Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability

Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability
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DOI:
10.1096/fj.15-279257
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发表时间:
2016-02-01
期刊:
影响因子:
4.8
通讯作者:
O'Connor, Vincent
O'Connor, Vincent
中科院分区:
生物学2区
文献类型:
--
作者:
Dalliere, Nicolas;Bhatla, Nikhil;O'Connor, Vincent

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动物如何将进食与食物供应相匹配是能量稳态的关键问题。我们在线虫秀丽隐杆线虫中解决了这一问题,线虫通过调节咽部活动(泵送)将进食与其食物(细菌)的存在结合起来。我们在野生型和突变型蠕虫中,在食物存在的情况下以及在食物剥夺的延长时间过程中对泵送进行评分,以确定适应行为的神经基质。去除食物最初抑制泵,但2小时后,这是伴随着间歇性的高活性。我们表明,泵是微调的上下文特定的神经机制,并强调在没有食物的情况下,抑制性amatergic和兴奋性胆碱能/肽能驱动器的关键作用。此外,突触蛋白CAPS-31(calcium-activated protein for secretion,CAPS)通过一种抑制途径发挥作用,这种抑制途径不能用先前确定的CAPS-31/CAPS对神经肽或谷氨酸传递的贡献来解释。抽吸不受咽部和中枢神经系统之间连接的激光消融的影响,表明信号是体液的或肠系统固有的。这个框架中,控制是通过微调兴奋性和抑制性驱动器介导的共振与哺乳动物下丘脑控制的喂养,并表明,这种基本的动物行为的基本调节可能是保守的,通过从线虫进化到人类。
How an animal matches feeding to food availability is a key question for energy homeostasis. We addressed this in the nematode Caenorhabditis elegans, which couples feeding to the presence of its food (bacteria) by regulating pharyngeal activity (pumping). We scored pumping in the presence of food and over an extended time course of food deprivation in wild-type and mutant worms to determine the neural substrates of adaptive behavior. Removal of food initially suppressed pumping but after 2 h this was accompanied by intermittent periods of high activity. We show pumping is fine-tuned by context-specific neural mechanisms and highlight a key role for inhibitory glutamatergic and excitatory cholinergic/peptidergic drives in the absence of food. Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission. Pumping was unaffected by laser ablation of connectivity between the pharyngeal and central nervous system indicating signals are either humoral or intrinsic to the enteric system. This framework in which control is mediated through finely tuned excitatory and inhibitory drives resonates with mammalian hypothalamic control of feeding and suggests that fundamental regulation of this basic animal behavior may be conserved through evolution from nematode to human.