The Suprachiasmatic Nucleus and the Circadian Timing System - Progress in Molecular Biology and Translational Science - page 11

3.2. Neurochemical organization
Neurochemical organization as discussed here refers to the presence of bio-
logical molecules involved in intercellular communication. This is a topic that
has grown increasingly complex over the past three decades and is very impor-
tant to understanding SCN function. Although Cajal 80, 133 definitively proved
that neurons are discontinuous elements with functional polarity and Ref. 142
introduced the word “synapse,” identification of synaptic transmitters devel-
oped slowly between the 1920s and the 1960s with acetylcholine and gluta-
mate as excitatory transmitters and GABA and glycine as inhibitory
transmitters. Approximately 66% of all brain neurons produce glutamate
and 33% GABA with acetylcholine produced by all motor neurons and small
populations of pontine and basal forebrain neurons. Glycine is primarily found
in spinal cord. The other groups of small molecule transmitters are the cate-
cholamines dopamine, found in the substantia nigra and ventral tegmental
area, posterior hypothalamus, the medial hypothalamus, olfactory bulb and
retina, and norepinephrine found in pontine cell groups ( Ref. 140 ) . Neurons
producing the indoleamine serotonin are found in brainstem raphe nuclei. 81 It
has been evident for a number of years from immunocytochemistry, or glu-
tamic acid decarboxylase in situ hybridization, that all SCN neurons in the spe-
cies studied contain GABA (Refs. 82, 83,84,141 ). GABA is colocalized in
SCN neurons with one or more neuroactive peptides (cf. Refs. 6,85,88 ,
for reviews). In the rat, eight peptides have been found in SCN neurons
by immunocytochemistry, totaling nearly the same number as GABA neurons
(Ref. 6 ;see Table 1.2 ). The postsynaptic effects of peptides are complex
(cf. Refs. 32,86,87 , for reviews). In general, colocalized peptides are released
from terminals concomitantly with small-molecule transmitters, interact with
receptors, and are metabolized by peptidases with postsynaptic effects similar
to the small-molecule transmitter, but more complex and prolonged.
3.3. SCN organization in the rat brain
The pattern of organization in which the SCN is comprised of two
subdivisions evident in Nissl and Golgi material is quite evident as well
in material prepared with antisera against a variety of peptides. The major
peptide phenotypes are AVP, VIP, GRP, and calretinin (CAR). Smaller
numbers of SCN neurons produce enkephalin (ENK), somatostatin
(SS), substance P (SP), and neurotensin (NT; Table 1.1 ). As we have pre-
viously noted most, if not all SCN, neurons produce the inhibitory small
molecule transmitter, GABA. The total number of neurons characterized
by peptide phenotype is 79% of the total number of SCN neurons