Serotonergic projections are widespread in the developing neocortex, but their functions are obscure. The effects of 5-HT 3 receptor agonists on cortical circuit response properties were studied in slices of ferret primary visual cortex using high-speed optical imaging of voltage-sensitive dye signals and whole-cell patch-clamp recording. Activation of the 5-HT 3 receptor decreased the amplitude and lateral extent of excitation throughout postnatal development. This effect peaks after eye opening, which indicates a function for serotonergic modulation of circuit responses during the period of refinement of cortical connections. Whole-cell patch-clamp recordings from single neurons revealed that synaptic responses evoked by white matter stimulation were reduced by 5-HT 3 receptor agonists, whereas the During the developmental period before the onset of sensory function, intrinsically generated spontaneous activity is crucial to the differentiation of neocortical circuitry (for review, see Goodman and Shatz, 1993; Katz and Shatz, 1996). In the visual system this activity may originate in the retina (Feller et al., 1996; Weliky and Katz, 1997), the lateral geniculate nucleus, and/or the cortex itself (Ruthazer and Stryker, 1996). Intracortical synaptic activity may also be regulated by inputs from brain regions outside the primary visual pathway. Neuromodulatory brainstem afferents innervate the mammalian neocortex very early during development (DeLima an
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