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

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...

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Principais autores: Lopes-Aguiar, Cleiton, Ruggiero, Rafael N., Rossignoli, Matheus T., Esteves, Ingrid de Miranda, Peixoto-Santos, José Eduardo, Romcy-Pereira, Rodrigo Neves, Leite, João P.
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Idioma:English
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schizophrenia
mental disorders - treatment
ketamine
long-term potentiation
neural circuits
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/28835
https://doi.org/10.1038/s41598-020-63979-5
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spelling ri-123456789-288352021-07-09T22:32:55Z Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo Lopes-Aguiar, Cleiton Ruggiero, Rafael N. Rossignoli, Matheus T. Esteves, Ingrid de Miranda Peixoto-Santos, José Eduardo Romcy-Pereira, Rodrigo Neves Leite, João P. schizophrenia mental disorders - treatment ketamine long-term potentiation neural circuits 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. 2020-04-28T19:46:39Z 2020-04-28T19:46:39Z 2020-04-28 article LOPES-AGUIAR, C. et al. Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo. Scientific Reports, [S. l.], v. 10, p. 7167, abr. 2020. https://repositorio.ufrn.br/jspui/handle/123456789/28835 https://doi.org/10.1038/s41598-020-63979-5 en application/pdf
institution Repositório Institucional
collection RI - UFRN
language English
topic schizophrenia
mental disorders - treatment
ketamine
long-term potentiation
neural circuits
spellingShingle schizophrenia
mental disorders - treatment
ketamine
long-term potentiation
neural circuits
Lopes-Aguiar, Cleiton
Ruggiero, Rafael N.
Rossignoli, Matheus T.
Esteves, Ingrid de Miranda
Peixoto-Santos, José Eduardo
Romcy-Pereira, Rodrigo Neves
Leite, João P.
Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
description 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.
format article
author Lopes-Aguiar, Cleiton
Ruggiero, Rafael N.
Rossignoli, Matheus T.
Esteves, Ingrid de Miranda
Peixoto-Santos, José Eduardo
Romcy-Pereira, Rodrigo Neves
Leite, João P.
author_facet Lopes-Aguiar, Cleiton
Ruggiero, Rafael N.
Rossignoli, Matheus T.
Esteves, Ingrid de Miranda
Peixoto-Santos, José Eduardo
Romcy-Pereira, Rodrigo Neves
Leite, João P.
author_sort Lopes-Aguiar, Cleiton
title Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
title_short Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
title_full Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
title_fullStr Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
title_full_unstemmed Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
title_sort long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
publishDate 2020
url https://repositorio.ufrn.br/jspui/handle/123456789/28835
https://doi.org/10.1038/s41598-020-63979-5
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