The transition from sleep to waking is associated with the abolition of spindle waves in thalamocortical neurons and the GABAergic cells of the thalamic reticular/perigeniculate nuclei. We tested the possibility that norepinephrine (NE) and serotonin (5-HT) may abolish spindle wave generation through an enhancement of the hyperpolarization-activated cation current I(h) in thalamocortical neurons. Local application of agents known to enhance I(h), including 5-HT, NE, the adenylyl cyclase activator, forskolin, and the β-adrenergic agonist, isoproterenol, to lamina A1 of the dorsal lateral geniculate nucleus resulted in an abolition of local spindle wave generation in thalamocortical neurons. The abolition of spindle waves was reversed by the local application of the I(h) channel blocker, cesium. These results suggest that NE and 5-HT may abolish the generation of spindle waves through the modulation of I(h) in thalamocortical neurons.
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