Figure 1.

Model of 5-HT_1A autoreceptor effects on the serotonergic raphe nuclei. Schematic depicting representative raphe neurons in 1A-High and 1A-Low animals, emphasizing the differences between the two groups. (Top) In 1A-Low mice, low levels of somatodendritic 5-HT_1A autoreceptors result in weak negative feedback, resulting in higher firing rates of raphe neurons and concomitant increased release of serotonin. (Bottom) Conversely, 1A-High mice have lower basal firing rate and high levels of somatodendritic 5-HT_1A autoreceptor, which exert robust inhibitory effects on raphe firing. This results in a greater behavioral despair in response to stress, compared to 1A-Low mice. While 1A-High mice do not respond behaviorally to treatment with the antidepressant fluoxetine, 1A-Low mice display a robust behavioral response. 1A-High and 1A-Low mice provide a mechanistic model for humans carrying, respectively, the G/G and C/C alleles of the Htr1aI C(-1019)G polymorphism. Adapted from Richardson-Jones et al. 2010.