Abstract
The vast diversity of GABAergic interneurons is believed to endow hippocampal microcircuits with the required flexibility for memory encoding and retrieval. However, dissection of the functional roles of defined interneuron types has been hampered by the lack of cell-specific tools. We identified a precise molecular marker for a population of hippocampal GABAergic interneurons known as oriens lacunosum-moleculare (OLM) cells. By combining transgenic mice and optogenetic tools, we found that OLM cells are important for gating the information flow in CA1, facilitating the transmission of intrahippocampal information (from CA3) while reducing the influence of extrahippocampal inputs (from the entorhinal cortex). Furthermore, we found that OLM cells were interconnected by gap junctions, received direct cholinergic inputs from subcortical afferents and accounted for the effect of nicotine on synaptic plasticity of the Schaffer collateral pathway. Our results suggest that acetylcholine acting through OLM cells can control the mnemonic processes executed by the hippocampus.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Animals
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Animals, Newborn
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CA1 Region, Hippocampal / cytology*
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CA3 Region, Hippocampal / cytology*
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Electric Stimulation
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / genetics
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GABA Antagonists / pharmacology
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Green Fluorescent Proteins
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In Vitro Techniques
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Interneurons / drug effects
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Interneurons / physiology*
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / genetics
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Nerve Net / physiology*
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Neurons / classification
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Neurons / physiology*
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Nicotine / pharmacology
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Nicotinic Agonists / pharmacology
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Patch-Clamp Techniques
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Picrotoxin / pharmacology
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Plant Lectins / genetics
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Plant Lectins / metabolism
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RNA, Messenger / metabolism
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Receptors, Nicotinic / genetics
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Valine / analogs & derivatives
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Valine / pharmacology
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Voltage-Sensitive Dye Imaging
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gamma-Aminobutyric Acid / metabolism
Substances
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CHRNA2 protein, human
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Luminescent Proteins
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Nicotinic Agonists
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Plant Lectins
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RNA, Messenger
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Receptors, Nicotinic
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tomato lectin
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Picrotoxin
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Green Fluorescent Proteins
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gamma-Aminobutyric Acid
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Nicotine
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-amino-5-phosphopentanoic acid
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Valine