When a neurotransmitter is released at a synapse, it reaches its highest concentration inside the narrow space of the synaptic cleft, but some of it is certain to diffuse away before being reabsorbed or broken down.  If it diffuses away, it has the potential to activate receptors that are located either at other synapses or on the membrane away from any synapse.  The extrasynaptic activity of a neurotransmitter is known as volume transmission.  It is well established that such effects occur to some degree, but their functional importance has long been a matter of controversy.
Recent work indicates that volume transmission may be the predominant mode of interaction for some special types of neurons.  In the mammalian cerebral cortex, a class of neurons called neurogliaform cells can inhibit other nearby cortical neurons by releasing the neurotransmitter GABA into the extracellular space. Along the same vein, GABA released from neurogliaform cells into the extracellular space also acts on surrounding astrocytes, assigning a role for volume transmission in the control of ionic and neurotransmitter homeostasis. Approximately 78% of neurogliaform cell boutons do not form classical synapses. This may be the first definitive example of neurons communicating chemically where classical synapses are not present.