Institute of Anatomy and Cell Biology, Dept. I, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Graduate School of Systemic Neurosciences, Ludwig-Maximilians-University Munich, Planegg-Martinsried, Germany.
Brain Struct Funct. 2021 Sep;226(7):2125-2151. doi: 10.1007/s00429-021-02315-7. Epub 2021 Jun 28.
Extraocular motoneurons initiate dynamically different eye movements, including saccades, smooth pursuit and vestibulo-ocular reflexes. These motoneurons subdivide into two main types based on the structure of the neuro-muscular interface: motoneurons of singly-innervated (SIF), and motoneurons of multiply-innervated muscle fibers (MIF). SIF motoneurons are thought to provoke strong and brief/fast muscle contractions, whereas MIF motoneurons initiate prolonged, slow contractions. While relevant for adequate functionality, transmitter and ion channel profiles associated with the morpho-physiological differences between these motoneuron types, have not been elucidated so far. This prompted us to investigate the expression of voltage-gated potassium, sodium and calcium ion channels (Kv1.1, Kv3.1b, Nav1.6, Cav3.1-3.3, KCC2), the transmitter profiles of their presynaptic terminals (vGlut1 and 2, GlyT2 and GAD) and transmitter receptors (GluR2/3, NMDAR1, GlyR1α) using immunohistochemical analyses of abducens and trochlear motoneurons and of abducens internuclear neurons (INTs) in macaque monkeys. The main findings were: (1) MIF and SIF motoneurons express unique voltage-gated ion channel profiles, respectively, likely accounting for differences in intrinsic membrane properties. (2) Presynaptic glutamatergic synapses utilize vGlut2, but not vGlut1. (3) Trochlear motoneurons receive GABAergic inputs, abducens neurons receive both GABAergic and glycinergic inputs. (4) Synaptic densities differ between MIF and SIF motoneurons, with MIF motoneurons receiving fewer terminals. (5) Glutamatergic receptor subtypes differ between MIF and SIF motoneurons. While NMDAR1 is intensely expressed in INTs, MIF motoneurons lack this receptor subtype entirely. The obtained cell-type-specific transmitter and conductance profiles illuminate the structural substrates responsible for differential contributions of neurons in the abducens and trochlear nuclei to eye movements.
眼外运动神经元发起动态不同的眼球运动，包括扫视、平滑追踪和前庭眼反射。这些运动神经元根据神经肌肉接口的结构分为两种主要类型：单神经支配（SIF）运动神经元和多神经支配肌纤维（MIF）运动神经元。SIF 运动神经元被认为会引起强烈而短暂/快速的肌肉收缩，而 MIF 运动神经元则引发长时间的缓慢收缩。虽然与适当的功能相关，但与这些运动神经元类型的形态生理差异相关的递质和离子通道特征尚未得到阐明。这促使我们研究电压门控钾、钠和钙离子通道（Kv1.1、Kv3.1b、Nav1.6、Cav3.1-3.3、KCC2）、其突触前末梢递质谱（vGlut1 和 2、GlyT2 和 GAD）和递质受体（GluR2/3、NMDAR1、GlyR1α）在猕猴的展神经和滑车运动神经元以及展神经核间神经元（INTs）中的表达情况，采用免疫组织化学分析。主要发现如下：（1）MIF 和 SIF 运动神经元分别表达独特的电压门控离子通道谱，可能与内在膜特性的差异有关。（2）突触前谷氨酸能突触利用 vGlut2，但不利用 vGlut1。（3）滑车运动神经元接受 GABA 能输入，展神经神经元接受 GABA 和甘氨酸能输入。（4）MIF 和 SIF 运动神经元之间的突触密度不同，MIF 运动神经元接收的末梢较少。（5）谷氨酸能受体亚型在 MIF 和 SIF 运动神经元之间存在差异。虽然 NMDAR1 在 INTs 中强烈表达，但 MIF 运动神经元完全缺乏这种受体亚型。获得的细胞类型特异性递质和电导率谱阐明了结构底物，这些结构底物负责展神经核和滑车核神经元对眼球运动的不同贡献。
