Triheteromeric N-methyl-d-aspartate receptors differentiate synaptic inputs onto pyramidal neurons in somatosensory cortex: Involvement of the GluN3A subunit
详细信息 查看全文
- 作者：J. Pilli ; S.S. Kumar
- 关键词：NMDA receptor subunit composition ; pathway-specificity of synaptic inputs ; GluN3 ; somatosensory cortex ; electrophysiology
- 刊名：Neuroscience
- 出版年：2012
- 出版时间：11 October, 2012
- 年：2012
- 卷：222
- 期：Complete
- 页码：75-88
- 全文大小：1518 K
文摘
N-methyl-d-aspartate receptors (NMDARs) are glutamatergic by virtue of glutamate-binding GluN2 subunits and glycinergic by virtue of glycine-binding GluN1 and GluN3 subunits. The existence, location, and functional-significance of NMDARs containing both GluN2 and GluN3 subunits have as yet remained unelucidated. Here we report on the discovery and characterization of a novel type of NMDARs, found at layer (L)1/primary whisker-motor-cortex inputs onto L5 pyramidal neurons in somatosensory cortex, that are distinct in structure and function from conventional GluN2A-containing NMDARs at thalamic/striatal (Str) inputs onto the same neurons. These receptors had a threshold-like activation at hyperpolarized holding-potentials with strong outward rectification of their current-voltage relationships unlike any known GluN1/GluN2-containing NMDARs. Pharmacology revealed a triheteromeric-receptor with features common to glutamate-activated GluN1/GluN2-containing and glycine-activated GluN1/GluN3-containing diheteromeric NMDARs. However, unlike GluN1/GluN3 receptors, NMDARs at L1 inputs were activated by glutamate and blocked by d-AP5, Ca2+-permeable, and more efficient at integrating and potentiating EPSPs selectively over Str inputs during high-frequency stimulation while obviating the need for AMPAR-mediated depolarization.