Stinson Jeremiah P C, Brett Cooper A, Carroll Julianne B, Gabriele Mark L
Department of Biology, James Madison University, Harrisonburg, VA, United States.
Front Neuroanat. 2021 Mar 16;15:649478. doi: 10.3389/fnana.2021.649478. eCollection 2021.
Guidance errors and unrefined neural map configurations appear linked to certain neurodevelopmental conditions, including autism spectrum disorders. Deficits in specific multisensory tasks that require midbrain processing are highly predictive of cognitive and behavioral phenotypes associated with such syndromes. The lateral cortex of the inferior colliculus (LCIC) is a shell region of the mesencephalon that integrates converging information from multiple levels and modalities. Mature LCIC sensory maps are discretely-organized, mimicking its compartmental micro-organization. Intermittent modular domains receive patchy somatosensory connections, while inputs of auditory origin terminate in the encompassing extramodular matrix.Eph-ephrin signaling mechanisms instruct comparable topographic arrangements in a variety of other systems. Whether Eph-ephrin interactions also govern the assembly of LCIC multimodal maps remains unaddressed. Previously, we identified EphA4 and ephrin-B2 as key mediators, with overlapping expression patterns that align with emerging LCIC modules. Here, we implicate another member of this guidance family, ephrin-B3, and quantify its transient expression with respect to neurochemically-defined LCIC compartments. Multiple-labeling studies in GAD67-GFP knock-in mice reveal extramodular ephrin-B3 expression, complementary to that of EphA4 and ephrin-B2. This distinctive pattern sharpens over the early postnatal period (birth to P8), prior to ephrin-B3 downregulation once multimodal LCIC inputs are largely segregated (P12). Channel-specific sampling of LCIC ROIs show ephrin-B3 signal periodicities that are out-of-phase with glutamic acid decarboxylase (GAD;modular marker) signal fluctuations, and match calretinin (CR) waveforms (matrix marker). Taken together, the guidance mosaic registry with emerging LCIC compartments and its interfacing afferent streams suggest a prominent role for Eph-ephrins in ordering behaviorally significant multisensory midbrain networks.
引导错误和未成熟的神经图谱配置似乎与某些神经发育状况有关，包括自闭症谱系障碍。在需要中脑处理的特定多感官任务中的缺陷，高度预示着与此类综合征相关的认知和行为表型。下丘外侧皮质（LCIC）是中脑的一个壳层区域，整合来自多个层次和模态的汇聚信息。成熟的LCIC感觉图谱是离散组织的，模仿其分区微组织。间歇性模块化区域接收零散的躯体感觉连接，而听觉起源的输入终止于周围的模块外基质。Eph-ephrin信号机制在多种其他系统中指导类似的拓扑排列。Eph-ephrin相互作用是否也控制LCIC多模态图谱的组装仍未得到解决。此前，我们确定EphA4和ephrin-B2为关键介质，其重叠的表达模式与新兴的LCIC模块一致。在这里，我们指出这个引导家族的另一个成员ephrin-B3，并相对于神经化学定义的LCIC分区量化其瞬时表达。对GAD67-GFP基因敲入小鼠的多重标记研究揭示了模块外ephrin-B3的表达，与EphA4和ephrin-B2互补。这种独特的模式在出生后早期（出生至P8）会更加明显，在多模态LCIC输入基本分离（P12）后ephrin-B3会下调。对LCIC感兴趣区域的通道特异性采样显示，ephrin-B3信号的周期性与谷氨酸脱羧酶（GAD；模块化标记）信号波动不同步，且与钙视网膜蛋白（CR）波形（基质标记）匹配。综上所述，引导镶嵌与新兴的LCIC分区及其连接的传入信息流表明，Eph-ephrins在有序排列具有行为意义的多感官中脑网络中起着重要作用。
