Abstract
The retinohypothalamic tract (RHT) originates from a subset of retinal ganglion cells (RGCs). The cells of the RHT co-store the neurotransmitters PACAP and glutamate, which in a complex interplay mediate light information to the circadian clock located in the suprachiasmatic nuclei (SCN). These ganglion cells are intrinsically photosensitive probably due to expression of melanopsin, a putative photoreceptor involved in light entrainment. In the present study we examined PACAP-containing retinal projections to the brain using intravitreal injection of the anterograde tracer cholera toxin subunit B (ChB) and double immunostaining for PACAP and ChB. Our results show that the PACAP-containing nerve fibres not only constituted the major projections to the SCN and the intergeniculate leaflet of the thalamus but also had a large terminal field in the olivary pretectal nucleus. The contralateral projection dominated except for the SCN, which showed bilateral innervation. PACAP-containing retinal fibres were also found in the ventrolateral preoptic nucleus, the anterior and lateral hypothalamic area, the subparaventricular zone, the ventral part of the lateral geniculate nucleus and the nucleus of the optic tract. Retinal projections not previously described in the rat also contained PACAP. These new projections were found in the lateral posterior nucleus, the posterior limitans nucleus, the dorsal part of the anterior pretectal nucleus and the posterior and medial pretectal nuclei. Only a few PACAP-containing retinal fibres were found in the superior colliculus. Areas innervated by PACAP-immunoreactive fibres also expressed the PACAP-specific PAC1 receptor as shown by in situ hybridization histochemistry. The findings suggest that PACAP plays a role as neurotransmitter in non-imaging photoperception to target areas in the brain regulating circadian timing, masking, regulation of sleep-wake cycle and pupillary reflex.
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Abbreviations
- 3v :
-
Third ventricle
- ac :
-
Anterior commissure
- AD :
-
Anterodorsal thalamic nucleus
- AH :
-
Anterior hypothalamic area
- APTD :
-
Anterior pretectal nucleus, dorsal part
- ChB :
-
Cholera toxin subunit B
- CPu :
-
Caudate putamen
- CPT :
-
Commissural pretectal nucleus
- DGL :
-
Dorsal geniculate nucleus
- IGL :
-
Intergeniculate leaflet
- LH :
-
Lateral hypothalamic area
- LP :
-
Lateral posterior thalamic nucleus
- LS :
-
Lateral septum
- MB :
-
Mammillary body
- MPO :
-
Medial preoptic nucleus
- MPT :
-
Medial pretectal nucleus
- oc :
-
Optic chiasma
- OPT :
-
Olivary pretectal nucleus
- OT :
-
Nucleus of the optic tract
- PACAP :
-
Pituitary adenylate cyclase-activating polypeptide
- PAC1 :
-
PACAP receptor type 1
- PAG :
-
Periaqueductal gray
- Pe :
-
Periventricular hypothalamic nucleus
- PLi :
-
Posterior limitans thalamic nucleus
- PPT :
-
Posterior pretectal nucleus
- PVT :
-
Paraventricular thalamic nucleus
- PVN :
-
Paraventricular hypothalamic nucleus
- RGCs :
-
Retinal ganglion cells
- RHT :
-
Retinohypothalamic tract
- SCN :
-
Suprachiasmatic nucleus
- SC :
-
Superior colliculus
- SNR :
-
Substantia nigra, reticular part
- SON :
-
Supraoptic nucleus
- SPVZ :
-
Subparaventricular zone
- VGL :
-
Ventral geniculate nucleus
- VIP :
-
Vasoactive intestinal peptide
- VPAC1 :
-
VIP/PACAP receptor type 1
- VPAC2 :
-
VIP/PACAP receptor type 2
- VLPO :
-
Ventrolateral preoptic nucleus
- VTA :
-
Ventral tegmental area
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The skillful technical assistance of Anita Hansen and Lea Charlotte Larsen is gratefully acknowledged.
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This study was supported by The Danish Biotechnology Center for Cellular Communication and The Danish Neuroscience Programme. J.H. is postdoc funded by the Danish Medical Research Council (Jr. No. 0001716)
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Hannibal, J., Fahrenkrug, J. Target areas innervated by PACAP-immunoreactive retinal ganglion cells. Cell Tissue Res 316, 99–113 (2004). https://doi.org/10.1007/s00441-004-0858-x
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DOI: https://doi.org/10.1007/s00441-004-0858-x