Gating of retinal inputs through the suprachiasmatic nucleus: role of excitatory neurotransmission.
The mammalian circadian clock, located in the hypothalamic suprachiasmatic nucleus (SCN) is important in the regulation of many circadian rhythms, including regulation of pineal gland metabolism and melatonin secretion. Transsection of the optic nerves, disrupting the retinohypothalamic pathway, lesion of the SCN, or lesion of the hypothalamic paraventricular nucleus (PVN) abolish the regulation of pineal serotonin N-acetyltransferase activity by light. Therefore, the pathways linking the retina and the pineal gland must be channelled from the retina through the SCN and the PVN. Many lines of evidence indicate that the major neurotransmitter in the retinal afferents is glutamate. The first aim was therefore to study the retinal target neurons by localising glutamate receptors in the rodent SCN. Using in situ hybridisation, we detected NMDA-R1 and NMDA-R2C mRNA subunits in the SCN. Using immunocytochemistry, immunoreactivity for the AMPA type receptors GluR1, GluR2,3 and GluR4 was also detected in the SCN. Presentation of a short light pulse during the subjective night [i.e. circadian time (CT) 14 or 19], when light induced phase-shifting of activity-rest cycles can be accomplished, also induces expression of the immediate early-genes c-fos and junB in the rodent SCN. The second aim was to use this cellular correlate of behavioural function to determine the location of potential retinal target neurons in the SCN, and to investigate the hypothesis that glutamatergic neurotransmission mediates the effects of light on the circadian system. Thus, the ability of the NMDA receptor antagonist MK-801 to block light-induced c-fos expression in the SCN was studied. In the rat, this antagonist blocked c-fos mRNA expression in a subpopulation of cells in the ventral SCN at doses of 6, but not 2 mg/kg. In contrast, in the hamster both doses blocked light-induced c-fos expression in the ventral SCN. These data provide support for the hypothesis that glutamate mediates effects of light in the SCN, although it appers that the complexes of NMDA receptor subunits, which are involved in light-induced expression of c-fos after light, are relatively insensitive to MK-801. The diversity, heterogeneous distribution, and complexity of glutamate receptor subunits in the SCN suggest that processing of light pulses in the SCN is mediated by several cell types in the SCN. Via an integration process in the clock, the transmission of photic information takes place to other brain structures.
Mikkelsen
J D
JD
Institute of Medical Anatomy B, University of Copenhagen, Denmark.
Larsen
P J
PJ
Mick
G
G
Vrang
N
N
Ebling
F J
FJ
Maywood
E S
ES
Hastings
M H
MH
Møller
M
M
D000818:Animals; D002940:Circadian Rhythm; D006224:Cricetinae; D015870:Gene Expression; D017403:In Situ Hybridization; D008027:Light; D008297:Male; D008647:Mesocricetus; D009900:Optic Nerve / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D010870:Pineal Gland / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D012160:Retina / Q000502:physiology*; D015398:Signal Transduction; D013045:Species Specificity; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission; D013788:Thalamus / Q000502:physiology
D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate