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Using a combination of anterograde and retrograde neuronal tract-tracing techniques, the descending projections from the paraventricular nucleus of the hypothalamus (PVN) to the brain/spinal cord and in particular those axonal projections that appear to be contiguous with sympathetic preganglionic neurones (SPN) projecting to the stellate ganglion have been studied. Descending PVN pathways were located by the anterograde transport of biotinylated dextran amine (BDA), whilst SPN were retrogradely labelled with cholera B toxin subunit conjugated to horseradish peroxidase (CB-HRP). BDA-labelled PVN axons terminated in both hypothalamic and extrahypothalamic (including the midbrain, medulla and spinal cord) brain nuclei, with dense terminal labelling observed particularly in the arcuate hypothalamic nucleus and adjacent median eminence, in the solitary tract, vagal nuclei and in the intermediolateral region of the spinal cord (IML). Varicose descending PVN fibres in the IML were often observed to closely appose both the cell soma and dendrites of retrogradely labelled SPN (projecting to the stellate ganglion) in the spinal cord. In addition, it was shown that PVN descending axons crossing to the contralateral side of the spinal cord were closely associated with retrogradely labelled SPN projecting to the superior cervical ganglion. Such findings suggest that descending pathways from the PVN may exhibit a direct influence on cardiac sympathetic outflow and may also influence the behaviour of the contralateral population of SPN projecting to the superior cervical ganglion.

1. The functional role of the paraventricular nucleus (PVN) has been examined by studying its connections with cardiovascular neurons in the medulla and spinal cord and its influence on activity in several sympathetic nerves. 2. Chemical stimulation of neurons within the PVN can elicit pressor responses and can excite reticulo-spinal vasomotor neurons in the rostral ventrolateral medulla (RVLM). 3. The PVN-RVLM excitation is blocked by kynurenic acid applied iontophoretically in the vicinity of RVLM-spinal neurons, suggesting this is a glutamate-dependent pathway. 4. Electrical stimulation of PVN neurons evoked action potentials in RVLM neurons after 27 ms with a small variability. 5. Anterograde and retrograde labelling of PVN and RVLM neurons revealed PVN terminals closely associated with RVLM-spinal neurons and showed that the PVN is connected to the spinal cord via three pathways. 6. Chemical activation of PVN neurons can produce a pattern of activation of cardiovascular neurons similar to that occurring in defence against plasma volume expansion. 7. It is concluded that the PVN connections with the RVLM and spinal cord are important to a role in defending against life-threatening disturbances.

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