What defines a substance as a neurotransmitter?

  1. The substance must be present within the presynaptic neuron. A chemical cannot be secreted from a presynaptic neuron unless it is present there! Because elaborate biochemical pathways are requird to produced neurotransmitters, showing that the enzymes and precursors required to synthesize the substance are present in presynaptic neurons provides some evidence that the substance is used as a transmitter. (However, since the transmitters glutamate, glycine, and aspartate are also needed for protein synthesis and other metabolic reations in all neurons, their presence is not sufficient evidence to establish them as neurotransmitters.)
  2. The substance must be released in response to presynaptic depolarization, which must occur dependant on Ca2+. Another essential criterion for identifying a neurotransmitter is to demonstrate that it is released from the presynaptic neuron in response to presynaptic electrical activity, and that this release requires Ca2+ influx into the presynaptic terminal.
  3. Specific receptors for the substance must be present on the postsynaptic cell. A neurotransmitter cannot act on its target unless specific receptors for the transmitter are present in the postsynaptic membrane. One way to demonstrate receptors is to show that application of exogenous transmitter mimics the postsynaptic effect of presynaptic stimulation.

Neuroscience, Sinaur Associates (QP355.2.N487 1997)