equally astonished by today's cogent, nearly molecule-by-molecule explanation of just what was twitching in those frog legs.

CHEMICALS AS SIGNALS

Unlike electricity, the brain's chemical messengers, the neurotransmitters, are difficult to identify from first observations. The action of electricity could be confirmed or disproved by home-style tests; but the activity and nature of a chemical compound that may be involved in the brain's signaling system demand more rigorous examination. The compound must meet a half dozen specific criteria to be considered a neurotransmitter —as opposed to, say, a “second messenger” in the brain, which broadcasts signals within a cell rather than conveying a signal from one cell to another. (Distinctions such as this, which may seem overly fine at first, have a way of turning out later to be crucial for understanding new, otherwise inexplicable data.)

To be recognized as a neurotransmitter, a chemical compound must satisfy six conditions: It must be (1) synthesized in the neuron, (2) stored there, and (3) released in sufficient quantity to bring about some physical effect; (4) when administered experimentally, the compound must demonstrate the same effect that it brings about in living tissue; and (5) there must be receptor sites specific to this compound on the postsynaptic membrane, as well as (6) a means for shutting off its effect, either by causing its swift decomposition or by reuptake, absorbing it back into the cell. Of course, before any of these items on the checklist come into question, the compound must somehow be detectable in the human brain—not always an easy matter, in view of the minute quantities involved.

One of the first substances to pass all the tests was acetylcholine (ACh). Widespread throughout the central nervous system, ACh usually has an excitatory function, but it can also



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