Le couple BDNF/CaMK : un important régulateur de la plasticité synaptique dans l'hippocampe

Abstract

La rétention mnésique des informations suppose une réorganisation des circuits neuronaux appelée plasticité synaptique. La LTP (long term potentiation), un modèle expérimental de plasticité synaptique surtout étudié dans l’hippocampe, induit une augmentation durable de l’efficacité de la transmission synaptique entre des fibres afférentes et les neurones qu’elles innervent. L’élévation de la concentration de calcium déclenchée par la stimulation des récepteurs du glutamate et l’activation résultante d’une famille de sérine/thréonine-kinases multifonctionnelles appelées CaMK (calcium/calmodulin-dependent protein kinases) sont des conditions nécessaires à l’établissement de la LTP. La plasticité synaptique dans l’hippocampe est contrôlée en retour par le BDNF (brain-derived neurotrophic factor), notamment dans la région CA1. Sa synthèse paraît impliquer, elle aussi, la famille des CaMK (calcium/calmodulin-dependent protein kinases) selon un double processus : l’induction de la synthèse du BDNF par CaMK1 et CaMK4, et l’entretien par le facteur de l’activité de CaMK2, véritable «mémoire moléculaire ».

Synaptic plasticity appears to be one of key processes that underly higher brain fonctions, such as learning and memory. One of the most intensively studied models for synaptic plasticity is long term potentiation (LTP) in the hippocampus, where activation of afferent nerve fibers with high frequency stimulation results in a stable and long-lasting increase in the efficacy of synaptic transmission. However, despite the considerable effort invested in elucidating the enzymes and second messengers involved in LTP, relatively little is known about exact mechanisms that lead to this long-term synaptic remodeling. Recently, it has become apparent that a family of calcium/calmodulin dependent kinases (CaMK) plays a major role in controlling the induction and maintenance of LTP. Importantly also, increasing evidence shows that neurotrophins are involved in specific aspects of hippocampal plasticity. In particular, the increase in the synthesis of brain-derived neurotrophic factor (BDNF) appears to be secondary to activation of transcription factors CREB/ATF1 by CaMK1 and CaMK4. Vice versa, BDNF is implicated in activation of CaMK1 and CaMK4, and appears reasonably to be able to produce enduring changes in activity of CaMK2. These data are likely to be important to begin to understand how interaplay between CaMK and BDNF might consolidate information storage in hippocampus. [References: 42]