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