Much of our understanding of the functional role of the 5-HTT as a master modulator of the 5-HT system has been built upon work in rodents (98). As such, researchers have a ready platform and toolset from which to perform certain neural and molecular analyses in 5-HTT mutant rodents (e.g., in vivo measurement of brain 5-HT availability) that cannot be employed in humans. One of the key themes to emerge from this work is that the neural consequences of 5-HTT gene mutation extend well beyond the 5-HTT and its role as a regulator of 5-HT availability. 5-HTT null mutation leads to alterations throughout the 5-HT system that include changes in 5-HT receptor binding and 5-HT synthesis (56, 95). At the systems level, 5-HTT knockout mice exhibit an abnormally high density of excitatory dendritic spines on amygdala neurons and an increase in dendritic arborization of prefrontal cortex neurons (56). The implication here is that influence of 5-HTT variation may not be limited to effects on 5-HT availability or even on the 5-HT system. Recently, this implication was confirmed in a rhesus
