Serotonin excites hippocampal CA1 GABAergic interneurons at the stratum radiatum-stratum lacunosum moleculare border

The hippocampus receives robust serotonergic innervation that is thought to control the excitability of both pyramidal cells and GABAergic interneurons. Previous work has addressed serotonergic regulation of pyramidal cells but considerable gaps remain in our understanding of how serotonin regulates different interneuron subclasses. 5-HT2A receptors (5-HT(2A)Rs) appear to localize predominantly, if not solely, on interneurons in the hippocampus and have been implicated in the regulation of hippocampal function including mnemonic and novelty recognition processes. Interneurons are functionally diverse. Therefore in the current work, we have used a BAC transgenic mouse line expressing EGFP under the control of the 5-HT2AR promoter to identify the interneuron subtype(s) regulated by serotonin via 5-HT(2A)Rs. We find that EGFP expression in this mouse identifies a group of interneurons that resides predominantly along the border of the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) of the CA1 region. We then show that these cells are depolarized and excited by serotonin acting through 5-HT(2A)Rs and appear to belong predominantly to the perforant pathway-associated and Schaffer collateral/commissural pathway-associated subtypes. These results indicate that serotonin interneurons expressing 5-HT(2A)Rs are localized primarily along the SR-SLM border of the CA1 region and represent a newly identified target for serotonin regulation in the hippocampus. (c) 2016 Wiley Periodicals, Inc.