Molecular Neurogenetic studies on thermosensation ane temperature memory formatio

通过与Nef实验室的合作，我们发现神经元特异性钙传感器NCS-1是一种进化过程中高度保守的蛋白质，对热趋向性至关重要。Ncs-1敲除动物在；isothermoal跟踪。通过将野生型NCS-1重新引入AIY中间神经元（一个热亲和性网络的关键组成部分），可以挽救基因敲除表型。丧失NCS-1的功能形式：不能结合钙不能恢复热致性，而过表达NCS-1增强等温跟踪行为。因此，通过钙传感器NCS-1的适当钙信号传导定义了一条对秀丽隐杆线虫的联想学习和记忆至关重要的新途径。Ttx-1突变体表现为低温表型。在与Sengupta实验室的合作中，我们发现ttx-1编码高度保守的OTX/OTD同源结构域蛋白家族的一个成员，并在AFD神经元中表达。ttx-1的错误表达足以使其他感觉神经元转变为afd样命运。秀丽隐杆线虫在钙调神经磷酸酶a亚基TAX-6中携带功能缺失突变，表现出多性异常，包括许多异常的感觉行为。热感觉中的tax-6突变缺陷与AFD热感觉神经元的过度激活是一致的。相反，TAX-6的组成激活导致与AFD神经元失活一致的行为表型。在嗅觉神经元中，税收-6突变体对awc感知的气味的嗅觉反应受损是由过度适应引起的，而过度适应被导致嗅觉适应缺陷的突变所抑制。综上所述，我们的研究结果表明，刺激诱发的钙进入激活了钙调神经磷酸酶，而钙调神经磷酸酶反过来负调控了感觉信号的多个方面。

In collaboration with Nef lab, we show that the neuron-specific calcium sensor NCS-1, a highly conserved protein through evolution, is essential for thermotaxis. ncs-1 knockout animals show strong defects in ; isothermoal tracking. The knockout phenotype can be rescued by re-introducing wild-type NCS-1 into the AIY interneuron, a key component of the thermotaxis network. A loss of function form of NCS-1 : unable to bind calcium does not restore thermotaxis, whereas overexpression of NCS-1 enhances isothermal tracking behavior. Thus, proper calcium signaling via the calcium sensor NCS-1 defines a novel pathway that is essential for associative learning and memory in C. elegans. ttx-1 mutants show cryophylic phenotype. In collaboration with Sengupta lab, we show that ttx-1 encodes a member of the highly conserved OTX/OTD homeodomain protein family, and is expressed in the AFD neurons. Misexpression of ttx-1 is sufficient to convert other sensory neurons to AFD-like fate. C. elegans animals bearing a loss-of-function mutation in TAX-6, a calcineurin A subunit, exhibit pleiotropic abnormalities including many aberrant sensory behaviors. The tax-6 mutant defect in thermosensation is consistent with hyperactivation of the AFD thermosensory neurons. Conversely, constitutive activation of TAX-6 causes a behavioral phenotype consistent with inactivation of AFD neurons. In olfactory neurons, the impaired olfactory response of tax-6 mutants to an AWC-sensed odorant is caused by hyper-adaptation, which is suppres'sible by a mutation causing defective olfactory adaptation. Taken together, our results suggest that stimulus-evoked calcium entry activates calcineurin, which in turn negatively regulates multiple aspects of sensory signaling.