Ultrastructural Localization of Serotonin2A Receptors in the Middle Layers of the Rat Prelimbic Prefrontal Cortex

Cortical serotonin(2A) receptors are hypothesized to be involved in the pathology and treatment of schizophrenia. Light microscopic studies in the rat prefrontal cortex have localized serotonin(2A) receptors to the dendritic shafts of pyramidal and local circuit neurons. Electrophysiological studies have predicted that these receptors are also located on glutamate terminals, whereas neurochemical studies have hypothesized that they are located on dopamine terminals in this area. The present study sought to determine the ultrastructural localization of immunoperoxidase labeling for serotonin(2A) receptors in the middle layers of the prelimbic portion of the rat prefrontal cortex. Serotonin(2A) receptor immunoreactivity was observed in 325 identifiable structures. Of these, 73% were postsynaptic profiles that were composed of either dendritic shafts (58%) or dendritic spine heads and necks (42%). Twenty-four percent of the labeled profiles were presynaptic axons and varicosities; most of these had morphological features that were characteristic of monoamine axons: thin diameter, lack of myelination, occasional content of dense-cored vesicles, and infrequent formation of synapses in single sections. The remainder of the labeled profiles (4%) were glial processes. These findings suggest that serotonin(2A) receptor-mediated effects within the rat prelimbic prefrontal cortex are primarily postsynaptic in nature, affecting both the spines of pyramidal cells and the dendrites of pyramidal and local circuit neurons in this area. The results further suggest that serotonin acts presynaptically via this receptor subtype, most likely at receptors on monoamine fibers, and only rarely directly on glutamate axons.