Shallow Molly C, Tian Lucy, Higashikubo Bryan T, Lin Hudson, Lefton Katheryn B, Chen Siyu, Dougherty Joseph D, Culver Joe P, Lambo Mary E, Hengen Keith B
Department of Biology, Washington University in Saint Louis, Saint Louis, Missouri 63130.
Department of Neuroscience, Washington University in Saint Louis, Saint Louis, Missouri 63110.
eNeuro. 2025 Aug 19;12(8). doi: 10.1523/ENEURO.0252-25.2025. Print 2025 Aug.
The development of motor control over sensory organs is a critical milestone, enabling active exploration and shaping of the sensory environment. Whether the onset of sensory organ motor control directly influences the development of corresponding sensory cortices remains unknown. Here, we confirm and exploit the late onset of whisking behavior in mice to address this question in the somatosensory system. Using ex vivo electrophysiology, we describe a transient increase in the intrinsic excitability of excitatory neurons in layer IV of the barrel cortex, which processes whisker input, immediately following the onset of active whisking on postnatal days 13 and 14. This increase in neuronal gain is specific to layer IV, independent of changes in synaptic strength, and requires prior sensory experience. Further, these effects are not expressed in inhibitory interneurons in barrel cortex. The transient increase in excitability is not evident in layer II/III of barrel cortex or in the visual cortex upon eye opening, suggesting a unique interaction between the development of active sensing and the thalamocortical input layer in the somatosensory isocortex. Predictive modeling indicates that, immediately following the onset of active whisking, changes in active membrane conductances alone can reliably distinguish neurons in control but not whisker-deprived hemispheres. Our findings demonstrate an experience-dependent, lamina-specific refinement of neuronal excitability tightly linked to the emergence of active whisking. This transient increase in the gain of the thalamic input layer coincides with a critical period for synaptic plasticity in downstream layers, suggesting a role in cortical maturation and sensory processing.
对感觉器官的运动控制发展是一个关键的里程碑，它使机体能够积极探索并塑造感觉环境。感觉器官运动控制的起始是否直接影响相应感觉皮层的发育仍然未知。在这里，我们确认并利用小鼠触须运动行为出现较晚这一特点，来解决躯体感觉系统中的这个问题。通过离体电生理学方法，我们描述了在出生后第13天和第14天主动触须运动开始后，处理触须输入的桶状皮层IV层兴奋性神经元的内在兴奋性出现短暂增加。这种神经元增益的增加特定于IV层，与突触强度的变化无关，并且需要先前的感觉经验。此外，这些效应在桶状皮层的抑制性中间神经元中并未表现出来。兴奋性的短暂增加在桶状皮层II/III层或睁眼时的视觉皮层中并不明显，这表明主动感觉的发展与躯体感觉同型皮层中的丘脑皮质输入层之间存在独特的相互作用。预测模型表明，在主动触须运动开始后，仅主动膜电导的变化就能可靠地区分对照半球而非触须剥夺半球中的神经元。我们的研究结果表明，神经元兴奋性存在经验依赖性、层特异性的优化，且与主动触须运动行为的出现紧密相关。丘脑输入层增益的这种短暂增加与下游层突触可塑性的关键期相吻合，表明其在皮层成熟和感觉处理中发挥作用。
