Serotonergic regulation of NMDA receptor trafficking and function in prefrontal cortex

Serotonin is synthesized in brain stem raphe nuclei and has widespread projections in the brain. One of the major targets is prefrontal cortex (PFC), which is located anterior of the frontal lobe. PFC transmits information to and from multiple brain regions including cortex, thalamus, hypothalamus, brain stem, basal ganglia, and limbic areas. PFC contains two primary neuronal populations: glutamatergic pyramidal projection neurons (∼80%) and GABAergic interneurons (∼20%). Working memory, a form of on-line holding and mental manipulation of information, has been found to require the sustained activity of PFC neurons (Goldman-Rakic, 1995). Functional study in primate shows that serotonin enhances firing of some PFC neurons during the delay period of a delayed-response task, a behavioral test for working memory (Williams et al., 2002).