Department of Bioengineering and Therapeutic Sciences, Programs in Human Genetics and Biological Sciences, The Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, California 94143-2811, USA.
J Neurosci. 2011 Jan 5;31(1):214-24. doi: 10.1523/JNEUROSCI.3339-10.2011.
The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.
斑马鱼的伪装反应是一种先天的“硬连线”行为，为探索神经回路的组装和功能提供了极好的机会。此外，伪装反应对乙醇敏感，使其成为一个易于理解乙醇如何影响神经回路发育和功能的系统。在这里，我们报告了促肾上腺皮质素释放因子 (CRF) 作为伪装反应途径的关键组成部分的鉴定。我们进一步表明，乙醇对视觉感觉系统或黑色素细胞没有直接作用，而是作用于视网膜神经节细胞的下游，并且需要 CRF-促黑激素原途径来发挥其对伪装的作用。用乙醇处理以及改变光暴露，从而改变进入伪装回路的感觉输入，都会强烈改变 CRF 在神经元亚群中的表达。这种 crf 表达的乙醇诱导或光诱导可塑性都需要环腺苷酸 5 和细胞外信号调节激酶 (ERK) 的活性。这些结果揭示了一种肽能途径在伪装中的重要作用，这种作用受光调节，并在与滥用和焦虑缓解相关的浓度下受乙醇影响，以 cAMP 依赖性和 ERK 依赖性的方式进行。我们得出结论，这种乙醇调节的伪装反应代表了一个新颖而相关的系统，可用于对受光调节且对乙醇敏感的神经回路进行分子遗传剖析。
