ibRV Reveals Unprecedented Detail in Brain Circuit Development

The intricate networks of neurons in our brains, known as circuits, are fundamental to diverse brain functions. When these circuits fail to develop correctly, it is associated with neurodevelopmental disorders. Despite their importance, scientists have an incomplete understanding of how specific brain circuits form and how diseases impact them, largely due to a lack of methods that can study them at both scale and single-cell resolution. Existing "gold standard" techniques like monosynaptic rabies tracing are hampered by issues such as cellular toxicity, low throughput, lack of control over the timing of labeling, and the inability to access individual neuron's molecular profiles.

To overcome these challenges, researchers have developed an innovative new tool: the inducible barcoded rabies virus (ibRV). This novel approach enables temporal-controlled labeling of synaptic circuits, followed by high-throughput single-cell genomics readout. As lead author Zhang notes in the paper, "ibRV allows for dissecting neuronal circuit changes over time at single-cell and spatial resolution."

The utility of ibRV was demonstrated by applying it to study the development of specific mouse cortical circuits. The team focused on late prenatal and postnatal stages, using single-cell genomics and unbiased spatial transcriptomics as readouts. Through this application, they characterized and quantified developmental connectivity patterns and molecular cascades that underlie their formation. Additionally, they constructed functional in silico circuit models that enable interrogation of circuit function and dysfunction at specific developmental stages.

This study provides novel tools for circuit analysis. The insights gained from using ibRV can provide new insights into the mechanisms of mammalian brain development.