Serotonergic Modulation of the Prefrontal Cortex: From Neurons to Brain Waves

Humans are remarkably proficient at some sophisticated and abstract tasks such as learning, memory and flexibility. These tasks depend on the prefrontal cortex, the cortical region most evolved in primates (Fuster, 2001; Miller & Cohen, 2001). The prefrontal cortex includes the most anterior structures of the frontal lobes, with some imprecise anatomical boundaries between different species of mammals. It has been defined across species according to its reciprocal anatomical connections with the mediodorsal nucleus of the thalamus (nucleus MD). The prefrontal cortex controls the activity of many subcortical structures via the excitatory axons of pyramidal neurons. These projection neurons forward the output signals of a complex cortical microcircuit composed of distinct types of excitatory pyramidal neurons and numerous types of inhibitory interneurons. It receives, along with the thalamus, dense innervation from many brain regions, including the serotonergic nuclei of the brainstem. During the last decade, research conducted by many laboratories has revealed that serotonin is a major modulator of prefrontal functions at the behavioral, neuronal and network levels. Its influences on cortical processing are implemented through multiple receptors expressed by pyramidal neurons as well as interneurons. These complex modulatory signals are altered in many psychiatric disorders such as schizophrenia and depression, where changes in receptor expression, neuron activity and brain waves have been observed. Furthermore, many psychiatric treatments -for instance, some antipsychotics and antidepressantstarget the serotonergic system and the prefrontal cortex. Thus, understanding the role of serotonergic neurotransmission in prefrontal cortex function is of major importance. Here we present a summary of our findings on the anatomy, neurophysiology and pharmacology of the serotonergic system in the medial prefrontal cortex of the rat.