Elsevier

Brain Research

Volume 810, Issues 1–2, 9 November 1998, Pages 211-219
Brain Research

Research report
The source of origin of PACAP- and VIP-immunoreactive fibers in the laterodorsal division of the bed nucleus of the stria terminalis in the rat

https://doi.org/10.1016/S0006-8993(98)00692-1Get rights and content

Abstract

The bed nucleus of the stria terminalis (BSTL), which is known to be involved in the modulation of stress responses, exhibits a dense network of pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) immunoreactive (ir) fibers. The origin of the PACAP-ir fibers is unknown, and the origin of the VIP-ir fibers remains uncertain. The most important brain regions connected to the BSTL are the amygdaloid nuclei, the paraventricular and ventromedial hypothalamic nuclei, mesencephalic periaqueductal grey, the dorsal and linear raphe nuclei, the parabrachial nucleus, and the dorsal vagal complex. After microinjecting cholera toxin B subunit (CTB) in the BSTL as a retrograde tracer, neurons were double labeled for CTB and PACAP or VIP immunohistochemistry and the cells from which the PACAP- and VIP-ir fiber networks in the BSTL originated were identified. Cholera toxin B subunit labeled and VIP-ir cells were found in the mesencephalic periaqueductal grey and the dorsal and linear raphe nuclei, but no double labeled cells were seen in the amygdaloid nuclei or the hypothalamic region. CTB- and PACAP-ir neurons were observed in the paraventricular nucleus and the dorsal vagal complex. No double labeled perikarya were seen in the parabrachial nucleus or in the amygdaloid nuclei.

Introduction

The bed nucleus of the stria terminalis (BST) appears to be an important relay nucleus in the modulatory control of the hypothalamic and brainstem centers responsible for the behavioral, endocrinal, and physiological aspects of stress responses 16, 44, 49, 52. The BST is densely innervated by cholecystokinin immunoreactive (ir) [45], calcitonin gene-related peptide-ir 19, 47, catecholaminergic [33], neurotensin-ir, substance P-ir and enkephalin-ir [2]axon terminals. A dense pituitary adenylate cyclase activating polypeptide (PACAP) 25, 26, 27, 39and vasoactive intestinal polypeptide (VIP) 11, 27, 29, 43, 58immunoreactive fiber terminal network has also been described in the lateral division of the bed nucleus of the stria terminalis (BSTL). The distribution of corticotropin releasing factor-(CRF) [7], enkephalin- [58], GABA- 12, 34, galanin- 30, 48and dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive neurons [19]in the BSTL overlaps those of the PACAP- and VIP-ir fiber terminals. In addition, the concentration of PACAP in the human BSTL [37]and the concentrations of VIP and PACAP in the rat BSTL (unpublished RIA results of the authors) are the second highest in the brain. Several studies have shown VIP to be a neuromodulator and/or neurotransmitter 13, 50, 56. The excitatory action of PACAP on sympathetic preganglionic neurons [56]has been demonstrated, and it has been suggested that the peptide acts as a excitatory neuromodulator. Based on these data, we hypothesize a central role of PACAP- and VIP-ir axons in modulation of the physiological responses of BSTL neurons during stress.

The origin of PACAP-ir fibers to the BSTL is unknown. Many PACAP-ir neurons have been found in the amygdaloid nuclei [25], the paraventricular, supraoptic and periventricular hypothalamic nuclei 25, 39, and in the parabrachial nucleus [28], as well as in the nucleus of the solitary tract and the dorsal vagal nucleus (which form the so called dorsal vagal complex). Since all of these nuclei have anatomical connections with the BSTL, they are all possible sources of the PACAP-ir fiber terminals seen in the BSTL. The literature is inconsistent regarding the origin of the VIP-ir fiber terminals in the BSTL. Transection of the stria terminalis resulted in a marked loss of VIP-ir fiber terminals in the BSTL, indicating their amygdaloid origin 36, 42. Petit et al. [38], using a double immunohistochemical method, demonstrated that the dorsal and linear raphe nuclei were sources of the VIP-ir fiber terminals in the BSTL. The aim of the present study was to investigate the origin of the PACAP-ir and VIP-ir fiber terminals in the BSTL.

Section snippets

Animals

Twenty adult male CD rats (225–250 g; Charles River, Wilmington, MA, USA) were used in this study. All surgical procedures were conducted in accordance with NIH animal use guidelines and were approved by the Tulane University School of Medicine Advisory Committee for Animal Resources. The rats were deeply anesthetized with sodium pentobarbital (Nembutal, 45 mg/kg). Anesthesia was continued throughout the surgical procedures. After surgery the animals were housed individually under a 12 h light

Results

Injection of cholera toxin B subunit into the bed nucleus of the stria terminalis (Fig. 2A) resulted in retrogradely labeled perikarya in the central (Fig. 2B), cortical and basolateral amygdaloid nuclei (Fig. 1B), the periventricular, paraventricular and ventromedial hypothalamic nuclei (Fig. 1A), and in several mesencephalic nuclei (Fig. 1C and D), such as in the periaqueductal grey (Fig. 2E), dorsal and linear raphe nuclei, the parabrachial nucleus. In the dorsal vagal complex, which

Discussion

The results of previous studies on the source of origin of the VIP-ir fiber terminals in the BSTL are inconsistent 36, 38. Lesioning of the stria terminalis resulted in markedly decreased numbers of VIP-ir axon terminals in the BSTL, suggesting their amygdaloid origin. However, Petit et al. [38]eliminated this possibility and showed that mesencephalic structures such as the dorsal and linear raphe nuclei were the sources of origin of VIP-ir axon terminals in the BSTL. Our observation that the

Acknowledgements

The authors wish to thank to Mark Boone for his editorial assistance.

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