Transcript Shelley A. Tischkau, Stacey L. Krager

Chapter 14
Orchestration of the Circadian Clock
Network by the Suprachiasmatic
Nucleus
Shelley A. Tischkau, Stacey L.
Krager
Copyright © 2014 Elsevier Inc. All rights reserved.
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FIGURE 14.1 The core molecular clock. CLK–BMAL1 drives the expression of genes containing E-box promoter
elements. In the core loop, CLK–BMAL1 drives transcription of Pers and Crys, dependent upon the availability of
BMAL1. Per–Cry heterodimers feedback to inhibit CLK–BMAL1 activity. Per–Cry is phosphorylated and subsequently
degraded by the proteosome. An accessory loop regulates BMAL1. CLK–BMAL1 also drives production of Rev-erbα
and Rora, which have opposing effects on production of BMAL1. Finally, CLK–BMAL1 drives production of clock control
genes (ccgs).
Copyright © 2014 Elsevier Inc. All rights reserved.
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FIGURE 14.2 General structure of the heterogeneous SCN. SCN is divided into core and shell regions. The core
contains the primary oscillator, which drives oscillations in the shell. VIP, GABA, and others are projected as
neurotransmitters that provide coupling between core and shell. The core also receives the primary input, especially
from the RHT, via glutamate and PACAP release. Core neurons express VIP and GRP, as well as calbindin, calretinin,
and GABA. Shell neurons express AVP, angiotensin II, met-enkephalin, GABA, and somatostatin (SST).
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FIGURE 14.3 Afferent and efferent pathways associated with the SCN. A simplified version of the afferent and
efferent connections of the SCN is shown. Photic input (orange) arises from the RHT (glutamate and PACAP) directly
and from the GHT (GABA and NPY) indirectly. Nonphotic input (red) arrives from the DRN, indirectly from the IGL
(GABA and NPY) and directly from the MRN (serotonin an 5-HT). Output pathways are shown in blue. Primary outputs
are to the hypothalamus, via the subparaventricular zone (dSPV, mSPV), PVN, and DMH. Autonomic output arises from
the PVN connection in the dorsal motor nucleus of the vagus (DMV). The hypothalamic–pituitary axis is controlled
primarily via output from the PVN to the median eminence (ME). Melatonin is controlled via a multisynaptic pathway
from the PVN to the IML, SCG, and then the pineal.
Copyright © 2014 Elsevier Inc. All rights reserved.
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