In models where 5-HT is reduced but not entirely eliminated (Figure 1, Low 5-HT; Table 1, Pet-1−/−, TPH-R439H knockin) the model predicts that high affinity 5-HT1A receptors on interneurons are preferentially engaged compared to those on pyramidal cells, relieving GABA-mediated inhibition of pyramidal neurons in the anxiety circuit, resulting in over-activation by even mild stressors and an elevated anxiety phenotype (Holmes, 2008). Here, TPH1 is linked to Anxiety.