Glia as Active Participants in the Development and Function of Synapses

Long before the discovery of green fluorescent protein (GFP), Ramon y Cajal recognized glia’s intimate association with synapses in the brain. Though their function was at that time a mystery, he predicted that glia must be doing more than simply filling the spaces between neurons. Not surprisingly, Cajal was correct. Although incapable of firing action potentials, glia are highly excitable cells, communicating with neurons and other glia primarily through chemical signals. While it is well established that glia have many important support functions in the nervous system, emerging evidence reveals a far more dynamic role for glial cells at the synapse. We now appreciate that glia express many of the same voltage-gated ion channels and neurotransmitter receptors that neurons do and are thus well equipped to receive and transmit neuroactive signals. Through these mechanisms, glia can signal to pre and postsynaptic neurons and affect synaptic excitability and plasticity. Glia also actively communicate with one another in the form of calcium waves. The realization that dynamic bi-directional signaling between neurons and glia modulates synaptic transmission has led to re-definition of the synapse. The “tripartite synapse” is a term that was recently coined to incorporate glia as the third participant at the synapse, actively communicating with both the preand the post-synaptic neuron (2) (Fig. 1c). Glia also play an important role in the development and maintenance of synapses. Their appearance at synapses in the postnatal brain and developing neuromuscular junction coincides with periods of developmental plasticity. A growing body of research indicates a pivotal role for glial-derived signals in the formation of structural and functional synapses. In addition, glia appear to secrete multiple signals that control the remodeling and stabilization of synapses, as well as the modulation of synaptic plasticity. Glia as Active Participants in the Development and Function of Synapses