Suprachiasmatic nucleus: a central autonomic clock

Abstract

Circadian rhythms are daily changes in behavior and physiology produced by the suprachiasmatic nucleus (SCN) even in the absence of external stimuli 1 , although photic input from the retina to the SCN entrains these changes to a 24-hour cycle. The SCN modulates autonomic and neuroendocrine function to prepare for diurnal or nocturnal changes in behavior, but its precise connections to the autonomic nervous system are unknown. We used viral transneuronal labeling 2 to demonstrate extensive connections of the SCN with diverse types of sympathetic as well as parasympathetic motor systems. Double-virus transneuronal tracing showed connections of single SCN neurons to multiple autonomic systems. However, targets of SCN modulation seem limited to those that operate continuously under tonic, rather than phasic, control.To demonstrate that the SCN is connected to all the major sympathetic outflow systems via a multisynaptic pathway 3-5 , we first used an attenuated pig herpesvirus, the Bartha strain of pseudorabies virus (PRV), as a retrograde transneuronal tracer ( Fig. 1). In 4 separate experiments using 49 rats, the superior cervical ganglion, stellate ganglion, adrenal gland or celiac ganglion was injected with PRV. In the celiac experiments, the vagus was sectioned below the diaphragm before PRV injections to prevent labeling of the central vagal motor system. After five to eight days, the rats were anesthetized and perfused with fixative; their brains were subsequently processed for two-color immunohistochemistry to demonstrate PRV and arginine vasopressin (AVP) in single neurons 6 . PRV infection was seen first in the dorsomedial SCN region, generally within five to six days of injection, but only after seven days in the celiac ganglion experiments. About 20% of infected neurons were AVP positive ( Fig. 1). One day later, infection spread to the ventrolateral SCN. Control intravenous PRV injections with comparable viral dosage and postinjection times did not result in SCN labeling (n = 33). Overall, these results indicate that the SCN connects with extensive and diverse types of sympathetic motor systems.Second, SCN cytochemistry was studied to establish participation of specific neuronal phenotypes in circadian cardiosympathetic regulation. Each rat (n = 12), received a PRV injection into the stellate ganglion, the main sympathetic ganglion innervating the heart; 5 days later, its lateral cerebral ventricle was injected with 100 µg of colchicine in 10 µl of saline to enhance neuropeptide accumulation in central neurons for better immunohistochemical detection. One day later, each rat was perfused. Subsequently, brain sections through the SCN were immunostained for PRV and one of four neuropeptides, AVP, vasoactive intestinal polypeptide (VIP), somatostatin or gastrin releasing peptide (GRP). AVP neurons were labeled during the early stage of SCN infection. When the infection spread into the ventrolateral SCN, ∼3% of the VIP-, ∼10% of the somatostatinand ∼4% of the GRP-labeled neuronal populations were labeled. B...

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

“…Our finding of a circadian phase effect on early-phase insulin secretion could be mediated through the circadian system via numerous mechanisms. First, there are multisynaptic projections from the SCN to the pancreas (33,34). Second, pancreatic cells contain circadian clocks and their disruption, by knocking out circadian clock gene Brain and muscle Arnt-like protein-1 (BMAL1) specifically within the pancreas, results in decreased insulin secretion and impaired glucose tolerance (21,23).…”

Suprachiasmatic GABAergic Inputs to the Paraventricular Nucleus Control Plasma Glucose Concentrations in the Rat via Sympathetic Innervation of the Liver

“…Transneuronal labeling of PRV-Bartha is a well established technique (Ueyama et al, 1999;Buijs et al, 2003) based on the uptake of PRV particles by axon terminals of the neurons projecting to the infected organ, retrograde transport of the virus to the neuronal cell bodies, replication within the neurons, release at the site where the cell bodies or dendrites of the PRV filled neurons are synaptically contacted by axon terminals of other neurons, and subsequent uptake by these axon terminals with retrograde transport. Uptake, but not replication, by glial cells prevents diffusion of the virus to other neurons that do not contact infected neurons (Card, 2001).…”

“…HGP can be stimulated by increased glucagon release from the endocrine pancreas, increased activity of the sympathetic input to the liver, or decreased activity of the parasympathetic input to the liver (Shimazu, 1967;Nonogaki, 2000). We hypothesized that the SCN controls HGP via its projections to the autonomic motor neurons that are in control of either the liver or endocrine pancreas (Jansen et al, 1997;Ueyama et al, 1999;La Fleur et al, 2000;Buijs et al, 2001).…”

Differential control of peripheral circadian rhythms by suprachiasmatic-dependent neural signals

“…In addition, metabolites such as glucose may directly entrain peripheral oscillators or act indirectly to induce endocrine signals that regulate circadian rhythms of gene expression (6). On the other hand, the autonomic innervation of peripheral organs provides a potential pathway for entrainment (7)(8)(9). For example, SCN lesions that compromise catecholamine rhythms eliminate oscillations of clock gene expression in mouse liver (10).…”