Dual origins of functionally distinct O-LM interneurons revealed by differential 5-HT(3A)R expression
Nature Publishing Group
Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
Forebrain circuits rely upon a relatively small but remarkably diverse population of GABAergic interneurons to bind and entrain large principal cell assemblies for network synchronization and rhythmogenesis. Despite the high degree of heterogeneity across cortical interneurons, members of a given subtype typically exhibit homogeneous developmental origins, neuromodulatory response profiles, morphological characteristics, neurochemical signatures and electrical features. Here we report a surprising divergence among hippocampal oriens-lacunosum moleculare (O-LM) projecting interneurons that have hitherto been considered a homogeneous cell population. Combined immunocytochemical, anatomical and electrophysiological interrogation of Htr3a-GFP and Nkx2-1-cre:RCE mice revealed that O-LM cells parse into a caudal ganglionic eminence-derived subpopulation expressing 5-HT(3A) receptors (5-HT(3A)Rs) and a medial ganglionic eminence-derived subpopulation lacking 5-HT(3A)Rs. These two cohorts differentially participate in network oscillations, with 5-HT(3A)R-containing O-LM cell recruitment dictated by serotonergic tone. Thus, members of a seemingly uniform interneuron population can exhibit unique circuit functions and neuromodulatory properties dictated by disparate developmental origins.
This work was supported by an NICHD intramural award to C.J.M. We thank Daniel Abebe for expert technical assistance. We are grateful to Drs. Stuart Anderson (Uni. Pennsylvania) and Gord Fishell (NYU) for providing the Nkx2-1-cre and the RCE reporter mouse lines, respectively. The GENSAT BAC-Cre driver line (Htr3a-NO152) mice were obtained from Dr. Charles Gerfern (NIMH). We would also like to thank Dr. Ed Mann (Uni. Oxford, UK) for providing the code for the wavelet analyses.
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.
Vol. 16, pp. 1598 - 1607
PubMed Central ID
Place of publication