A conceptual framework for astrocyte function

The participation of astrocytes in brain computation was hypothesized in 1992, coinciding with the discovery that these cells display a form of intracellular Ca2+ signaling sensitive to neuroactive molecules. This finding fostered conceptual leaps crystalized around the idea that astrocytes, once thought to be passive, participate actively in brain signaling and outputs. A multitude of disparate roles of astrocytes has since emerged, but their meaningful integration has been muddied by the lack of consensus and models of how we conceive the functional position of these cells in brain circuitry. In this Perspective, we propose an intuitive, data-driven and transferable conceptual framework we coin ‘contextual guidance’. It describes astrocytes as ‘contextual gates’ that shape neural circuitry in an adaptive, state-dependent fashion. This paradigm provides fresh perspectives on principles of astrocyte signaling and its relevance to brain function, which could spur new experimental avenues, including in computational space. Recent progress in astrocyte biology requires a more cohesive conceptual framework. This Perspective introduces a ‘contextual guidance’ paradigm in which astrocytes are key to adaptive modeling of neural circuits in response to state changes.