FoundationalConceptsNeuroscience

Otto Loewi’s investigation of the parasympathetic neural connec-
tions with the heart via the vagus nerve. In addition to its signaling
actions in the autonomic nervous system and at the neuromuscular
junction, ACh is also a neurotransmitter in the brain. ACh receptors
of both types—ionotropic and metabotropic—are found in the brain.
Unlike glutamate and GABA, molecules that are released by billions of
neurons as neurotransmitters, acetylcholine is produced and released
by a relatively small number of neurons—perhaps a few hundred
thousand—clustered into several regions deep in the brain’s interior.
These cholinergic neurons, however, send highly branched axons
throughout large parts of the brain and thus affect hundreds of mil-
lions and perhaps billions of brain neurons (Fig. 7.2).
The molecular precursors to ACh are the molecules acetate (or
acetic acid) and choline (part of the head-group component of phos-
phatidylcholine membrane lipids), both of which are found in abun-
dance throughout the human body. However, only nerve cells that
use ACh as a neurotransmitter have the capacity to make ACh from
these ubiquitous precursors. The enzyme choline acetyltransferase
catalyzes the synthesis of ACh from acetate and choline, and the gene
coding for this enzyme is expressed (transcribed and translated) only
in cholinergic neurons.
Similarly, only cholinergic neurons express the gene to make
acetylcholinesterase, the enzyme responsible for the rapid cleavage
of ACh back to acetate and choline after its release at axon terminals.
ACh is removed from the synaptic cleft by rapid enzymatic degrada-
tion rather than by direct reuptake into the axon terminal (as is the
case for most other neurotransmitters).