Lithium modulates the muscarinic facilitation of synaptic plasticity and theta-gamma coupling in the hippocampal-prefrontal pathway

Autor(es)

Ruggiero, Rafael N. ^[1] ; Rossignoli, Matheus T. ^[1] ; Lopes-Aguiar, Cleiton ^{[1, 2]} ; Leite, Joao P. ^[1] ; Bueno-Junior, Lezio S. ^[1] ; Romcy-Pereira, Rodrigo N. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, Nucleo Neurociencias, BR-31270901 Belo Horizonte, MG - Brazil

^[3] Univ Fed Rio Grande do Norte, Brain Inst, Ave Nascimento de Castro 2155, BR-59056450 Natal, RN - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 304, p. 90-101, JUN 2018.
• Citações Web of Science: 0

Resumo

Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating electrode in the intermediate hippocampal CA1. Either of two forms of synaptic plasticity, long-term potentiation (LTP) or depression (LTD), were induced during pilocarpine effects, which were monitored in real time through local field potentials. We found that lithium attenuates the muscarinic potentiation of cortical LIP (<20 min) but enhances the muscarinic potentiation of LTD maintenance (>80 min). Moreover, lithium treatment promoted significant cross-frequency coupling between CA1 theta (3-5 Hz) and mPFC low-gamma (30-55 Hz) oscillations. Interestingly, lithium by itself did not affect any of these measures. Thus, lithium pretreatment and muscarinic activation synergistically modulate the hippocampal-prefrontal connectivity. Because these alterations varied with time, oscillatory parameters, and type of synaptic plasticity, our study suggests that lithium influences prefrontal-related circuits through intricate dynamics, informing future experiments on mood disorders. (AU)

• Processo FAPESP: 08/57413-7 - Plasticidade sináptica no córtex pré-frontal induzida por estimulação do tálamo mediodorsal de ratos in vivo: efeitos da modulação colinérgica muscarínica e nicotínica
• Beneficiário: Lézio Soares Bueno Júnior
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/17882-4 - Epilepsias farmacorresistentes: desafios diagnósticos, estudo das comorbidades associadas e novas abordagens experimentais
• Beneficiário: João Pereira Leite
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 05/56447-7 - Pesquisa através de imagens por ressonância magnética de alto campo destinadas a estudos em humanos
• Beneficiário: João Pereira Leite
• Linha de fomento: Auxílio à Pesquisa - Programa CINAPCE - Temático
• Processo FAPESP: 09/54410-0 - Papel da plasticidade sináptica na via hipocampo - córtex pré-frontal medial de ratos em livre-movimento submetidos a modelos de psicose: implicações para o estudo de comorbidades psiquiátricas em modelos experimentais de epilepsia do lobo temporal
• Beneficiário: Cleiton Lopes Aguiar
• Linha de fomento: Bolsas no Brasil - Doutorado