Eugène Daniel, Deforges Sèverine, Vibert Nicolas, Vidal Pierre-Paul
Laboratoire de Neurobiologie des Réseaux Sensorimoteurs, Université Paris Descartes-CNRS, Paris, France.
Ann N Y Acad Sci. 2009 May;1164:180-7. doi: 10.1111/j.1749-6632.2008.03727.x.
Mutant mice are a good model to study to what extent the postnatal activity of sensory afferents is necessary for the maturation of central neurons. In particular, the question arises whether the signals carried by the first-order vestibular neurons, which encode information on the head movement of pups, are necessary for the maturation of second-order vestibular neurons. To address that question, juvenile and adult transgenic, vestibular-deficient mutants where a null mutation of the KCNE1 potassium-channel gene leads to degeneration of all hair cells of the inner ear just after birth were studied. These KCNE1(-/-) mutants are deaf and show quasi-constant head bobbing and a permanent shaker/waltzer phenotype. This behavior is not due to persistent abnormalities of the membrane properties of central vestibular neurons, because their maturation is delayed but not impaired by the absence of sensory vestibular information. On the other hand, the data shed light on how the membrane properties of vestibular neurons might be modified according to functional requirements or following lesions. The expression levels of the protein calretinin that regulates the intracellular free-calcium concentration in central vestibular neurons could play a major role both in intact animals and following labyrinthectomy. By comparing the KCNE1(-/-) mutant mice to other vestibular-deficient animals, it was concluded that the suppression of vestibular inputs during a "critical period" of postnatal development can induce a permanent circling behavior, but that this phenotype is not always due to congenital vestibular deficiency.
突变小鼠是研究感觉传入神经的产后活动在多大程度上对中枢神经元成熟所必需的良好模型。特别是，出现了一个问题，即编码幼崽头部运动信息的一级前庭神经元所携带的信号，对于二级前庭神经元的成熟是否必要。为了解决这个问题，研究了幼年和成年转基因前庭缺陷突变体，其中KCNE1钾通道基因的无效突变导致出生后内耳所有毛细胞退化。这些KCNE1(-/-)突变体失聪，并表现出准恒定的头部摆动和永久性的摇晃/华尔兹表型。这种行为并非由于中枢前庭神经元膜特性的持续异常，因为它们的成熟虽有延迟，但并未因前庭感觉信息的缺失而受损。另一方面，这些数据揭示了前庭神经元的膜特性可能如何根据功能需求或损伤进行改变。调节中枢前庭神经元细胞内游离钙浓度的钙视网膜蛋白的表达水平，在完整动物和迷路切除术后可能都起着主要作用。通过将KCNE1(-/-)突变小鼠与其他前庭缺陷动物进行比较，得出结论：在产后发育的“关键期”抑制前庭输入可诱导永久性的转圈行为，但这种表型并不总是由于先天性前庭缺陷。
