Lateralized feeding behavior is associated with asymmetrical neuroanatomy and lateralized gene expressions in the brain in scale-eating cichlid fish

Lateralized behavior (‘handedness’) is unusual, but consistently found across diverse animal lineages, including humans. It is thought to reflect brain anatomical and/or functional asymmetries, but its neuro-molecular mechanisms remain largely unknown. Lake Tanganyika scale-eating cichlid fish, Perissodus microlepis show pronounced asymmetry in their jaw morphology as well as handedness in feeding behavior – feeding scales preferentially only from one or the other side of their victims. This makes them an ideal model in which to investigate potential laterality in neuroanatomy and transcription in the brain in relation to behavioral handedness. After determining behavioral handedness in P. microlepis (preferred attack side), we estimated the volume of the hemispheres of brain regions and captured their gene expression profiles. Our analyses revealed that the degree of behavioral handedness is mirrored at the level of neuroanatomical asymmetry, particularly in the tectum opticum. Transcriptome analyses showed that different brain regions (tectum opticum, telencephalon, hypothalamus and cerebellum) display distinct expression patterns, potentially reflecting their developmental interrelationships. For numerous genes in each brain region, their extent of expression differences between hemispheres was found to be correlated with the degree of behavioral lateralization. Interestingly, the tectum opticum and telencephalon showed divergent biases on the direction of up- or down-regulation of the laterality candidate genes (e.g., grm2) in the hemispheres, highlighting the connection of handedness with gene expression profiles and the different roles of these brain regions. Hence, handedness in predation behavior may be caused by asymmetric size of brain hemispheres and also by lateralized gene expressions in the brain.

偏侧化行为（Lateralized behavior，又称“利手性（handedness）”）虽不常见，但在包括人类在内的多种动物类群中均有稳定发现。该现象被认为反映了大脑解剖结构与/或功能的不对称性，但其神经分子机制在很大程度上仍未明确。坦噶尼喀湖食鳞丽鱼（小鳞突丽鱼，*Perissodus microlepis*）不仅颌骨形态呈现显著不对称性，其进食行为也存在利手性——会优先从猎物的单侧体表取食鱼鳞。这使其成为研究与行为利手性相关的大脑神经解剖及转录组偏侧化的理想实验模型。在明确小鳞突丽鱼的行为利手性（即偏好的攻击侧）后，我们对其各脑区两侧的体积进行了评估，并获取了相应的基因表达谱。本研究分析显示，行为利手性的程度与神经解剖不对称性水平呈对应关系，这一现象在视顶盖（tectum opticum）中尤为显著。转录组分析表明，不同脑区（视顶盖、端脑（telencephalon）、下丘脑（hypothalamus）以及小脑（cerebellum））均具有独特的基因表达模式，这可能反映了它们在发育过程中的相互关联。在每个脑区的众多基因中，其两侧半球的表达差异程度均与行为偏侧化程度显著相关。有趣的是，视顶盖与端脑在偏侧化候选基因（如代谢型谷氨酸受体2（grm2））的半球间上调或下调方向上呈现出相反的偏向性，这凸显了利手性与基因表达谱之间的关联，以及这些脑区各自的功能差异。综上，捕食行为中的利手性可能由大脑半球的不对称体积以及大脑内的偏侧化基因表达共同导致。