NMDA receptors are heteromeric complexes that contribute to excitatory synaptic transmission and plasticity. The presence of specific variants of GluN2 subunits in these complexes enables diversity in NMDA receptor function and regulation. At brain synapses, there is a switch from slow GluN2B-mediated NMDA receptors to faster GluN2A-dominated NMDA receptors as well as an increase in the ratio of AMPA to NMDA receptors during early postnatal development. This glutamate receptor switch is observed across brain regions and is critical for synaptic maturation, circuit development, and associative learning. However, whether a similar receptor subunit switch occurs within pain processing neurons in the developing spinal cord remains untested. To investigate this, we performed whole-cell patch clamp recordings of excitatory synaptic responses from lamina II dorsal horn neurons of one to three week-old rats. We found that GluN2B and GluN2A both prominently contribute to NMDA receptor responses at neonatal lamina II synapses, with a small contribution from GluN2D as well. Surprisingly, we found that this molecular identity of NMDA receptor responses as well as the relative contribution of AMPA receptors versus NMDA receptors did not change at lamina II synapses across early postnatal development (P7 to P21). The lack of a developmental switch and persistence of slow-decaying GluN2B- and GluN2D-mediated synaptic responses throughout neuronal maturation in the dorsal horn has implications for understanding both the regulation of synaptic glutamatergic receptors as well as spinal mechanisms of pain processing.

中文翻译：

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NMDA受体亚型对出生后早期整个椎板II脊髓神经元中突触反应的保守贡献。

NMDA受体是异源复合物，有助于兴奋性突触传递和可塑性。这些复合物中GluN2亚基的特定变体的存在使得NMDA受体功能和调节具有多样性。在脑突触中，从早期GluN2B介导的NMDA受体向快速GluN2A为主的NMDA受体转变，并且在出生后早期发育期间AMPA与NMDA受体的比率增加。在整个大脑区域都可以观察到这种谷氨酸受体的转换，这对于突触成熟，电路发展和相关学习至关重要。然而，在发育中的脊髓的疼痛处理神经元内是否发生类似的受体亚单位转换仍未得到测试。为了对此进行调查，我们对一到三周大的大鼠的椎板II背角神经元进行了兴奋性突触反应的全细胞膜片钳记录。我们发现，GluN2B和GluN2A都对新生儿椎板II突触中的NMDA受体应答做出了显着贡献，而GluN2D的贡献也很小。出乎意料的是，我们发现，NMDA受体应答的这种分子同一性以及AMPA受体与NMDA受体的相对贡献在整个出生后早期的椎板II突触中没有改变（P7至P21）。在背角整个神经元成熟过程中缺乏发育转换和缓慢衰减的GluN2B和GluN2D介导的突触反应的持久性，对于理解突触谷氨酸能受体的调节以及疼痛处理的脊柱机制都有影响。