Figure 1.

Early post-natal 5-HT-PFC circuitry in anxiety models. Shown are the components of the Raphe 5-HT-PFC circuit in animals during the early post-natal period with no, low, normal or high levels of 5-HT neurotransmission as indicated. Evidence from genetic mouse models (Table 1) supports the importance of alterations in early post-natal circuitry in generating the adult anxiety phenotype. 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. Although 5-HT neurons are shown projecting separately to glutamatergic or GABAergic PFC neurons to illustrate the different activities of these pathways, the same 5-HT neuron may innervate both cells with different efficiency synapses or varicosities (Bang et al., 2012). The presence of 5-HT1A (yellow), 5-HT2A (orange) and GABA-A receptors (red) is shown, as well as the response in the target neurons (clouds), stimulatory (+) or inhibitory (−). The effect of chronic stress to stimulate pyramidal output is also indicated. It is postulated that 5-HT1A-mediated inhibition in the early post-natal period and perhaps adult is greater in interneurons than pyramidal neurons and that increased pyramidal neuronal activity triggers the anxiety phenotype, especially during the early post-natal period.