Nagaraja Chetan, Ortiz Serena, Murali Akash R, Griffith Theanne N
Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, USA.
Undergraduate Program in Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA.
bioRxiv. 2025 Aug 23:2025.08.22.671861. doi: 10.1101/2025.08.22.671861.
Proprioceptive group Ia afferents detect muscle stretch to guide effortless and purposeful movement and make monosynaptic connections with spinal α-motor neurons to mediate reflexes, such as the stretch reflex. It is thought that proprioceptive Ia afferents target motor neurons of the same spinal segment; yet, how this specificity, if any, is established during early development is unknown. Using spinal cord electrophysiology preparations from neonatal mice of both sexes, we identified a developmental period during which proprioceptive la afferents evoke both segmental and intersegmental responses at monosynaptic latencies. We provide anatomical evidence that motor neurons in the lumbar segment 4 (L4) receive direct input from proprioceptive Ia afferents in L5 during early postnatal development. Intersegmental responses (L4/L5) were prominent at postnatal days (P) 4-7 but were virtually absent by P11-13. To test the role of proprioceptor activity on segmental specification, we analyzed Na1.6 conditional knockout mice (Na1.6), in which proprioceptor signaling is impaired, and found that intersegmental responses persist up to P11-13 but were absent in age-matched floxed controls. We predict this is due to impaired activation of complement signaling pathways, as Na1.6 mice showed reduced C1qA expression in the ventral spinal cord at P9. Consistent with this, C1qA knockout mice also retain intersegmental responses at P11-13. Collectively, these findings identify an important postnatal window during which segmental specificity of proprioceptive circuits emerges and suggest that proprioceptor activity induces C1qA-mediated elimination of excessive intersegmental connectivity.
本体感觉Ia类传入神经检测肌肉拉伸，以引导轻松且有目的的运动，并与脊髓α运动神经元建立单突触连接，以介导反射，如牵张反射。人们认为本体感觉Ia类传入神经靶向同一脊髓节段的运动神经元；然而，这种特异性（如果存在的话）在早期发育过程中是如何建立的尚不清楚。利用来自两性新生小鼠的脊髓电生理制剂，我们确定了一个发育时期，在此期间本体感觉Ia类传入神经在单突触潜伏期诱发节段性和节段间反应。我们提供了解剖学证据，表明在出生后早期发育期间，腰段4（L4）的运动神经元接受来自L5的本体感觉Ia类传入神经的直接输入。节段间反应（L4/L5）在出生后第（P）4 - 7天很明显，但在P11 - 13时几乎不存在。为了测试本体感受器活动在节段特异性方面的作用，我们分析了Na1.6条件性敲除小鼠（Na1.6），其中本体感受器信号传导受损，发现节段间反应持续到P11 - 13，但在年龄匹配的对照小鼠中不存在。我们预测这是由于补体信号通路的激活受损，因为Na1.6小鼠在P9时腹侧脊髓中的CstbA表达降低。与此一致，C1qA敲除小鼠在P11 - 13时也保留节段间反应。总的来说，这些发现确定了一个重要的出生后窗口期，在此期间本体感觉回路的节段特异性出现，并表明本体感受器活动诱导C1qA介导的对过度节段间连接的消除。
