The 5-HT2A-dependent increase in spontaneous events was not observed in the presence of TTX suggesting that these receptors do not alter presynaptic release of glutamate. Whereas 5-HT or 5-HT2A agonists generate only small, subthreshold depolarizations in most PFC pyramidal neurons tested, approximately a third of large pyramidal neurons in layer V/VI were strongly depolarized by these treatments (Beique et al., 2007). This is consistent with data from in situ hybridization studies showing that approximately 50% of glutamatergic neurons in prelimbic PFC express 5-HT2A mRNA with 26% of layer VIa showing strong expression (Santana et al., 2004). These findings suggest that the 5-HT2A-dependent increase in spontaneous events recorded in PFC neurons is due to direct excitation of a small number of excitatory neurons that spreads throughout the PFC due to the strong recurrent connections among deep-layer pyramidal neurons.
