  The participation of astrocytes in brain computation was formally
hypothesized in 1992, coinciding with the discovery that these glial cells
display a complex form of Ca2+ excitability. This fostered conceptual advances
centered on the notion of reciprocal interactions between neurons and
astrocytes, which permitted a critical leap forward in uncovering many roles of
astrocytes in brain circuits, and signaled the rise of a major new force in
neuroscience: that of glial biology. In the past decade, a multitude of
unconventional and disparate functions of astrocytes have been documented that
are not predicted by these canonical models and that are challenging to piece
together into a holistic and parsimonious picture. This highlights a disconnect
between the rapidly evolving field of astrocyte biology and the conceptual
frameworks guiding it, and emphasizes the need for a careful reconsideration of
how we theorize the functional position of astrocytes in brain circuitry. Here,
we propose a unifying, highly transferable, data-driven, and
computationally-relevant conceptual framework for astrocyte biology, which we
coin contextual guidance. It describes astrocytes as contextual gates that
decode multiple environmental factors to shape neural circuitry in an adaptive,
state-dependent fashion. This paradigm is organically inclusive of all
fundamental features of astrocytes, many of which have remained unaccounted for
in previous theories. We find that this new concept provides an intuitive and
powerful theoretical space to improve our understanding of brain function and
computational models thereof across scales because it depicts astrocytes as a
hub for circumstantial inputs into relevant specialized circuits that permits
adaptive behaviors at the network and organism level.
