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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Brain Structure & Function; v. 224, n. 4, p. 1537-1551, MAY 2019.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 14/02540-5 - Investigação do papel do circuito de defesa e seus alvos ascendentes na elaboração das respostas de medo em animais portadores de lesão da coluna dorsolateral da substância cinzenta periaquedutal
• Beneficiário: Rodrigo de Andrade Rufino
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/53390-5 - Avaliacao da participacao da porcao rostrodorsal da substancia cinzenta periaquedutal nas respostas contextuais de defesa ao ambiente previamente relacionado ao predador.
• Beneficiário: Sandra Regina Mota Ortiz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/05432-9 - Bases neurais do medo e agressão
• Beneficiário: Newton Sabino Canteras
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/10389-0 - Investigação do envolvimento das áreas do córtex pré-frontal e de seus alvos no processamento da memória de medo: estudo com técnicas fármaco e optogenéticas
• Beneficiário: Miguel Antonio Xavier de Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado