Dynamics of the cerebral microvasculature during the course of memory consolidation in the rat: physiological and altered conditions induced by hypertension and hypergravity
Defended: Decembre 20, 2016
PhD supervisor: Jean Luc Morel PhD, CR CNRS – IMN – Team: Dynamics of neuronal and vascular networks underlying memory processing)
While the cerebral microvasculature is known to adapt its activity according to the metabolic demand of surrounding neurons, the functional contribution of vascular networks to memory consolidation, the process by which memory traces acquire stability over time, remains elusive.
By using an associative olfactory memory task in rats coupled to biochemical and imaging techniques, we investigated the dynamics of vascular changes during memory consolidation which requires a transitory interaction between the hippocampus and distributed cortical regions that ultimately support storage of enduring memories. We found that remote memory formation was associated, upon encoding, with a hypoxic signal that triggered transitory angiogenesis in specific cortical regions which support memory storage and retrieval only weeks later.
Manipulating early cortical angiogenesis (ECA) by selectively blocking or stimulating the angiopoietin-2 signalling pathway impaired or improved remote memory retrieval, respectively. Enhancing ECA in spontaneously hypertensive rats, which exhibit reduced angiopoietin-2 expression when cognitively challenged and are unable to properly stabilize and/or retrieve remotely acquired information, was efficient in rescuing the observed memory deficit, thus confirming the functional importance of ECA as a prerequisite for the formation of remote memories.
Hypergravity, known to impair vascular functions, failed to alter the organization of recent and remote memory. Altogether, our findings identify ECA as a crucial neurobiological process underlying the formation and stabilization of remote memory.
They highlight the importance of vascular plasticity in modulating cognitive functions and suggest that the early structural changes within vascular networks constitute a permissive mechanism for the regulation of neuronal plasticity within cortical networks which support the formation and storage of enduring memories.
Keywords: Angiogenesis – Arterial hypertension – Cerebral plasticity – Cerebral vascular network – Hypergravity – Memory consolidation – Rat – Retrieval
PU Bordeaux Président
GAUQUELIN-KOCH Guillemette CNES Invitée
C.R.CNRS Directeur de thèse