A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Postnatal brain development relies on sensory experience to refine neural circuits.
• Molecular mechanisms, particularly sensory-induced gene expression, are crucial but not fully understood.
• Characterizing developmental gene programs responsive to sensory input is essential for understanding circuit maturation.

Purpose of the Study:

• To comprehensively map the transcriptional responses of individual cell types in the developing mouse visual cortex to sensory experience.
• To identify specific genes and molecular pathways regulated by sensory deprivation and stimulation during a critical developmental period.
• To provide a valuable single-nucleus RNA sequencing dataset for future research on sensory-guided neural circuit development.

Main Methods:

• Single-nucleus RNA sequencing of 118,529 nuclei from mouse visual cortex.
• Isolation of sixteen distinct neuronal and non-neuronal cell types.
• Analysis of transcriptional changes in response to sensory deprivation and stimulation using RNA velocity and CellChat.

Main Results:

• Identification of 1,268 unique sensory-induced genes in the developing brain.
• Differential gene expression patterns observed across various cortical cell types, with excitatory neurons (especially layer 2/3 pyramidal neurons) showing high sensitivity.
• Discovery of Neurexin and Neuregulin signaling networks involved in cell-cell interactions.
• Evidence that sensory-induced genes in excitatory neurons promote synapse-to-nucleus communication via enhanced kinase activity.

Conclusions:

• Sensory experience profoundly influences gene expression programs in specific cell types within the developing visual cortex.
• The identified sensory-induced genes and signaling pathways offer novel insights into the molecular basis of experience-dependent neural circuit refinement.
• This dataset serves as a critical resource for dissecting the mechanisms by which sensory input shapes brain wiring during development.