Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210009, China.
Neurosci Bull. 2011 Apr;27(2):69-82. doi: 10.1007/s12264-011-1152-z.
To perform the modulation of an assay system for the sensory integration of 2 sensory stimuli that inhibit each other.
The assay system for assessing the integrative response to 2 reciprocally-inhibitory sensory stimuli was modulated by changing the metal ion barrier. Moreover, the hen-1, ttx-3 and casy-1 mutants having known defects in integrative response were used to evaluate the modulated assay systems. Based on the examined assay systems, new genes possibly involved in the sensory integration control were identified.
In the presence of different metal ion barriers and diacetyl, locomotion behaviors, basic movements, pan-neuronal, cholinergic and GABAergic neuronal GFP expressions, neuronal development, structures of sensory neurons and interneurons, and stress response of nematodes in different regions of examined assay systems were normal, and chemotaxis toward different concentrations of diacetyl and avoidance of different concentrations of metal ions were inhibited. In the first group, most of the nematodes moved to diacetyl by crossing the barrier of Fe(2+), Zn(2+), or Mn(2+). In the second group, almost half of the nematodes moved to diacetyl by crossing the barrier of Ag(+), Cu(2+), Cr(2+), or Cd(2+). In the third group, only a small number of nematodes moved to diacetyl by crossing the barrier of Pb(2+) or Hg(2+). Moreover, when nematodes encountered different metal ion barriers during migration toward diacetyl, the percentage of nematodes moving back and then turning and that of nematodes moving straight to diacetyl were very different. With the aid of examined assay systems, it was found that mutations of fsn-1 that encodes a F-box protein, and its target scd-2 that encodes a receptor tyrosine kinase, caused severe defects in integrative response, and the sensory integration defects of fsn-1 mutants were obviously inhibited by scd-2 mutation.
Based on the nematode behaviors in examined assay systems, 3 groups of assay systems were obtained. The first group may be helpful in evaluating or identifying the very subtle deficits in sensory integration, and the third group may be useful for the final confirmation of sensory integration defects of mutants identified in the first or the second group of assay systems. Furthermore, the important association of sensory integration regulation with stabilization or destabilization of synaptic differentiation may exist in C. elegans.
对相互抑制的 2 种感觉刺激的感觉整合测定系统进行调制。
通过改变金属离子屏障来调节评估对 2 种相互抑制的感觉刺激的整合反应的测定系统。此外，还使用具有已知整合反应缺陷的 hen-1、ttx-3 和 casy-1 突变体来评估调制的测定系统。基于所检查的测定系统，鉴定了可能参与感觉整合控制的新基因。
在存在不同金属离子屏障和双乙酰的情况下，线虫的运动行为、基本运动、全神经元、胆碱能和 GABA 能神经元 GFP 表达、神经元发育、感觉神经元和中间神经元的结构以及不同区域的线虫对不同浓度双乙酰的趋化性和对不同浓度金属离子的回避反应均正常，但对不同浓度双乙酰的趋化性和对不同浓度金属离子的回避反应受到抑制。在第一组中，大多数线虫通过穿过 Fe(2+)、Zn(2+)或 Mn(2+)的屏障移动到双乙酰。在第二组中，几乎一半的线虫通过穿过 Ag(+)、Cu(2+)、Cr(2+)或 Cd(2+)的屏障移动到双乙酰。在第三组中，只有少数线虫通过穿过 Pb(2+)或 Hg(2+)的屏障移动到双乙酰。此外，当线虫在向双乙酰迁移过程中遇到不同的金属离子屏障时，线虫返回然后转弯的百分比和线虫直接向双乙酰移动的百分比非常不同。借助所检查的测定系统，发现编码 F-box 蛋白的 fsn-1 突变及其靶标 scd-2 突变，编码受体酪氨酸激酶，导致整合反应严重缺陷，fsn-1 突变体的感觉整合缺陷明显被 scd-2 突变抑制。
基于线虫在检查测定系统中的行为，获得了 3 组测定系统。第一组可能有助于评估或识别感觉整合的非常细微缺陷，而第三组可能有助于最终确认第一组或第二组测定系统中鉴定的突变体的感觉整合缺陷。此外，C. elegans 中感觉整合调节与突触分化的稳定或不稳定之间可能存在重要联系。
