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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 7
[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
Total Affiliations: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 10, n. 1 APR 28 2020.
Web of Science Citations: 0

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)

FAPESP's process: 16/17882-4 - Drug-resistant epilepsies: diagnostic challenges, associated comorbidities and new experimental approaches
Grantee:João Pereira Leite
Support type: Research Projects - Thematic Grants
FAPESP's process: 18/02303-4 - Study of the meso-cortico-limbic connectivity in animals submitted to early-life Status epilepticus and its relationship with psychiatric comorbidities
Grantee:Rafael Naime Ruggiero
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/18211-0 - Characterization and optogenetic control of the hippocampus-medial prefrontal cortex interplay during the post-learning sleep in an experimental model of early-life seizures
Grantee:Cleiton Lopes Aguiar
Support type: Scholarships in Brazil - Post-Doctorate