Figure 2.

Adult 5-HT-PFC circuitry in depression models. Shown are the components of the Raphe 5-HT-PFC circuit in adult animals with no, low, normal or high levels of 5-HT neurotransmission as indicated. The model shows 5-HT neurons (orange) projecting to prefrontal cortex GABAergic interneurons (red) and glutamatergic pyramidal neurons (green) with transmitter release illustrated as small squares of the same colors. The presence of 5-HT1A (yellow), 5-HT2A (orange), AMPA-glutamate (green) and GABA-A receptors (red) is shown, as well as the response in the target neurons (clouds), stimulatory (+) or inhibitory (−). The effect of stress to stimulate pyramidal output is also indicated. It is postulated that 5-HT1A-mediated inhibition in adulthood becomes predominant in pyramidal neurons compared to interneurons, and that reduced activity of target pyramidal neurons elicits depression during adulthood.