Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 22, Issue 5, Pages 1120-1126Publisher
WILEY
DOI: 10.1111/j.1460-9568.2005.04307.x
Keywords
afterhyperpolarization; 5-HT2A receptors; 5-hydroxytryptamine; pyramidal cell; slow afterhyperpolarizing current
Categories
Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH043985, R29MH043985] Funding Source: NIH RePORTER
- NIMH NIH HHS [MH 43985] Funding Source: Medline
Ask authors/readers for more resources
In spite of a growing understanding of the actions of 5-hydroxytryptamine (5-HT) in the prefrontal cortex, the specific cellular mechanism used by 5-HT in this region remains poorly understood. Previous studies have shown that 5-HT inhibits the afterhyperpolarization that follows a burst of spikes in pyramidal neurons. In the present study, we have used whole cell recordings in rat and mouse brain slices to re-examine this phenomenon with special emphasis on identifying the 5-HT receptor subtypes mediating this effect. Layer V pyramidal neurons display complex afterhyperpolarizations that are mediated predominantly by calcium-activated potassium channels and involve two distinct currents known as medium afterhyperpolarizating current and slow afterhyperpolarizating current (I-sAHP). Administration of 5-HT reduced the current underlying these afterhyperpolarizations by selectively inhibiting I-sAHP. Pharmacological analysis of this response indicates that the main receptor responsible for this inhibition belongs to the 5-HT2A subtype. Thus, alpha-methyl-5-HT and 2,5-dimethoxy-4-bromoamphetamine (DOB) mimic the effect of 5-HT and the effect of these agonists is blocked by MDL 100 907. Similarly, administration of alpha-methyl-5-HT is without effect in slices derived from 5-HT2A receptor knockout mice. However, 5-HT2A receptor blockade only partially suppressed the ability of 5-HT to inhibit I-sAHP. This suggests the involvement of at least one more receptor subtype in this response. Consistent with this idea, administration of 5-carboxyamido-tryptamine, an agonist exhibiting no detectable affinity for 5-HT2A receptors, was also capable of suppressing I-sAHP. These results identify 5-HT2A receptors as being primarily involved in mediating the 5-HT-induced inhibition of I-sAHP in prefrontal cortex, while also recognizing a contribution by an additional 5-HT receptor subtype.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available