Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex.
Jean-Claude Béïque, Mays Imad, Ljiljana Mladenovic, Jay A Gingrich, Rodrigo Andrade
Proceedings of the National Academy of Sciences of the United States of America June 5, 2007 DOI: 10.1073/pnas.0700436104 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Cellular and molecular preparations (likely rodent cortex) |
| Key findings | Argues that 5-HT2A receptor activation facilitates intrinsic networks within the prefrontal cortex rather than eliciting retrograde messenger release or activating thalamocortical afferents, and identifies a discrete subpopulation of pyramidal cells strongly excited by this activation. |
Abstract
Classic hallucinogens such as lysergic acid diethylamide are thought to elicit their psychotropic actions via serotonin receptors of the 5-hydroxytryptamine 2A subtype (5-HT(2A)R). One likely site for these effects is the prefrontal cortex (PFC). Previous studies have shown that activation of 5-HT(2A)Rs in this region results in a robust increase in spontaneous glutamatergic synaptic activity, and these results have led to the widely held idea that hallucinogens elicit their effect by modulating synaptic transmission within the PFC. Here, we combine cellular and molecular biological approaches, including single-cell 5-HT(2A)Rs inactivation and 5-HT(2A)R rescue over a 5-HT(2A)R knockout genetic background, to distinguish between competing hypotheses accounting for these effects. The results from these experiments do not support the idea that 5-HT(2A)Rs elicit the release of an excitatory retrograde messenger nor that they activate thalamocortical afferents, the two dominant hypotheses. Rather, they suggest that 5-HT(2A)Rs facilitate intrinsic networks within the PFC. Consistent with this idea, we locate a discrete subpopulation of pyramidal cells that is strongly excited by 5-HT(2A)R activation.