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Neurohypophyseal Hormones: From Genomics and Physiology to Disease

Vasopressin induces depolarization and state-dependent firing patterns in rat thalamic paraventricular nucleus neurons in vitro

Neurosciences, Ottawa Health Research Institute and the University of Ottawa, Ottawa, Ontario, Canada

Submitted 1 November 2005 ; accepted in final form 2 December 2005

The thalamic midline paraventricular nucleus (PVT) is prominently innervated by vasopressin-immunoreactive neurons from the suprachiasmatic nucleus (SCN), site of the brain's biological clock. Using patch-clamp recordings in slice preparations taken from Wistar rats during the subjective day, we examined 90 PVT neurons for responses to bath-applied AVP (0.5–2 µM; 1–3 min). In current clamp at resting membrane potentials (–65 ± 1 mV), PVT neurons displayed low-threshold spikes (LTSs) and burst firing patterns. In 50% of cells tested, AVP induced a slowly rising, prolonged membrane depolarization and tonic firing, returning to burst firing upon recovery. AVP modulated hyperpolarization-activated LTSs by decreasing the time to the initial sodium spike at the onset of LTS, also increasing the duration of the afterdepolarization. Responses were blockable with a V_1a receptor antagonist (Manning compound). Under voltage clamp, AVP induced a TTX-resistant, slowly rising, and prolonged (15 min) inward current (<40 pA). Current-voltage relationship (I-V) analyses of the AVP responses revealed a decrease in membrane conductance to 73.1 ± 6.2% of control, with net AVP current reversing at –106 ± 4 mV, and decreased inward rectification at negative potentials. These observations are consistent with an AVP-induced closure of an inwardly rectifying potassium conductance. On the basis of these in vitro observations, we suggest that the SCN vasopressinergic innervation of PVT is excitatory in nature, possibly releasing AVP with circadian rhythmicity and contributing to state-dependent firing patterns in PVT neurons over the sleep-wake cycle.

suprachiasmatic nucleus; midline thalamus; neurohypophyseal peptide; circadian

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