Cell and Tissue Research

, Volume 316, Issue 1, pp 99–113

Target areas innervated by PACAP-immunoreactive retinal ganglion cells

Regular Article

DOI: 10.1007/s00441-004-0858-x

Cite this article as:
Hannibal, J. & Fahrenkrug, J. Cell Tissue Res (2004) 316: 99. doi:10.1007/s00441-004-0858-x

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.

Keywords

Cholera toxin subunit BSuprachiasmatic nucleusEntrainmentCircadian rhythmMelanopsinRat (Wistar)

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

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