Modulation of photic resetting in rats by lesions of projections to the suprachiasmatic nuclei expressing p75 neurotrophin receptor.
The suprachiasmatic nuclei of the hypothalamus (SCN) are the site of the master circadian clock in mammals. The SCN clock is mainly entrained by the light-dark cycle. Light information is conveyed from the retina to the SCN through direct, retinohypothalamic fibres. The SCN also receive other projections, like cholinergic fibres from basal forebrain. To test whether cholinergic afferents are involved in photic resetting, lesions of cholinergic projections were performed in rats with intracerebroventricular (i.c.v.) injections or intra-SCN microinjections of 192 IgG-saporin. When injected in the SCN, this immunotoxin destroys the cholinergic projections and retinohypothalamic afferents that express p75 low-affinity nerve growth factor (p75(NGF)) receptors. The extent of lesions in the basal forebrain and SCN was assessed by acetylcholinesterase histochemistry, p75(NGF) receptor, choline acetyl-transferase, calbindin-D28K and VIP immunocytochemistry. The intra-SCN treatment reduced light-induced phase advances by 30%, and induced a complete loss of forebrain and retinal afferents expressing p75(NGF) receptors within the SCN and a decrease of forebrain cholinergic neurons, most likely those projecting to the SCN. The i.c.v. treatment reduced light-induced phase advances by 40%, increased phase delays and led to extensive damage of forebrain p75(NGF)-expressing neurons, while sparing half of the fibres expressing p75(NGF) receptors (retinal afferents?) in the SCN. Because the integrity of forebrain p75(NGF)-expressing neurons appears to be critical in mediating the effects on light-induced phase advances, we therefore suggest that anterior cholinergic projections expressing p75(NGF) receptors modulate the sensitivity of the SCN clock to the phase advancing effects of light.
Erhardt
Christine
C
Laboratory of Neurobiology of Rhythms, Centre National de la Recherche Scientifique (UMR7518), Department of Neuroscience (IFR37), University Louis Pasteur, 12 rue de l'université, 67000 Strasbourg, France.
Galani
Rodrigue
R
Jeltsch
Hélène
H
Cassel
Jean-Christophe
JC
Klosen
Paul
P
Menet
Jérôme S
JS
Pévet
Paul
P
Challet
Etienne
E
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D001831:Body Temperature / Q000187:drug effects; D001927:Brain Diseases / Q000378:metabolism / Q000503:physiopathology; D064092:Calbindin 1; D064026:Calbindins; D002452:Cell Count / Q000379:methods; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D004333:Drug Administration Routes; D007150:Immunohistochemistry / Q000379:methods; D000922:Immunotoxins / Q000633:toxicity; D008027:Light; D008297:Male; D008474:Medial Forebrain Bundle; D009043:Motor Activity / Q000187:drug effects; D009699:N-Glycosyl Hydrolases; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism* / Q000528:radiation effects; D054789:Ribosome Inactivating Proteins, Type 1; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D000076985:Saporins; D013194:Staining and Labeling / Q000379:methods; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D000922:Immunotoxins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D064030:S100 Calcium Binding Protein G; D014660:Vasoactive Intestinal Peptide; D000110:Acetylcholinesterase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine