Fig. 12.

Schematic representation of the putative relationships between projection neurons in mPFC and DR 5-HT neurons. Descending excitatory afferents from the mPFC control the activity of 5-HT neurons directly, via NMDA and AMPA–KA receptors, and indirectly, via activation of local inhibitory (5-HT_1A and GABA_A) receptors. The stimulus-induced excitation of neurons receiving a direct input from the mPFC (either 5-HT or GABAergic) releases 5-HT or GABA, which inhibit other 5-HT neurons via 5-HT_1A or GABA_A receptors. The involvement of 5-HT_1A receptors in the mPFC-induced inhibitions of 5-HT neurons is supported by the decrease in the proportion of inhibitions in rats depleted of 5-HT (Table 1) and by the reversal of the inhibitions induced by 5-HT_1A receptor blockade with WAY-100635. Additionally, GABAergic inputs may also occur via a serotonergic control of GABA interneurons (Liu et al., 2000). The firing activity of 5-HT neurons and the release of 5-HT in midbrain and forebrain are dependent on the activation of 5-HT_1Aautoreceptors in the DR. However, the activation by 8-OH-DPAT of postsynaptic 5-HT_1A receptors on cortical pyramidal neurons also reduces 5-HT cell firing in the DR and 5-HT release in the DR and mPFC, likely through the inhibition of the activity of excitatory inputs from the mPFC to the DR. Thus, pyramidal 5-HT_1Areceptors in mPFC are a second population of 5-HT_1Areceptors controlling serotonergic activity.