Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour
Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour
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DOI：
10.1111/j.1460-9568.2004.03527.x
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发表时间：
2004-08-01
影响因子：
3.4
通讯作者：
Buchner, E
中科院分区：
文献类型：
--
作者：
Godenschwege, TA;Reisch, D;Buchner, E
脊椎动物突触素是一种丰富的突触小泡磷蛋白，已被认为通过依赖磷酸化控制突触小泡的运动来精细调节神经递质的释放。然而，由于所有三种小鼠突触素基因的敲除而导致所有突触素亚型完全缺失的后果尚未得到研究。在果蝇中，一个突触素基因编码几个亚型，并在大多数突触终末表达。因此，果蝇突触素基因的靶向缺失消除了通过其他亚型进行功能性敲除互补的可能性。出乎意料的是，突触蛋白缺失突变的果蝇在大脑形态上没有明显的缺陷，在行为上也没有观察到明显的质变。对已鉴定的幼虫神经肌肉标本的模型突触的超微结构分析表明，野生型和突变型之间没有差异，在该突触上的自发或诱发的兴奋性连接电位在5赫兹的刺激频率下是正常的。然而，当对几种行为反应进行量化分析时，突变型和野生型苍蝇之间的具体差异被注意到。成人的运动活动、高模式速度下的视觉运动反应、翅膀跳动频率和视觉模式偏好被修改。突触素突变果蝇表现出更快的嗅觉跳跃反应习惯化，增强的酒精耐受性，以及使用三种不同范例测量的学习和记忆方面的显著缺陷。幼虫的行为缺陷在另一篇论文中有描述。我们得出结论，果蝇突触蛋白在神经系统功能中发挥着重要作用，这在细胞水平上是微妙的，但在复杂的行为中表现出来。
Vertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been proposed to fine-regulate neurotransmitter release by phosphorylation-dependent control of synaptic vesicle motility. However, the consequences of a total lack of all synapsin isoforms due to a knock-out of all three mouse synapsin genes have not yet been investigated. In Drosophila a single synapsin gene encodes several isoforms and is expressed in most synaptic terminals. Thus the targeted deletion of the synapsin gene of Drosophila eliminates the possibility of functional knock-out complementation by other isoforms. Unexpectedly, synapsin null mutant flies show no obvious defects in brain morphology, and no striking qualitative changes in behaviour are observed. Ultrastructural analysis of an identified 'model' synapse of the larval nerve muscle preparation revealed no difference between wild-type and mutant, and spontaneous or evoked excitatory junction potentials at this synapse were normal up to a stimulus frequency of 5 Hz. However, when several behavioural responses were analysed quantitatively, specific differences between mutant and wild-type flies are noted. Adult locomotor activity, optomotor responses at high pattern velocities, wing beat frequency, and visual pattern preference are modified. Synapsin mutant flies show faster habituation of an olfactory jump response, enhanced ethanol tolerance, and significant defects in learning and memory as measured using three different paradigms. Larval behavioural defects are described in a separate paper. We conclude that Drosophila synapsins play a significant role in nervous system function, which is subtle at the cellular level but manifests itself in complex behaviour.