Normal Distribution of VGLUT1 Synapses on Spinal Motoneuron Dendrites and Their Reorganization after Nerve Injury
Normal Distribution of VGLUT1 Synapses on Spinal Motoneuron Dendrites and Their Reorganization after Nerve Injury
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DOI：
10.1523/jneurosci.4768-13.2014
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发表时间：
2014-03-05
影响因子：
5.3
通讯作者：
Alvarez, Francisco J.
中科院分区：
文献类型：
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作者：
Rotterman, Travis M.;Nardelli, Paul;Alvarez, Francisco J.
周围神经损伤引起脊髓回路的永久性改变，不能通过再生逆转。神经损伤引起运动神经元的许多本体感受性IA传入突触（VGLUT 1-IR终扣）的丢失，运动神经元中IA EPSP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神经支配肌肉后，失去的IA VGLUT 1突触不能重新建立，牵张反射不能恢复;然而，电诱发的EPSP可以恢复。为什么剩余的IA突触可以引起运动神经元上的EPSP，但不能传递有用的牵拉信号的原因尚不清楚。为了更好地了解VGLUT 1 IA突触组织的变化，可能会影响他们的输入强度，我们分析了他们的分布在整个树突状乔木的运动神经元神经损伤前后。成年大鼠进行完全胫神经横断，然后显微外科再附着和1年后运动神经元细胞内记录和充满神经生物素映射VGLUT 1突触沿着他们的树突的分布。我们发现，在对照运动神经元中，平均有911个VGLUT 1突触;其中62%在损伤后丢失。在对照组中，VGLUT 1突触集中在近端树突，在那里它们被紧密地聚集在一起。损伤后，大多数突触丢失发生在近端树突，其余突触分散，较小，均匀分布在整个树突乔木。我们的结论是，这种损失和重组，使IA传入突触无能的有效运动神经元突触去极化响应自然拉伸，同时仍然能够引起EPSP时，同步发射的电齐射。
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; similar to 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.