The rostrodorsal periaqueductal gray influences both innate fear responses and acquisition of fear memory in animals exposed to a live predator

• Published in: Brain Structure and Function Vol. 224; no. 4; pp. 1537 - 1551
• Main Authors: de Andrade Rufino, Rodrigo, Mota-Ortiz, Sandra Regina, De Lima, Miguel Antonio Xavier, Baldo, Marcus Vinicius C., Canteras, Newton Sabino
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2019; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Cytotoxicity; Fear; Learning; Muscimol; Neuroethology; Neurology; Neurosciences; Nitric oxide; Nitric-oxide synthase; Original Article; Periaqueductal gray area; Risk assessment; Tonic immobility; Fear memory; Innate fear; Defensive behavior; Nitric oxide
• ISSN: 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-019-01852-6

A few studies have evaluated the behavioral roles of the periaqueductal gray (PAG) in animals facing ethologically relevant threats. Exposure to a live cat induces striking activation in the rostrodorsal and caudal ventral PAG. In the present investigation, we first showed that cytotoxic lesions of the rostrodorsal and caudal ventral PAG had similar effects on innate fear responses during cat exposure, practically abolishing freezing and increasing risk assessment responses. Conversely, rostrodorsal PAG lesions but not caudal ventral lesions disrupted learned contextual fear responses to cat exposure. Next, we examined how muscimol inactivation of the rostrodorsal PAG at different times (i.e., during, immediately after and 20 min after cat exposure) influences learned contextual fear responses, and we found that inactivation of the rostrodorsal PAG during or immediately after cat exposure but not 20 min later impaired contextual fear learning. Thus, suggesting that the rostrodorsal PAG is involved in the acquisition, but not the consolidation, of contextual fear memory to predatory threat. Notably, the dosolateral PAG contains a distinct population of neurons containing the neuronal nitric oxide synthase (nNOS) enzyme, and in the last experiment, we investigated how nitric oxide released in rostrodorsal PAG influences contextual fear memory processing. Accordingly, injection of a selective nNOS inhibitor into the rostrodorsal PAG immediately after cat exposure disrupted learned contextual responses. Overall, the present findings suggest that the acquisition of contextual fear learning is influenced by an optimum level of dorsal PAG activation, which extends from during to shortly after predator exposure and depends on local NO release.