RESUMO
Evidence suggests that the acquisition of recognition memory depends upon CREB-dependent long-lasting changes in synaptic plasticity in the perirhinal cortex.The CREB-responsive microRNA miR-132 has been shown to regulate synaptic transmission and we set out to investigate a role for this microRNA in recognition memory and its underlying plasticity mechanisms. To this end we mediated the specific overexpression of miR-132 selectively in the rat perirhinal cortex and demonstrated impairment in short-term recognition memory. This functional deficit was associated with a reduction in both long-term depression and long-term potentiation. These results confirm that microRNAs are key coordinators of the intracellular pathways that mediate experience-dependent changes in the brain. In addition, these results demonstrate a role for miR-132 in the neuronal mechanisms underlying the formation of short-term recognition memory.
Assuntos
Córtex Cerebral/fisiologia , Regulação da Expressão Gênica , Potenciação de Longa Duração/genética , Memória de Curto Prazo/fisiologia , MicroRNAs/metabolismo , Reconhecimento Psicológico/fisiologia , Animais , Córtex Cerebral/metabolismo , Potenciais Pós-Sinápticos Excitadores , Células HeLa , Humanos , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Masculino , MicroRNAs/genética , Ratos , Ratos WistarRESUMO
The role of the CAMKK pathway in object recognition memory was investigated. Rats' performance in a preferential object recognition test was examined after local infusion into the perirhinal cortex of the CAMKK inhibitor STO-609. STO-609 infused either before or immediately after acquisition impaired memory tested after a 24 h but not a 20-min delay. Memory was not impaired when STO-609 was infused 20 min after acquisition. The expression of a downstream reaction product of CAMKK was measured by immunohistochemical staining for phospho-CAMKI(Thr177) at 10, 40, 70, and 100 min following the viewing of novel and familiar images of objects. Processing familiar images resulted in more pCAMKI stained neurons in the perirhinal cortex than processing novel images at the 10- and 40-min delays. Prior infusion of STO-609 caused a reduction in pCAMKI stained neurons in response to viewing either novel or familiar images, consistent with its role as an inhibitor of CAMKK. The results establish that the CAMKK pathway within the perirhinal cortex is important for the consolidation of object recognition memory. The activation of pCAMKI after acquisition is earlier than previously reported for pCAMKII.
