Deciphering the astrocytic contribution to learning and relearning

Author:

Squadrani LorenzoORCID,Wert-Carvajal CarlosORCID,Müller-Komorowska DanielORCID,Bohmbach KirstenORCID,Henneberger ChristianORCID,Verzelli PietroORCID,Tchumatchenko TatjanaORCID

Abstract

AbstractAstrocytes play a key role in the regulation of synaptic strength and are thought to orchestrate synaptic plasticity and memory. Yet, how specifically astrocytes and their neuroactive transmitters control learning and memory is currently an open question. Recent experiments have uncovered an astrocyte-mediated feedback loop in CA1 pyramidal neurons which is started by the release of endocannabinoids by active neurons and closed by astrocytic regulation of the D-serine levels at the dendrites. D-serine is a co-agonist for the NMDA receptor regulating the strength and direction of synaptic plasticity. Activity-dependent D-serine release mediated by astrocytes is therefore a candidate for mediating between long-term synaptic depression (LTD) and potentiation (LTP) during learning. Here, we show that the mathematical description of this astrocytic regulation is consistent with the classic Bienenstock Cooper Munro (BCM) model for synaptic plasticity, which postulated the existence of an activity-dependent LTP/LTD threshold. We show how the resulting mathematical framework can explain the experimentally observed behavioral effects of astrocytic cannabinoid receptor knock-out on mice during a place avoidance task and give rise to new testable predictions about the learning process advancing our understanding of the functional role of neuron-glia interaction in learning.

Publisher

Cold Spring Harbor Laboratory

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