Functional implication of cerebral vascular networks in memory consolidation

décembre 2014 Directeur(s) de thèse : Nathalie MACREZ and Bruno BONTEMPI Résumé de thèse

While there is consensus that cerebral blood flow is distributed according to the metabolic demand of neurons, the contribution of vascular networks to memory consolidation, the process by which memories acquire stability over time, remains unknown. This process requires a transitory hippocampal-cortical interaction allowing the progressive remodeling of cortical neuronal networks supporting the remote memory trace.
By using a behavioral task requiring an associative olfactory memory coupled to cellular imaging techniques, we first reveal, in adult healthy rats, a functional dissociation between the reactivity and the architecture of cerebral vascular networks. We identify calcium signaling changes that occur in specific cerebral arteries, pointing to their ability to adapt their dynamics upon retrieval to enable the successful expression of either recent or remote memories. Moreover, we show that vascular networks undergo a time-dependent densification via an angiogenesis mechanism as early as one day after learning, including in cortical regions which will only support memory storage and retrieval weeks later. By specifically stimulating this early cortical angiogenesis, we were able to improve the performance of rats tested for remote memory.
Taken together, our results highlight the importance of vascular plasticity in modulating neuronal plasticity and cognitive functions. They also suggest that the early structural changes within vascular networks could constitute a permissive mechanism which regulates the development of cortical dendritic spines thought to support the progressive formation and storage of enduring memories.