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.

Published in: Nature Neuroscience, A natureresearch journal

Autor(s):

Jai S Polepalli, Hemmings Wu, Debanjan Goswami, Casey H Halpern, Thomas C Südhof & Robert C Malenka

Publication Information:

Nature Neuroscience volume 20, pages 219–229 (2017)