Purinergic Signaling at Tripartite Synapses

Abstract

Astrocytes modulate synaptic transmission and plasticity via the release of gliotransmitters. ATP release by astrocytes and its chief metabolite, adenosine mediate astrocyte-neuron crosstalk through a plethora of ionotropic and metabotropic purinergic receptors and provide a unique framework that enables bidirectional modulation of neuronal excitability over a range of spatial and temporal scales. More recently dysregulation in purinergic signaling has also been associated with several disorders. The complexity of purinergic signaling and overlapping signaling pathways used by astrocytes and neurons makes it difficult to quantify the precise contribution of astrocytic release to function and yet provide a fertile ground for computational and modeling approaches. Here we review seminal experimental evidence on feedback and feedforward regulation of neuronal activity by astrocytes by means of purinergic signaling and pinpoint the essential requirements for a modeling framework to study this signaling at tripartite synapses. The ultimate goal would be to quantify the diverse functions of purinergic transmission stemming from a large variety of receptor type and spatiotemporal landscape.