Elsevier

Neuroscience

Volume 116, Issue 1, 15 January 2003, Pages 107-117
Neuroscience

Original contribution
Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex

https://doi.org/10.1016/S0306-4522(02)00580-8Get rights and content

Abstract

Cortical serotonin2A receptors are hypothesized to be involved in the pathology and treatment of schizophrenia. Light microscopic studies in the rat prefrontal cortex have localized serotonin2A 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 serotonin2A receptors in the middle layers of the prelimbic portion of the rat prefrontal cortex. Serotonin2A 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 serotonin2A 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.

Section snippets

Antibodies

Two 5-HT2AR antibodies were used in the present study. The first was a rabbit polyclonal antibody raised against amino acids 428–443 of the rat carboxyl-terminus. The specificity of this antibody has been previously characterized using immunoblots and immunocytochemistry (JB-124) (Backstrom and Sanders-Bush, 1997). The second was a commercially available mouse monoclonal antibody raised against amino acids 1–72 (PharMingen, San Diego, CA, USA) of the amino-terminus. The specificity was

Results

Within the middle layers of the rat PFC, immunoreactivity for 5-HT2ARs was moderately dense. The random sampling of tissue immunolabeled for the receptors revealed approximately 447 profiles. Of these, 325 could be readily identified. The remaining 122 did not contain sufficient organelles or other distinguishing characteristics in a single section to identify reliably the profile type. Therefore, only the clearly recognizable profiles will be discussed. The amount of tissue examined, the

Discussion

Using immunocytochemistry and electron microscopy, the present study established that in the rat prelimbic PFC, most 5-HT2ARs are located within postsynaptic structures, predominantly on proximal and distal dendritic shafts. This study also provides the first report of extensive localization of 5-HT2ARs to the heads and necks of dendritic spines. Presynaptically, 5-HT2ARs are present mainly in thin, unmyelinated axons and varicosities. These receptors are rarely observed in terminals forming

Conclusions

The present ultrastructural study suggests that the 5-HT2AR–mediated effects of serotonin within the middle layers of the rat PFC are predominantly postsynaptic in nature. Furthermore, the results imply that serotonin acts presynaptically through this receptor subtype, perhaps at receptors located on dopamine or other monoamine axons and varicosities. Conversely, our findings suggest that the 5-HT2AR–mediated effects of serotonin on the activity evoked by mediodorsal thalamic inputs to the

Acknowledgements

This work was supported by the following grants: MH50314 (S.R.S.), MH34007 (E.S.-B.) and National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (J.R.B.).

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