light and light-shock memories (online in stage 2 or at test in stage 3) changes with the number of sound-light pairings in stage 1; and (2) regardless of how/when it occurs, the integration requires communication between two regions of the medial temporal lobe: the perirhinal cortex and basolateral amygdala complex. Thus, ‘event familiarity’ determines how/when sensory and fear memories are integrated but not the circuitry by which the integration occurs: this remains the same.

The neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides and their receptors are expressed at high levels in pain-responsive neurons from the periphery to the brain making them attractive therapeutic targets. However, drugs targeting these pathways individually did not relieve pain in clinical trials. Since Substance P and CGRPα are extensively co-expressed, we hypothesized that their simultaneous inhibition would be required for effective analgesia. We therefore generated Tac1 and Calca double knockout (DKO) mice and assessed their behavior using a wide range of pain-relevant assays. As expected, Substance P and CGRPα peptides were undetectable throughout the nervous system of DKO mice. To our surprise, these animals displayed largely intact responses to mechanical, thermal, chemical, and visceral pain stimuli, as well as itch. Moreover, chronic inflammatory pain and neurogenic inflammation were unaffected by loss of the two peptides. Finally, neuropathic pain evoked by nerve injury or chemotherapy treatment was also preserved in peptide-deficient mice. Thus, our results demonstrate that even in combination, Substance P and CGRPα are not required for the transmission of acute and chronic pain.