The Suprachiasmatic Nucleus and the Circadian Timing System - Progress in Molecular Biology and Translational Science - page 20

5. CONCLUSIONS
The SCN is comprised of individual neuronal oscillators that are
coupled by neural connections to function as a pacemaker controlling a
series of effector systems including those regulating the rest-activity cycle,
core body temperature, autonomic nervous system, neuroendocrine func-
tion, and a psychomotor performance. 98 The SCN is made up of two ana-
tomical and functional subdivisions, core and shell. Core contains VIP þ and
GRP þ neurons; receives primary and secondary visual afferents and input
from the median raphe; and projects upon shell, contralateral core, and a
select set of effector areas. Shell contains populations of AVP þ and CAR þ
neurons; receives input from hypothalamus, basal forebrain, limbic cortical
areas, thalamus, and brainstem; and projects to a wider set of effector areas
than core. Information processing in the SCN involves four steps: (1) inte-
gration of visual and related entraining input in the core; (2) intrinsic con-
nections among core neurons, from core to shell neurons and among shell
neurons; (3) commissural projections from core to core and from shell to
shell; (4) integration in the shell of input from the core and from a wide
set of nonvisual inputs. The conclusion from in vitro data, both explant cul-
tures and cultures containing individual neurons, is that most, if not all, SCN
neurons are circadian oscillators. 98,123 If this is indeed true, the further con-
clusion is that the circadian information relayed from shell and core to effec-
tor regions must differ. That is, output from core is the circadian output of
core neurons modified primarily by photic entrainment influences (from
RHT, GHT, and PHT), whereas the output from shell reflects the circadian
output of shell neurons modified both by entraining stimuli from core and
nonvisual modulating inputs from a wide set of areas ( Fig. 1.7 ) . Thus, the
circadian signal from the SCN is likely to vary with respect to the subdivision
of origin. The complexity of the output signal is further enhanced by the
number and variety of neuroactive substances that have been advanced as
candidate transmitters/modulators. In addition, the output to the preoptic
and anterior hypothalamic areas, SPVZ, and tuberal hypothalamus is likely
to be further affected by overlapping direct retinal projections (Refs.
104,111,150 ). A further level of complexity is introduced by humoral
and behavioral events that are components of feedback input to the SCN.
At this point, a comment on experimental models and methods is nec-
essary. The criteria for selecting an experimental paradigm include utility in
approaching a variety of problems, ease of use, replication of data both
within and between laboratories, minimal expense, and wide acceptance