The authors have described a subregion of the hamster hypothalamic suprachiasmatic nucleus (SCN) containing cells that are immunopositive for the cytosolic calcium-binding protein, Calbindin-D 28K (CaBP). Several lines of evidence indicate that this region may constitute the site of the pacemaker cells that are responsible for the regulation of circadian locomotor rhythms. First, 79% of the CaBP-immunoreactive (ir) neurons express Fos in response to photic stimulation, indicating that they are close to or part of the input pathway to pacemakers. Second, at the light microscopy level, retinal terminals innervate the CaBP subnucleus. Finally, destruction of this subnucleus renders animals arrhythmic in locomotor activity. In this study, the authors examined the ultrastructural relationship between cholera toxin (CTÎČ) labeled retinal fibers and the CaBP-ir subregion within the hamster SCN. CTÎČ-ir retinal terminals make primarily axo-somatic, symmetric, synaptic contacts with CaBP-ir perikarya. In addition, retinal terminals form synapses with CaBP processes as well as with unidentified profiles. There are also complex interactions between retinal terminals, CaBP perikarya, and unidentified profiles. Given that axo-somatic synaptic input has a more potent influence on a cell's electrical activity than does axo-dendritic synaptic input, cells of the CaBP subregion of the SCN are ideally suited to respond rapidly to photic stimulation to reset circadian pacemakers.Keywords calcium-binding proteins; calbindin-D 28K ; CaBP; pacemaker; suprachiasmatic nucleus; retinal terminals; electron microscopy; circadian rhythmsThe suprachiasmatic nucleus (SCN) of the hypothalamus is the site of the putative circadian clock in mammals (see Klein et al., 1991). The circadian system regulates the periodicity of many rhythmic responses in mammals including rest-wake cycles (see Moore-Ede et al., 1982), electrical activity, and neuropeptide levels (Inouye, 1996), to name a few. In the absence of exogenous stimuli, the circadian clock oscillates with a periodicity that is close to 24 h. The circadian timing system also has the capacity to entrain or synchronize the organism to the exogenous geo-solar cycle. The primary neural substrate responsible for the © 2000 Sage Publications, Inc.Correspondence to: Maria-Teresa Romero. transduction of exogenous photic stimuli is the retinohypothalamic tract (RHT), a monosynaptic pathway projecting from the retina to the SCN (Card and Moore, 1991;Moore, 1996). A secondary pathway, the geniculo-hypothalamic tract, also provides photic input to the circadian pacemaker. Photic information is integrated in the SCN to produce a stable phase relationship between physiological and behavioral activity and the environmental light-dark cycle (Meijer, 1991). While it is clear that the SCN is the site of the circadian pacemaker, the precise identity of retinorecipient cells that mediate entrainment remains to be elucidated.
NIH Public AccessWe recently described cells immunopositive for Calbindin-D 28K (...