Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Mol Brain. 2020 Mar 5;13(1):31. doi: 10.1186/s13041-020-00566-9.
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.
NMDA 受体是异源寡聚复合物，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 NMDA 受体功能和调节具有多样性。在大脑突触中，存在从慢 GluN2B 介导的 NMDA 受体向更快的 GluN2A 主导的 NMDA 受体的转变，以及在出生后早期发育过程中 AMPA 与 NMDA 受体比值的增加。这种谷氨酸受体转换在大脑区域中都有观察到，对突触成熟、回路发育和联想学习至关重要。然而，在发育中的脊髓中的疼痛处理神经元中是否发生类似的受体亚基转换仍未得到检验。为了研究这一点，我们对 1 至 3 周龄大鼠背角 II 层背角神经元的兴奋性突触反应进行了全细胞膜片钳记录。我们发现 GluN2B 和 GluN2A 都在新生背角 II 层突触中对 NMDA 受体反应有显著贡献，GluN2D 也有少量贡献。令人惊讶的是，我们发现 NMDA 受体反应的这种分子特征以及 AMPA 受体与 NMDA 受体的相对贡献在背角 II 层突触中在整个出生后早期发育过程中（P7 至 P21）并没有改变。缺乏发育性转变以及在背角神经元成熟过程中慢衰减的 GluN2B 和 GluN2D 介导的突触反应的持续存在，对理解突触谷氨酸受体的调节以及疼痛处理的脊髓机制都有影响。
