title: Descending pathways from the paraventricular nucleus contribute to the recruitment of brainstem nuclei following a systemic immune challenge.
abstract: Hypothalamic nuclei, particularly the paraventricular nuclei (PVN), are important brain sites responsible for central nervous system responses during an immune challenge. The brainstem catecholamine cells of the nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM) have been shown to play critical roles in relaying systemic immune signals to the PVN. However, whilst it is well recognised that PVN divisions also innervate the NTS and VLM, it is not known whether descending PVN pathways can modulate the recruitment of brainstem cells during an immune challenge. Using systemic administration of the proinflammatory cytokine interleukin-1beta, in combination with Fos immunolabelling, we firstly investigated the effect of PVN lesions on NTS and VLM catecholamine and non-catecholamine cell responses. We found that ibotenic acid lesions of the PVN significantly reduced numbers of Fos-positive non-catecholamine, noradrenergic and adrenergic cells observable in the VLM and NTS after interleukin-1beta administration. We then investigated the origins of descending inputs to the VLM and NTS, activated by systemic interleukin-1beta, by mapping the distribution of Fos-positive retrogradely-labelled cells in divisions of the PVN after iontophoretically depositing choleratoxin-b subunit into the NTS or VLM one week prior to interleukin-1beta administration. We found that, after either NTS or VLM deposits, the majority of retrogradely-labelled Fos-positive cells activated by interleukin-1beta were localised in the medial and lateral parvocellular PVN divisions. Retrogradely-labelled Fos-positive cells were also observed in the NTS after VLM deposits, and in the VLM after NTS tracer deposits, suggesting reciprocal communication between these two nuclei after systemic interleukin-1beta. Thus the present study shows that the PVN has the capacity to modulate NTS and VLM responses after an immune challenge and that these may result from descending projections arising in the medial and lateral PVN divisions. These findings suggest that central nervous system responses to an immune challenge are likely to involve complex reciprocal connections between the PVN and the brainstem as well as between brainstem nuclei themselves.
authors.affiliation: Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Qld. 4072, Brisbane, Australia. k.buller@mailbox.uq.edu.au
authors.forename: K M
authors.initials: KM
authors.lastname: Buller
authors.forename: C V
authors.initials: CV
authors.lastname: Dayas
authors.forename: T A
authors.initials: TA
authors.lastname: Day
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002772:Cholera Toxin / Q000378:metabolism; D003714:Denervation; D004525:Efferent Pathways / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D015213:Neuroimmunomodulation / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012154:Reticular Formation / Q000502:physiology; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology
chemical_list: D002395:Catecholamines; D018836:Inflammation Mediators; D007375:Interleukin-1; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; D002772:Cholera Toxin