If released neurotransmitter molecules simply remained in the synaptic cleft, the postsynaptic membrane would become saturated and receptors would be constantly activated. The postsynaptic cell would remain hyperpolarized or depolarized and would be unresponsive additional APs arriving at the presynaptic cell. The more rapidly neurons can respond to input, the more information they can process in a given amount of time. Thus neurotransmitter must be cleared from the synaptic cleft shortly after it is released by the axon terminal.

Neurotransmitter action can be terminated in several ways. First, enzymes can destroy the neurotransmitter. Acetylcholine, for example, is rapidly destroyed by the enzyme acetylcholinesterase (AChE), which is present in the synaptic cleft in close association with ACh receptors on the postsynaptic membrane (see Figure 44.12). When AChE is inhibited, ACh lingers in the synaptic cleft, causing spastic (contracted) muscle paralysis and usually resulting in death. Some of the most deadly nerve gases developed for chemical warfare work by inhibiting AChE. Some agricultural insecticides, such as malathion, also inhibit AChE and can poison farm workers if used without safety precautions.

Neurotransmitter can also simply diffuse away from the cleft or be taken back up by the presynaptic membrane to be recycled. Glial cells also take up neurotransmitters. An antidepressant drug commonly prescribed under the brand name Prozac slows the reuptake of the neurotransmitter serotonin, thus enhancing serotonin’s activity at the synapse.