Serotonergic Regulation of Membrane Potential in Developing Rat Prefrontal Cortex: Coordinated Expression of 5-Hydroxytryptamine (5-HT)<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub>Receptors

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<jats:p>The developing prefrontal cortex receives a dense serotonergic innervation, yet little is known about the actions of serotonin [5-Hydroxytryptamine (5-HT)] in this region during development. Here, we examined the developmental regulation of 5-HT receptors controlling the excitability of pyramidal neurons of this region. Using whole-cell recordings in<jats:italic>in vitro</jats:italic>brain slices, we identified a dramatic shift in the effects of 5-HT on membrane potential during the postnatal developmental period. In slices derived from young animals [postnatal day (P) 6 to P19], administration of 5-HT elicits a robust depolarization of layer V pyramidal neurons, which gradually shifts to a hyperpolarization commencing during the third postnatal week. This progression is the result of coordinated changes in the function of 5-HT<jats:sub>7</jats:sub>and 5-HT<jats:sub>2A</jats:sub>receptors, which mediate different aspects of the depolarization, and of 5-HT<jats:sub>1A</jats:sub>receptors, which signal the late developing hyperpolarization. The loss of the 5-HT<jats:sub>7</jats:sub>receptor-mediated depolarization and the appearance of the 5-HT<jats:sub>1A</jats:sub>receptor-mediated hyperpolarization appears to reflect changes in receptor expression. In contrast, the decline in the 5-HT<jats:sub>2A</jats:sub>receptor depolarization with increasing age was associated with changes in the effectiveness with which these receptors could elicit a membrane depolarization, rather than loss of the receptors per se. Together, these results outline coordinated changes in the serotonergic regulation of cortical excitability at a time of extensive synaptic development and thus suggest a key role for these receptor subtypes in the postnatal development of the prefrontal cortex.</jats:p>

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