Serotonin-2C and -2A Receptor Co-expression on Cells in the Rat Medial Prefrontal Cortex
C. Nocjar, Katherine D. Alex, Alex Sonneborn, Atheir I. Abbas, B. Roth, E. A. Pehek
Neuroscience March 27, 2015 DOI: 10.1016/j.neuroscience.2015.03.050 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Immunofluorescence with confocal microscopy (animal tissue histology) Peer reviewed |
|---|---|
| Population | Layers V-VI of the prelimbic medial prefrontal cortex (species not stated in the abstract) |
| Topics | Serotonin |
| Key points | Most GABAergic cells in the deep prelimbic mPFC expressed 5-HT2C receptor immunoreactivity, and most 5-HT2C-expressing cells notably co-expressed 5-HT2A receptors. About 27% of 5-HT2C-immunoreactive cells were not GABAergic, and some co-labeled cells had pyramidal shape, which the authors say indirectly indicates the two receptors may be commonly co-expressed on GABAergic cells and perhaps co-localized on a small population of pyramidal projection cells. |
Abstract
Neural function within the medial prefrontal cortex (mPFC) regulates normal cognition, attention and impulse control, implicating neuroregulatory abnormalities within this region in mental dysfunction related to schizophrenia, depression and drug abuse. Both serotonin -2A (5-HT2A) and -2C (5-HT2C) receptors are known to be important in neuropsychiatric drug action and are distributed throughout the mPFC. However, their interactive role in serotonergic cortical regulation is poorly understood. While the main signal transduction mechanism for both receptors is stimulation of phosphoinositide production, they can have opposite effects downstream. 5-HT2A versus 5-HT2C receptor activation oppositely regulates behavior and can oppositely affect neurochemical release within the mPFC. These distinct receptor effects could be caused by their differential cellular distribution within the cortex and/or other areas. It is known that both receptors are located on GABAergic and pyramidal cells within the mPFC, but it is not clear whether they are expressed on the same or different cells. The present work employed immunofluorescence with confocal microscopy to examine this in layers V-VI of the prelimbic mPFC. The majority of GABA cells in the deep prelimbic mPFC expressed 5-HT2C receptor immunoreactivity. Furthermore, most cells expressing 5-HT2C receptor immunoreactivity notably co-expressed 5-HT2A receptors. However, 27% of 5-HT2C receptor immunoreactive cells were not GABAergic, indicating that a population of prelimbic pyramidal projection cells could express the 5-HT2C receptor. Indeed, some cells with 5-HT2C and 5-HT2A receptor co-labeling had a pyramidal shape and were expressed in the typical layered fashion of pyramidal cells. This indirectly demonstrates that 5-HT2C and 5-HT2A receptors may be commonly co-expressed on GABAergic cells within the deep layers of the prelimbic mPFC and perhaps co-localized on a small population of local pyramidal projection cells. Thus a complex interplay of cortical 5-HT2A and 5-HT2C receptor mechanisms exists, which if altered, could modulate efferent brain systems implicated in mental illness.