Burst firing mediated by a low-threshold spike (LTS) is the hallmark of many thalamic neurons. However, postburst afterhyperpolarizations (AHPs) are relatively uncommon in thalamus. We now report data from patch-clamp recordings in rat brain slice preparations that reveal an LTS-induced slow AHP (sAHP) in thalamic paraventricular (PVT) and other midline neurons, but not in ventrobasal or reticular thalamic neurons. The LTS-induced sAHP lasts 8.9 +/- 0.4 s and has a novel pharmacology, with resistance to tetrodotoxin and cadmium and reduction by Ni(2+) or nominally zero extracellular calcium concentration, which also attenuate both the LTS and sAHP. The sAHP is inhibited by 10 mM intracellular EGTA or by equimolar replacement of extracellular Ca(2+) with Sr(2+), consistent with select activation of LVA T-type Ca(2+) channels and subsequent Ca(2+) influx. In control media, the sAHP reverses near E(K(+)), shifting to -78 mV in 10.1 mM [K(+)](o) and is reduced by Ba(2+) or tetraethylammonium. Although these data are consistent with opening of Ca(2+)-activated K(+) channels, this sAHP lacks sensitivity to specific Ca(2+)-activated K(+) channel blockers apamin, iberiotoxin, charybdotoxin, and UCL-2077. The LTS-induced sAHP is suppressed by a beta-adrenoceptor agonist isoproterenol, a serotonin 5-HT(7) receptor agonist 5-CT, a neuropeptide orexin-A, and by stimulation of the cAMP/protein kinase A pathway with 8-Br-cAMP and forskolin. The data suggest that PVT and certain midline thalamic neurons possess an LTS-induced sAHP that is pharmacologically distinct and may be important for information transfer in thalamic-limbic circuitry during states of attentiveness and motivation.