Hippocampal-prefrontal synaptic plasticity in awake rats: effects of thalamic stimulation during natural sleep and implications for memory consolidation

• Grant number: 12/06123-4
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): September 01, 2012
• Effective date (End): August 31, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: João Pereira Leite
• Grantee: Lézio Soares Bueno Júnior
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 12/21387-8 - Multi-unit recording from the prefrontal cortex with optogenetic stimulation of the locus coeruleus: unveiling neural mechanisms under an attention task, BE.EP.PD

Abstract

The consolidation of explicit memories occurs in discrete steps, possibly based on the oscillatory activity underlying slow-wave sleep (SWS) and rapid-eye-movement sleep (REMS). The direct input from hippocampal CA1 to the medial prefrontal cortex (mPFC) is crucial for such consolidation, whose synaptic plasticity mechanisms may be controlled by the level of synchronization between mPFC and its main diencephalic counterpart: the thalamic mediodorsal nucleus (MD). It is not yet known whether hippocampal-prefrontal plasticity would react to experimental interference on thalamic activity patterns underlying the sleep stages. Thus, our aim is to investigate how CA1-mPFC synaptic plasticity, induced in awake rats, is affected by electrical disturbance of the MD-mPFC loop selectively during SWS, a state with high thalamocortical synchronization. For that, we will record electrophysiological responses in mPFC evoked by alternate pulses into CA1 and MD using the same subjects, in order to simultaneously monitor the synaptic function of the two convergent afferents throughout 5-h recording sessions. In such sessions, we will induce CA1-mPFC plasticity during the wake. Then, we will apply high-frequency stimulation (100 Hz) into MD during the ensuing SWS, in order to disturb mPFC endogenous delta waves (0.5-4.0 Hz). Lastly, the brains will be processed for immunoreaction of structural plasticity-related proteins. Our study may help clarify the hippocampal-prefrontal dynamics under SWS and REMS, augmenting understanding on the cognitive loss caused by dysfunctional sleep. Furthermore, we expect to contribute to a better understanding on the physiology underlying memory consolidation, whose relation with sleep is still controversial.

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)

BUENO-JUNIOR, LEZIO S.; LEITE, JOAO P. Input Convergence, Synaptic Plasticity and Functional Coupling Across Hippocampal-Prefrontal-Thalamic Circuits. FRONTIERS IN NEURAL CIRCUITS, v. 12, MAY 23 2018. Web of Science Citations: 2.

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.

BUENO-JUNIOR, LEZIO S.; RUGGIERO, RAFAEL N.; ROSSIGNOLI, MATHEUS T.; DEL BEL, ELAINE A.; LEITE, JOAO P.; UCHITEL, OSVALDO D. Acetazolamide potentiates the afferent drive to prefrontal cortex in vivo. PHYSIOLOGICAL REPORTS, v. 5, n. 1 JAN 2017. Web of Science Citations: 2.