Title: Ca 2+ -dependent and Na

18 Thalamic paraventricular nucleus (PVT) neurons exhibit a post-burst apamin-resistant 19 slow afterhyperpolarization (sAHP) that is unique to midline thalamus, displays activity 20 dependence and is abolished in tetrodotoxin. Analysis of the underlying sIAHP confirmed a 21 requirement for Ca influx with contributions from P/Q-, N-, Land R subtype channels, a 22 reversal potential near EK and a significant reduction by UCL-2077, barium or TEA, consistent 23 with a role for KCa channels. sIAHP was significantly reduced by activation of either the cAMP or 24 the PKC signaling pathway. Further analysis of the sAHP revealed an activity-dependent but 25 Ca-independent component that was reduced in high [K]o and blockable after Na substitution 26 with Li, or in the presence of quinidine, suggesting a role for KNa channels. The Ca27 independent sAHP component was selectively reduced by activation of the PKC signaling 28 pathway. The sAHP contributed to spike frequency adaptation which was sensitive to activation 29 of either cAMP or PKC signaling pathways and, near the peak of membrane hyperpolarization, 30 was sufficient to cause de-inactivation of low threshold T-Type Ca channels, thus promoting 31 burst firing. PVT neurons are densely innervated by orexin-immunoreactive fibers, and 32 depolarized by exogenously applied orexins. We now report that orexin A significantly reduced 33 both Ca-dependent and Ca-independent sIAHP, and spike frequency adaptation. Furthermore 34 orexin A-induced sIAHP inhibition was mediated through activation of PKC but not PKA. 35 Collectively, these observations suggest that KCa and KNa channels have a role in a sAHP that 36 contributes to spike frequency adaptation and neuronal excitability in PVT neurons, and that the 37 sAHP is a novel target for modulation by the arousaland feeding-promoting orexin 38 neuropeptides. 39