title: Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network.
abstract: Hippocampal network activity is generated by a complex interplay between excitatory pyramidal cells and inhibitory interneurons. Although much is known about the molecular properties of excitatory synapses on pyramidal cells, comparatively little is known about excitatory synapses on interneurons. Here we show that conditional deletion of the postsynaptic cell adhesion molecule neuroligin-3 in parvalbumin interneurons causes a decrease in NMDA-receptor-mediated postsynaptic currents and an increase in presynaptic glutamate release probability by selectively impairing the inhibition of glutamate release by presynaptic Group III metabotropic glutamate receptors. As a result, the neuroligin-3 deletion altered network activity by reducing gamma oscillations and sharp wave ripples, changes associated with a decrease in extinction of contextual fear memories. These results demonstrate that neuroligin-3 specifies the properties of excitatory synapses on parvalbumin-containing interneurons by a retrograde trans-synaptic mechanism and suggest a molecular pathway whereby neuroligin-3 mutations contribute to neuropsychiatric disorders.
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jai S
authors.initials: JS
authors.lastname: Polepalli
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Hemmings
authors.initials: H
authors.lastname: Wu
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Goswami
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Casey H
authors.initials: CH
authors.lastname: Halpern
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California, USA.|Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008822:Mice, Transgenic; D009415:Nerve Net / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D018094:Receptors, Metabotropic Glutamate; C098004:neuroligin 3