A retino-collicular mechanism segregates visual from somatosensory circuits at perinatal life in mice. A retino-collicular mechanism segregates visual from somatosensory circuits at perinatal life in mice

Mature cortical sensory areas are specialized to process unique sensory stimuli. Recent evidence shows that in the mouse embryo sensory cortices are prepared to respond to an incoming input from the periphery. However, whether these sensory circuits originate as modality specific modules, or they are segregated over time remains unknown. Here, we demonstrate that visual and somatosensory circuits originate as functionally intermingled modules, as whisker-pad stimulations at prenatal life led to a multimodal response activating both primary visual and somatosensory cortices. This multimodal response is switched to unimodal at birth via the superior colliculus, a midbrain structure where both modalities converge. Retinal afferent to the superior colliculus prompts the gating of visual from somatosensory circuits achieving sensory modality specificity at birth. Blocking stage I retinal waves resulted in prolonged convergence of somatosensory and visual circuits at the superior colliculus, which led to long-term consequences in the molecular identity of the superior colliculus and caused defects in eye-specific segregation and retinotopy. Hence, the superior colliculus stands as a key developmental regulator of sensory circuits by channeling modality stimuli to their appropriate sensory pathway. Overall design: Bulk RNA-seq of superficial and deep layers from superior colliculus at P6 after intraocular injections of 50 mM carbenoxolone (cbx, Merck, C4790) or saline into the vitreous humor of the eye at P0-P1. The bulk tissue were microdissected (three brains were pooled for each sample) and the total RNA was extracted as in previous publication (Moreno-Juan et al., 2017).

成熟的皮层感觉区具备专门处理独特感觉刺激的功能。近期研究证据表明，小鼠胚胎的感觉皮层已具备响应外周传入信号的能力。然而，这些感觉环路究竟起源于模态特异性模块，还是随时间逐步分离形成，目前仍不明确。本研究证实，视觉与躯体感觉环路最初以功能上相互混杂的模块形式出现：胚胎时期触须垫受到刺激时，会引发多模态反应，同时激活初级视觉皮层与初级躯体感觉皮层。该多模态反应会在出生时通过上丘（superior colliculus）转换为单模态反应——上丘是中脑中同时接收两种模态信号的脑区。投射至上丘的视网膜传入纤维，可介导视觉与躯体感觉环路的门控分离，使出生时的感觉环路具备模态特异性。阻断I型视网膜波会导致躯体感觉与视觉环路在上丘的汇聚持续时间延长，进而对上丘的分子特征产生长期影响，并引发眼特异性分离缺陷与视网膜拓扑投射异常。综上，上丘通过将模态特异性刺激引导至对应的感觉通路，成为调控感觉环路发育的关键节点。
实验整体设计：于小鼠出生后第0~1天（P0-P1）向玻璃体腔内注射50 mM 甘珀酸（carbenoxolone, cbx, 默克, C4790）或生理盐水，在出生后第6天（P6）分离上丘的浅层与深层组织进行批量RNA测序（bulk RNA-seq）。实验采用显微解剖获取组织（每个样本混合3个小鼠脑组织），总RNA提取方法参照既往发表文献（Moreno-Juan等, 2017）。