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Target areas innervated by PACAP-immunoreactive retinal ganglion cells

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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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Acknowledgements

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

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark

    Jens Hannibal & Jan Fahrenkrug

  2. Department of Clinical Biochemistry, Bispebjerg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark

    Jens Hannibal

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  1. Jens Hannibal
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  2. Jan Fahrenkrug
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Correspondence to Jens Hannibal.

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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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