GABA release from suprachiasmatic nucleus terminals is necessary for the light-induced inhibition of nocturnal melatonin release in the rat.
The daily rhythm of melatonin production in the mammalian pineal is driven by the endogenous circadian pacemaker in the suprachiasmatic nuclei. The major release period of melatonin is closely linked to the dark phase of the 24-h day/night cycle. Environmental light will affect melatonin release in two ways: (i) it entrains the rhythm of the circadian oscillator; and (ii) it causes an acute suppression of nocturnal melatonin release. These two effects of light are both mediated by the suprachiasmatic nucleus and enable the pineal gland to convey information about day length to the reproductive system through changes in melatonin levels. Glutamate is currently believed to be the major transmitter in the retinal ganglion cell fibers reaching the suprachiasmatic nucleus. At present no information is available, however, about the transmitter(s) implicated in the further propagation, i.e. from the suprachiasmatic nucleus onwards, of the light information. In the present study we provide evidence that the endogenous release of GABA from suprachiasmatic nucleus terminals is implicated in the further transmission of light information to the pineal gland. Bilateral administration of the GABA-antagonist bicuculline to hypothalamic target areas of the suprachiasmatic nucleus completely prevents the inhibitory effect of nocturnal light on melatonin secretion and the present study thus documents that retina-mediated photic activation of suprachiasmatic nucleus neurons induces the release of GABA from efferent suprachiasmatic nucleus nerve terminals, resulting in an inhibition of melatonin release by the pineal gland. Together with our previous (electro)physiological data these results identify GABA as an important mediator of rapid synaptic transmission of suprachiasmatic nucleus output to its target areas.
Kalsbeek
A
A
Netherlands Institute for Brain Research, Amsterdam.
Cutrera
R A
RA
Van Heerikhuize
J J
JJ
Van Der Vliet
J
J
Buijs
R M
RM
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology* / Q000528:radiation effects; D003624:Darkness; D007839:Functional Laterality; D008027:Light; D008297:Male; D008550:Melatonin / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D008550:Melatonin; D001640:Bicuculline