Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons

Kenneth A Pelkey; Elizabeth Barksdale; Michael T Craig; Xiaoqing Yuan; Madhav Sukumaran; Geoffrey A Vargish; Robert M Mitchell; Megan S Wyeth; Ronald S Petralia; Ramesh Chittajallu; Rose-Marie Karlsson; Heather A Cameron; Yasunobu Murata; Matthew T Colonnese; Paul F Worley; Chris J McBain

doi:10.1016/j.neuron.2015.02.020

Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons

Neuron. 2015 Mar 18;85(6):1257-72. doi: 10.1016/j.neuron.2015.02.020. Epub 2015 Mar 5.

Authors

Kenneth A Pelkey¹, Elizabeth Barksdale², Michael T Craig², Xiaoqing Yuan², Madhav Sukumaran², Geoffrey A Vargish², Robert M Mitchell², Megan S Wyeth², Ronald S Petralia³, Ramesh Chittajallu², Rose-Marie Karlsson⁴, Heather A Cameron⁴, Yasunobu Murata⁵, Matthew T Colonnese⁵, Paul F Worley⁶, Chris J McBain²

Affiliations

¹ Program in Developmental Neuroscience, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD 20892, USA. Electronic address: pelkeyk2@mail.nih.gov.
² Program in Developmental Neuroscience, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD 20892, USA.
³ Advanced Imaging Core National Institute of Deafness and Other Communication Disorders, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD 20892, USA.
⁴ Section on Neuroplasticity, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, 35 Lincoln Drive, Bethesda, MD 20892, USA.
⁵ Department of Pharmacology and Physiology, and Institute for Neuroscience, George Washington University, 2300 Eye Street, Washington, DC 20037, USA.
⁶ The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, 725 N. Wolfe Street, Baltimore, MD 21205, USA.

Abstract

Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function. Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation with a prolonged critical period permissive for giant depolarizing potentials. Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition yielding a circuit deficient in rhythmogenesis and prone to epileptiform discharges. Our findings demonstrate an essential role for NPTXs in controlling network dynamics highlighting potential therapeutic targets for disorders with inhibition/excitation imbalances such as schizophrenia.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / physiology*
Animals
Animals, Newborn
C-Reactive Protein / deficiency
C-Reactive Protein / metabolism*
Disease Models, Animal
Interneurons / metabolism*
Mice
Mice, Knockout
Nerve Net / growth & development*
Nerve Tissue Proteins / deficiency
Nerve Tissue Proteins / metabolism*
Parvalbumins / metabolism*
Synapses / metabolism*

Substances

Nerve Tissue Proteins
Parvalbumins
neuronal pentraxin
C-Reactive Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding