Astrocytic Contributions to Long Term Memory & Synaptic Plasticity

Icahn School Of Medicine At Mount Sinai, New York NY

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Abstract

DESCRIPTION (provided by applicant): Memory consolidation is the process by which the newly learned information, which exists in a labile state, becomes a long-lasting memory that is resistant to disruption. Long-term memory consolidation requires de novo protein synthesis, and it is very likely that dendritic protein synthesis is also involved in this process. Long-term potentiation (LTP) is a persistent increase in synaptic strength, and is considered a cellular correlate for long-term memory. Like memory consolidation, late forms of LTP (L-LTP) also require protein synthesis, and have been shown to specifically require dendritic protein synthesis as well as somatic protein synthesis. Memories of emotional experiences such as those produced in the fear conditioning-based inhibitory avoidance (IA) paradigm, are subject to modulation by various hormones. Noradrenaline is released from the locus coeruleus during arousal and enhances memory via beta-adrenergic receptors. The same is true in regards to LTP, which is likewise modulated by noradrenaline. Recent evidence from our laboratory and others suggest that astrocytes play a larger role in both learning and memory and LTP than previously thought. By contributing lactate to neurons through glycogenolysis and transfer via monocarboxylate transporters, astrocytes are critical to memory consolidation and LTP maintenance (see preliminary data). Interestingly, beta-adrenergic receptors are present on astrocytes and have also metabolic effects in astrocytes when stimulated. This project will test the contribution of astrocytes to long-term memory and LTP. Specifically, it will test the hypothesis that astrocytes critically contribute to memory formation by providing astrocytic-neuronal coupling through lactate that supports the high-energy demands associated with activation of dendritic protein synthesis. Furthermore, it will test the hypothesis that the noradrenergic-dependent modulation of memory is mediated by the astrocytic-neuronal coupling.