Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

Autor(es)

Lopes-Aguiar, Cleiton ^[1] ; Ruggiero, Rafael N. ^[2] ; Rossignoli, Matheus T. ^[2] ; Esteves, Ingrid de Miranda ^[2] ; Peixoto-Santos, Jose Eduardo ^[3] ; Romcy-Pereira, Rodrigo N. ^[4] ; Leite, Joao P. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, Nucleo Neurociencias, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, BR-14049900 Ribeirao Preto - Brazil

^[3] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, BR-04039032 Sao Paulo, SP - Brazil

^[4] Univ Fed Rio Grande do Norte, Brain Inst, BR-59056450 Natal, RN - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 APR 28 2020.
• Citações Web of Science: 0

Resumo

N-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related to schizophrenia, particularly in the hippocampus and the prefrontal cortex. It has been shown that prior long-term potentiation (LTP) occluded the increase of synaptic efficacy in the hippocampus-prefrontal cortex pathway induced by MK-801, a non-competitive NMDAr antagonist. However, it is not clear whether LTP could also modulate aberrant oscillations and short-term plasticity disruptions induced by NMDAr antagonists. Thus, we tested whether LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma cross-frequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits. (AU)

• Processo FAPESP: 16/17882-4 - Epilepsias farmacorresistentes: desafios diagnósticos, estudo das comorbidades associadas e novas abordagens experimentais
• Beneficiário: João Pereira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/02303-4 - Estudo da conectividade da circuitaria meso-cortico-limbica em animais submetidos a Status epilepticus durante o desenvolvimento e sua relação com comorbidades psiquiátricas
• Beneficiário: Rafael Naime Ruggiero
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/18211-0 - Caracterização e controle optogenético da comunicação hipocampo-córtex pré-frontal medial durante sono subsequente ao aprendizado em um modelo experimental de crises na infância
• Beneficiário: Cleiton Lopes Aguiar
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado