1. Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo
- Author
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Matheus Teixeira Rossignoli, Rafael N. Ruggiero, Rodrigo Neves Romcy-Pereira, José Eduardo Peixoto Santos, Ingrid de Miranda Esteves, João Pereira Leite, and Cleiton Lopes-Aguiar
- Subjects
0301 basic medicine ,Male ,ketamine ,Long-Term Potentiation ,Hippocampus ,Prefrontal Cortex ,lcsh:Medicine ,Local field potential ,Receptors, N-Methyl-D-Aspartate ,Neural circuits ,Article ,03 medical and health sciences ,Glutamatergic ,0302 clinical medicine ,LTP induction ,Animals ,Cognitive Dysfunction ,Rats, Wistar ,Prefrontal cortex ,lcsh:Science ,long-term potentiation ,neural circuits ,Multidisciplinary ,Chemistry ,musculoskeletal, neural, and ocular physiology ,lcsh:R ,Long-term potentiation ,Rats ,schizophrenia ,030104 developmental biology ,nervous system ,Synaptic plasticity ,Schizophrenia ,NMDA receptor ,Ketamine ,lcsh:Q ,Neuroscience ,030217 neurology & neurosurgery ,mental disorders - treatment - Abstract
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.
- Published
- 2020