Glutamate and GABA spillover onto ionotropic and metabotropic receptors

The amino acid neurotransmitters glutamate and GABA are generally thought to subserve fast precise 'wiring' transmission at ionotropic receptors, and more diffuse spillover or 'volume' transmission at metabotropic receptors. However, within the hippocampal circuitry, glutamate and GABA can signal via spillover onto both metabotropic and lonotropic receptors. Moreover, glutamatergic axons can be affected by presynaptic GABA receptors, and GABAergic axons can be affected by presynaptic glutamate receptors. Finally, GABA tonically activates ionotropic; GABA receptors at subsets of neurons, and this phenomenon may play a homeostatic role in regulating GABA release. Although precise wiring signalling is preserved for very fast signals, on a slower timescale diffuse volume transmission has profound implications for the computational properties of the cortical microcircuitry.