Abstract
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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Action Potentials / genetics
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Action Potentials / physiology
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Age Factors
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Animals
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Animals, Newborn
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Movement / genetics
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Cholecystokinin / metabolism
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Embryo, Mammalian
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Female
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology*
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Hippocampus / cytology*
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Hippocampus / physiology*
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In Vitro Techniques
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Interneurons / drug effects
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Interneurons / metabolism*
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Lysine / analogs & derivatives
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Lysine / metabolism
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Male
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Mice
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Mice, Transgenic
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Neural Pathways / drug effects
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Neural Pathways / metabolism
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Neurotransmitter Agents / pharmacology
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Nuclear Proteins / genetics
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Receptors, Serotonin, 5-HT3 / genetics
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Receptors, Serotonin, 5-HT3 / metabolism*
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Somatostatin / metabolism
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Thyroid Nuclear Factor 1
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Transcription Factors / genetics
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Vasoactive Intestinal Peptide / metabolism
Substances
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Ascl1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Luminescent Proteins
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Neurotransmitter Agents
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Nkx2-1 protein, mouse
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Nuclear Proteins
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Receptors, Serotonin, 5-HT3
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Thyroid Nuclear Factor 1
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Transcription Factors
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Vasoactive Intestinal Peptide
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Somatostatin
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Cholecystokinin
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biocytin
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Lysine