Acquisition and expression of fear memories are distinctly modulated along the dorsolateral periaqueductal gray axis of rats exposed to predator odor

• Cat odor induces avoidance and increases risk assessment in rats, as well as contextual fear conditioning.
• NMDA receptors within the dlPAG mediate both innate and contextual fear to predator odor.
• Acquisition, but not consolidation, of predator fear is mediated by rostral dlPAG NMDA receptors.
• Expression of predator-induced contextual fear is mediated by caudal dlPAG NMDA receptors.
• Innate and contextual fear to predator odor is differently mediated by rostro and caudal dlPAG.

The dorsolateral region of the midbrain periaqueductal gray (dlPAG) modulates both innate and conditioned fear responses. However, the contribution of the rostrocaudal portions of the dlPAG to defense reactions and aversive memories remains unclear. Here, we sought to investigate the effects of N-methyl-d-aspartate (NMDA) receptor blockade within rostral or caudal dlPAG of rats exposed to innate and learned fear to cat odor. For this, adult male Wistar rats were microinjected with the NMDA antagonist D-2-amino-5-phosphono-pentanoate (AP5; 3 or 6 nmol/0.2 μl) into the rostral or caudal dlPAG before and after the exposure to the cat odor or to the context paired with the predator odor. The results demonstrated that cat odor exposure induced unconditioned defensive behaviors as well as contextual fear. AP5 microinjected in the rostral dlPAG reduced the defensive responses to cat odor and impaired the acquisition, but not consolidation of contextual fear. On the other hand, AP5 infused within the caudal dlPAG promoted long-lasting reduction of contextual fear expression. Altogether, our data suggest that NMDA receptors mediate a functional dichotomy in the rostrocaudal axis of dlPAG regulating unconditioned and conditioned defensive reactions to predatory cues.