Department of Physiology, Emory University, Atlanta, Georgia 30322, and Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio 45435.
J Neurosci. 2014 Mar 5;34(10):3475-92. doi: 10.1523/JNEUROSCI.4768-13.2014.
Peripheral nerve injury induces permanent alterations in spinal cord circuitries that are not reversed by regeneration. Nerve injury provokes the loss of many proprioceptive IA afferent synapses (VGLUT1-IR boutons) from motoneurons, the reduction of IA EPSPs in motoneurons, and the disappearance of stretch reflexes. After motor and sensory axons successfully reinnervate muscle, lost IA VGLUT1 synapses are not re-established and the stretch reflex does not recover; however, electrically evoked EPSPs do recover. The reasons why remaining IA synapses can evoke EPSPs on motoneurons, but fail to transmit useful stretch signals are unknown. To better understand changes in the organization of VGLUT1 IA synapses that might influence their input strength, we analyzed their distribution over the entire dendritic arbor of motoneurons before and after nerve injury. Adult rats underwent complete tibial nerve transection followed by microsurgical reattachment and 1 year later motoneurons were intracellularly recorded and filled with neurobiotin to map the distribution of VGLUT1 synapses along their dendrites. We found in control motoneurons an average of 911 VGLUT1 synapses; ~62% of them were lost after injury. In controls, VGLUT1 synapses were focused to proximal dendrites where they were grouped in tight clusters. After injury, most synaptic loses occurred in the proximal dendrites and remaining synapses were declustered, smaller, and uniformly distributed throughout the dendritic arbor. We conclude that this loss and reorganization renders IA afferent synapses incompetent for efficient motoneuron synaptic depolarization in response to natural stretch, while still capable of eliciting EPSPs when synchronously fired by electrical volleys.
周围神经损伤会导致脊髓回路发生永久性改变，而这些改变无法通过再生来逆转。神经损伤会导致许多本体感觉 IA 传入性突触（VGLUT1-IR 终扣）从运动神经元中丢失，IA EPSPs 在运动神经元中的减少，以及牵张反射的消失。在运动和感觉轴突成功地重新支配肌肉后，丢失的 IA VGLUT1 突触不会重新建立，牵张反射也不会恢复；然而，电诱发的 EPSPs 会恢复。为什么剩余的 IA 突触可以在运动神经元上引发 EPSPs，但不能传递有用的牵张信号仍然未知。为了更好地理解可能影响其输入强度的 IA VGLUT1 突触的组织变化，我们在神经损伤前后分析了它们在运动神经元整个树突上的分布。成年大鼠接受完全胫神经横断，然后进行显微再附着，一年后对运动神经元进行细胞内记录并填充神经生物素，以绘制 VGLUT1 突触在其树突上的分布。我们发现，在对照组运动神经元中，平均有 911 个 VGLUT1 突触；~62%的突触在损伤后丢失。在对照组中，VGLUT1 突触集中在近端树突上，在那里它们聚集在紧密的簇中。损伤后，大多数突触丢失发生在近端树突上，剩余的突触被离散化，变小，均匀分布在整个树突上。我们得出结论，这种丢失和重组使 IA 传入性突触不能有效地使运动神经元突触去极化以响应自然牵张，而当它们被电脉冲同步激发时，仍然能够引发 EPSPs。
