Data from: Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans

<b>Abstract</b><br/>Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented – animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article we use behavioral neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner. We show that the Caenorhabditis elegans orthologs of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1, and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs. In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype, i.e. larger mechanosensory responses than wild-type. Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.

摘要
习惯化（habituation）是一类广泛存在的非联想学习形式，其核心表现为机体对重复刺激的反应逐渐减弱，且该效应无法通过感觉适应或运动疲劳加以解释。习惯化的关键特征之一是其对训练刺激呈现速率的敏感性：动物面对更快频率的刺激时，习惯化进程会更快。然而，这种依赖于刺激间隔（interstimulus interval, ISI）的习惯化特征背后的分子机制，迄今仍未明确。
本文以秀丽隐杆线虫（Caenorhabditis elegans）为研究模型，通过行为学、神经遗传学与生物信息学分析，首次鉴定出以依赖刺激间隔的方式调控习惯化的分子。研究表明，秀丽隐杆线虫中钙/钙调蛋白依赖性激酶CaMK1/4的直系同源物CMK-1，以及O-连接N-乙酰葡糖胺（O-linked N-acetylglucosamine, O-GlcNAc）转移酶OGT-1，均在初级感觉神经元中发挥功能：在短刺激间隔下抑制习惯化，而在长刺激间隔下促进习惯化。此外，cmk-1与ogt-1突变体均呈现出罕见的机械感觉超敏表型，即其机械感觉反应强度高于野生型个体。
综上，本研究鉴定出两个在感觉神经元中行使功能的保守基因，它们以依赖刺激间隔的方式调控习惯化，为这一普遍存在、随刺激递送速率不同而呈现不同特性的习惯化现象的分子机制，提供了首个阐释。