Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons. 2015

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

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.

UI MeSH Term Description Entries
D007395 Interneurons Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions. Intercalated Neurons,Intercalated Neuron,Interneuron,Neuron, Intercalated,Neurons, Intercalated
D009415 Nerve Net A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction. Neural Networks (Anatomic),Nerve Nets,Net, Nerve,Nets, Nerve,Network, Neural (Anatomic),Networks, Neural (Anatomic),Neural Network (Anatomic)
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D010320 Parvalbumins Low molecular weight, calcium binding muscle proteins. Their physiological function is possibly related to the contractile process. Parvalbumin,Parvalbumin B
D002097 C-Reactive Protein A plasma protein that circulates in increased amounts during inflammation and after tissue damage. C-Reactive Protein measured by more sensitive methods often for coronary heart disease risk assessment is referred to as High Sensitivity C-Reactive Protein (hs-CRP). High Sensitivity C-Reactive Protein,hs-CRP,hsCRP,C Reactive Protein,High Sensitivity C Reactive Protein
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse

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