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

Author(s)

Rufino, Rodrigo de Andrade ^[1] ; Mota-Ortiz, Sandra Regina ^[1] ; Xavier De Lima, Miguel Antonio ^[1] ; Baldo, Marcus Vinicius C. ^[2] ; Canteras, Newton Sabino ^{[1, 3]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Ave Lineu Prestes 2415, BR-05508900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Brain Structure & Function; v. 224, n. 4, p. 1537-1551, MAY 2019.
• Web of Science Citations: 1

Abstract

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 20min 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 20min 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. (AU)

• FAPESP's process: 14/02540-5 - The role the hypothalamic defensive circuit and its main ascending targets on residual fear responses of animals bearing PAGDL lesions during predator exposure
• Grantee: Rodrigo de Andrade Rufino
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/05432-9 - Neural bases of fear and aggression
• Grantee: Newton Sabino Canteras
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/10389-0 - Involvement of prefrontal cortex areas and their targets in fear memory processing: a study with drug and optogenetic techniques
• Grantee: Miguel Antonio Xavier de Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral