mGluR7 is a metaplastic switch controlling bidirectional plasticity of feedforward inhibition.
Plasticity of feedforward inhibition in the hippocampal mossy fiber (MF) pathway can dramatically influence dentate gyrus-CA3 dialog. Interestingly, MF inputs to CA3 stratum lucidum interneurons (SLINs) undergo long-term depression (LTD) following high-frequency stimulation (HFS), in contrast to MF-pyramid (PYR) synapses, where long-term potentiation (LTP) occurs. Furthermore, activity-induced potentiation of MF-SLIN transmission has not previously been observed. Here we report that metabotropic glutamate receptor subtype 7 (mGluR7) is a metaplastic switch at MF-SLIN synapses, whose activation and surface expression governs the direction of plasticity. In naive slices, mGluR7 activation during HFS generates MF-SLIN LTD, depressing presynaptic release through a PKC-dependent mechanism. Following agonist exposure, mGluR7 undergoes internalization, unmasking the ability of MF-SLIN synapses to undergo presynaptic potentiation in response to the same HFS that induces LTD in naive slices. Thus, selective mGluR7 targeting to MF terminals contacting SLINs and not PYRs provides cell target-specific plasticity and bidirectional control of feedforward inhibition.
Pelkey
Kenneth A
KA
Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health, and Human Development, National Institutes of Health, Building 35, Bethesda, Maryland 20892, USA. pelkeyk2@mail.nih.gov
Lavezzari
Gabriela
G
Racca
Claudia
C
Roche
Katherine W
KW
McBain
Chris J
CJ
D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D007395:Interneurons / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7