Jain Ekta, Lussiez Rudy, Flouty Oliver, Bharmauria Vishal, Molotchnikoff Stéphane
Neurophysiology of Visual System, Département de Sciences Biologiques, Université de Montréal, Montréal, Québec, Canada.
The Tampa Human Neurophysiology Lab & Department of Neurosurgery, Brain and Spine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States.
J Neurophysiol. 2025 Jul 1;134(1):372-381. doi: 10.1152/jn.00151.2025. Epub 2025 Jun 23.
Neural plasticity-the ability of nervous system to adapt its structure, function, or connections in response to stimuli-can be induced in adulthood through specific protocols, such as visual adaptation, referring to the imposition of a preferred/nonpreferred stimulus to a neuron(s) under investigation. Neuronal orientation selectivity-the preference for specific stimulus orientations-is fundamental to visual cortex organization across species and can be modified using adaptation or pharmacological protocols. Structural, molecular, and physiological properties of neurons, including activity-dependent protein synthesis, play a pivotal role during adaptation. In this study, we investigated the effect of anisomycin, an antibiotic that inhibits protein synthesis by interfering with peptidyl transferase activity in eukaryotic ribosomes, on neuroplastic changes in the mouse visual cortex. We first confirm that adaptation induces shifts in orientation tuning; however, anisomycin prevents these adaptation-induced shifts. Thus, as expected, anisomycin altered the relationship between orientation selectivity and amplitude of shifts, reflecting a stabilization of preferred orientation rather than a biological decoupling of these features. This suggests that protein synthesis is necessary for the OSI-dependent modulation of tuning properties, not merely for preventing tuning shifts. Overall, our findings demonstrate that anisomycin obstructs cortical neuroplasticity, suggesting its potential for suppressing unwanted plasticity in therapeutic applications. We demonstrate that anisomycin, a protein synthesis inhibitor, blocks adaptation-induced shifts in neuronal orientation tuning in the mouse visual cortex. Although adaptation typically reshapes orientation selectivity, anisomycin disrupts this process and alters the relationship between selectivity and shift amplitude. These findings suggest that anisomycin interferes with neural signal transmission and cortical plasticity. Our results highlight anisomycin's potential to suppress maladaptive plasticity, offering insights into mechanisms of experience-dependent cortical reorganization and possible therapeutics for aberrant plasticity.
神经可塑性——神经系统响应刺激而改变其结构、功能或连接的能力——在成年期可通过特定方案诱导产生，如视觉适应，即对所研究的一个或多个神经元施加偏好/非偏好刺激。神经元方向选择性——对特定刺激方向的偏好——是跨物种视觉皮层组织的基础，并且可以通过适应或药理学方案进行改变。神经元的结构、分子和生理特性，包括与活动相关的蛋白质合成，在适应过程中起着关键作用。在本研究中，我们研究了茴香霉素（一种通过干扰真核核糖体中的肽基转移酶活性来抑制蛋白质合成的抗生素）对小鼠视觉皮层神经可塑性变化的影响。我们首先证实适应会诱导方向调谐的变化；然而，茴香霉素会阻止这些由适应引起的变化。因此，正如预期的那样，茴香霉素改变了方向选择性与变化幅度之间的关系，这反映了偏好方向的稳定，而不是这些特征的生物学解耦。这表明蛋白质合成对于依赖于方向选择性指数（OSI）的调谐特性调制是必要的，而不仅仅是为了防止调谐变化。总体而言，我们的研究结果表明茴香霉素会阻碍皮质神经可塑性，这表明其在治疗应用中具有抑制不必要可塑性的潜力。我们证明，蛋白质合成抑制剂茴香霉素可阻断小鼠视觉皮层中由适应引起的神经元方向调谐变化。虽然适应通常会重塑方向选择性，但茴香霉素会破坏这一过程并改变选择性与变化幅度之间的关系。这些发现表明茴香霉素会干扰神经信号传递和皮质可塑性。我们的结果突出了茴香霉素抑制适应不良可塑性的潜力，为经验依赖性皮质重组机制及异常可塑性的可能治疗方法提供了见解。
