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Neto auxiliary proteins regulate NMDA receptor subunits at mossy fiber synapses onto CA3 pyramidal spines

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • MS Wyeth
  • KA Pelkey
  • RS Petralia
  • MW Salter
  • RR McInnes
  • CJ McBain


Neto1 and Neto2 proteins are auxiliary subunits of kainate receptors, conferring proper function and synaptic trafficking. Neto1 has also been implicated in regulating postsynaptic NMDA receptors at select synapses in the hippocampus. However, at mossy fiber synapses onto CA3 pyramidal cells, where Neto1 is strongly expressed, NMDA receptor-mediated currents are comparable between wildtype and Neto1/Neto2 knockouts. The present study further probed the mossy fiber synapse for potential changes in the underlying NMDA receptor subunits in Neto knockout mice. Postembedding electron microscopy labeled synaptic GluN2A to a similar degree in wildtype and Neto1/Neto2 knockout mice. However, while colloidal gold only sparsely labeled GluN2B subunits at wildtype synapses, immunolabeling for postsynaptic GluN2B was strongly increased in Neto1/Neto2 knockout mice. In support of these findings, NMDA receptor-mediated postsynaptic currents at the mossy fiber synapse in Neto1 knockout mice exhibited substantially greater sensitivity to the GluN2B antagonist, ifenprodil, than those in wildtype mice. Taken together, the results may indicate that GluN1/GluN2A diheteromeric receptors in wildtype mice become GluN1/GluN2A/GluN2B triheteromeric receptors in Neto1/Neto2 knockout mice. Overall, this study revealed that despite maintained NMDA receptor transmission at the mossy fiber synapse onto CA3 pyramidal cells, the underlying subunits are altered in Neto knockout mice.

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