Cell and Tissue Research

, Volume 316, Issue 1, pp 99–113 | Cite as

Target areas innervated by PACAP-immunoreactive retinal ganglion cells

  • Jens HannibalEmail author
  • Jan Fahrenkrug
Regular Article


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.


Cholera toxin subunit B Suprachiasmatic nucleus Entrainment Circadian rhythm Melanopsin Rat (Wistar) 



Third ventricle


Anterior commissure


Anterodorsal thalamic nucleus


Anterior hypothalamic area


Anterior pretectal nucleus, dorsal part


Cholera toxin subunit B


Caudate putamen


Commissural pretectal nucleus


Dorsal geniculate nucleus


Intergeniculate leaflet


Lateral hypothalamic area


Lateral posterior thalamic nucleus


Lateral septum


Mammillary body


Medial preoptic nucleus


Medial pretectal nucleus


Optic chiasma


Olivary pretectal nucleus


Nucleus of the optic tract


Pituitary adenylate cyclase-activating polypeptide


PACAP receptor type 1


Periaqueductal gray


Periventricular hypothalamic nucleus


Posterior limitans thalamic nucleus


Posterior pretectal nucleus


Paraventricular thalamic nucleus


Paraventricular hypothalamic nucleus


Retinal ganglion cells


Retinohypothalamic tract


Suprachiasmatic nucleus


Superior colliculus


Substantia nigra, reticular part


Supraoptic nucleus


Subparaventricular zone


Ventral geniculate nucleus


Vasoactive intestinal peptide


VIP/PACAP receptor type 1


VIP/PACAP receptor type 2


Ventrolateral preoptic nucleus


Ventral tegmental area



The skillful technical assistance of Anita Hansen and Lea Charlotte Larsen is gratefully acknowledged.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of Clinical Biochemistry, Bispebjerg HospitalUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Clinical BiochemistryBispebjerg HospitalCopenhagen NVDenmark

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