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Characterization and optogenetic control of the hippocampus-medial prefrontal cortex interplay during the post-learning sleep in an experimental model of early-life seizures

Grant number: 14/18211-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2014
Effective date (End): December 27, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:João Pereira Leite
Grantee:Cleiton Lopes Aguiar
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):15/25275-8 - Optogenetic investigation of hippocampal ripples influence on prefrontal circuits during contextual fear memory formation, BE.EP.PD

Abstract

The underlying mechanisms of the epileptic encephalopathies are still poorly understood. A key feature of this condition is the preferential incidence of epileptic discharges during sleep, which is typically not mirrored in any existing animal models. The sharp-wave ripple complexes (SWRs), which occur during slow-wave sleep, seem to support information outflow from the hippocampus to the neocortex. Interestingly, intact SWRs are also required to spatial memory consolidation. Electrophysiological studies in vitro have suggested that in the hippocampus of adult rats submitted to status epilepticus by pilocarpine the SWRs are replaced by higher frequencies events (250-600Hz), termed fast-ripples (FRs). Our hypothesis is that the switch from SWRs to FRs also strikes adult rats previously submitted to early-life seizures. This condition could lead to aberrant information outflow from CA1 to the medial prefrontal cortex (mPFC) during sleep, yielding a poor noise-to-signal ratio and spatial working memory disruptions. Here, we will use extracellular recordings of individual cells, local field potentials and evoked post-synaptic potentials in freely behaving rats (1) to probe the role of SWRs and FRs on the synaptic plasticity and information in the CA1-mPFC circuit; (2) to examine how these events modulate working memory in both intact rats and in subjects previously submitted to early-life seizures. We will test whether the selective inhibition of mPFC principal cells just after FR events in CA1 can mitigate working memory disruptions in the animals previously submitted to early-life seizures. Finally, we will implement a closed-loop strategy to detect SWRs and FRs events in CA1 and optogenetically inhibit mPFC principal cells activity to directly test the relevance of the hippocampal-prefrontal pathway on the cognitive deficits imposed by early-life seizures. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LOPES-AGUIAR, CLEITON; RUGGIERO, RAFAEL N.; ROSSIGNOLI, MATHEUS T.; ESTEVES, INGRID DE MIRANDA; PEIXOTO-SANTOS, JOSE EDUARDO; ROMCY-PEREIRA, RODRIGO N.; LEITE, JOAO P. Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo. SCIENTIFIC REPORTS, v. 10, n. 1 APR 28 2020. Web of Science Citations: 0.
BUENO-JUNIOR, LEZIO S.; PEIXOTO-SANTOS, JOSE E.; RUGGIERO, RAFAEL N.; AVILA, MILTON A. V.; MARQUES, DANILO B.; LOPES-AGUIAR, CLEITON; LEITE, JOAO P. Interaction between hippocampal-prefrontal plasticity and thalamic-prefrontal activity. SCIENTIFIC REPORTS, v. 8, JAN 22 2018. Web of Science Citations: 4.
ESTEVES, I. M.; LOPES-AGUIAR, C.; ROSSIGNOLI, M. T.; RUGGIERO, R. N.; BROGGINI, A. C. S.; BUENO-JUNIOR, L. S.; KANDRATAVICIUS, L.; MONTEIRO, M. R.; ROMCY-PEREIRA, R. N.; LEITE, J. P. CHRONIC NICOTINE ATTENUATES BEHAVIORAL AND SYNAPTIC PLASTICITY IMPAIRMENTS IN A STREPTOZOTOCIN MODEL OF ALZHEIMER'S DISEASE. Neuroscience, v. 353, p. 87-97, JUN 14 2017. Web of Science Citations: 6.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.