2P-NucTag: On-demand phototagging for molecular analysis of functionally identified cortical neurons.

2P-NucTag enables stable, on-demand labeling of functionally identified cortical neurons, revealing unexpected gene expression differences in hippocampal cells of behaving mice.

• Why it matters: Understanding how genetic and physiological properties link in neural circuits is crucial for decoding brain function, but mapping molecular traits onto specific neuron types in vivo remains difficult.
• What they did: The authors developed a high-throughput two-photon nuclear phototagging (2P-NucTag) method that labels single neurons after functional testing, allowing transcriptional profiling and downstream experiments in live animals.
• The result: This approach uncovers novel molecular distinctions among hippocampal neurons and facilitates diverse analyses like electrophysiology and histology, advancing insights into neural circuit organization.