Synaptic Islands Defined by the Territory of a Single Astrocyte

TLDR

Astrocytes in the mammalian brain modulate neuronal function by synchronizing firing and coordinating synaptic networks, yet the structural basis of this remains poorly understood. The study aimed to investigate the structural basis of astrocyte‑mediated neuronal synchrony and synaptic coordination by examining the three‑dimensional relationships between cortical astrocytes and neurons. Using transgenic and viral labeling of astrocytes with enhanced green fluorescent protein, the authors performed three‑dimensional reconstructions from tissue sections or live animals in vivo. They found that cortical astrocytes occupy distinct, nonoverlapping territories, each enwrapping about four neuronal somata (up to eight) and contacting 300–600 dendrites, supporting a model of functional synaptic islands confined within individual astrocyte domains that are modulated by astroglial Ca²⁺ signaling and gliotransmission.

Abstract

In the mammalian brain, astrocytes modulate neuronal function, in part, by synchronizing neuronal firing and coordinating synaptic networks. Little, however, is known about how this is accomplished from a structural standpoint. To investigate the structural basis of astrocyte-mediated neuronal synchrony and synaptic coordination, the three-dimensional relationships between cortical astrocytes and neurons was investigated. Using a transgenic and viral approach to label astrocytes with enhanced green fluorescent protein, we performed a three-dimensional reconstruction of astrocytes from tissue sections or live animals <i>in vivo</i>. We found that cortical astrocytes occupy nonoverlapping territories similar to those described in the hippocampus. Using immunofluorescence labeling of neuronal somata, a single astrocyte enwraps on average four neuronal somata with an upper limit of eight. Single-neuron dye-fills allowed us to estimate that one astrocyte contacts 300–600 neuronal dendrites. Together with the recent findings showing that glial Ca²⁺ signaling is restricted to individual astrocytes <i>in vivo</i>, and that Ca²⁺ signaling leads to gliotransmission, we propose the concept of functional islands of synapses in which groups of synapses confined within the boundaries of an individual astrocyte are modulated by the gliotransmitter environment controlled by that astrocyte. Our description offers a new structurally based conceptual framework to evaluate functional data involving interactions between neurons and astrocytes in the mammalian brain.