Developmental Speed of Species-Specific Thalamocortical Synchronization

Developmental timing in brain formation has traditionally been studied independently across regions; however, spatial and temporal synchronization between regions is essential for the formation of functional neural circuits. In humans, the cerebral cortex develops slower, allowing for the formation of complex circuits that enhance cognitive abilities. Yet, not all brain regions follow the same developmental pace. The thalamocortical system, in particular, shows accelerated synchronization in humans, with thalamic connections reaching the subplate and cerebral cortex at early neurogenic phases. This early synchronization suggests a unique human specialization that remains largely unexplored. Such divergence may offer an extended window for distinct specializations to arise, facilitating cellular diversity and complex circuit formation, key drivers of evolutionary advantage. This raises the intriguing possibility that the thalamus, a subcortical structure, plays a critical role in driving novel specializations within the human subplate and cortex earlier than thought. Here, I aim to uncover the fundamental principles governing species-specific synchronization and developmental timing in the thalamocortical system, and their impact on human brain development. To achieve this, we will generate novel human stem cell-derived models replicating the self-emerging properties of thalamic-subplate communication. By employing multi-omic comparative approaches, we will investigate human-specific specializations and diversification of subplate dynamics, while exploring the consequences of disrupted synchronization in human and mouse models. In sum, our work will reveal the molecular and cellular consequences of accelerated thalamic-subplate synchronization in human development. This project could establish a link between altered time dynamics and neurodevelopmental disorders, offering a fresh perspective on the critical role of precise synchronization in human brain development.