Spillover and synaptic cross talk mediated by glutamate and GABA in the mammalian brain

Abstract

Recently, the distinction between transmitters that use volume or wiring transmission has been blurred by several reports that both GABA and glutamate can act relatively remotely from their site of release. This chapter considers these evidence, and discusses the physiological and pathological roles of this form of signaling. The instances of extrasynaptic signalling, heterosynaptic interactions and cross talk listed above are not necessarily the most important phenomena mediated by amino acid spillover. Instead, they are the examples that have been observed with the available recording techniques. Indeed, the spatial arrangement of group I metabotropic receptors, just outside the edge of the synaptic cleft in many areas, would make them strong candidates for detecting glutamate spillover. However, it is more difficult to unravel activation of extra-synaptic receptors from conventional synaptic phenomena when the same post-synaptic cell detects both types of signal. Whether spillover-mediated transmission occurs extensively in the normal living brain is an open question; the anatomical evidence suggests that it is highly likely to occur at some synapses that are poorly isolated by glial processes. Because this phenomenon could severely impair the specificity of synaptic communication, it may be necessary to think of amino acid-mediated signaling as a mixture of volume and wiring transmission.