tracttracing

Tract tracing, in neuroscience, refers to a set of techniques for mapping neuronal connections by labeling axons and their terminals, revealing projections between brain regions. Tracers can be classified as anterograde or retrograde. Anterograde tracers move from neuronal cell bodies toward axon terminals, revealing efferent projections; retrograde tracers do the opposite, labeling neurons that project to the injection site.

Conventional tracers include fluorescent dyes and biotinylated compounds. Examples: Phaseolus vulgaris leucoagglutinin (PHA-L) and biotinylated dextran amine (BDA) for anterograde labeling; cholera toxin subunit B (CTB) and Fluoro-Gold for retrograde labeling. These are typically transported within monosynaptic connections and detected with histology and microscopy after a survival period.

Viral tracers offer trans-synaptic capabilities and cell-type specificity. Pseudorabies virus (PRV), herpes simplex virus (HSV), and rabies virus can spread across synapses, enabling mapping of multi-synaptic circuits; monosynaptic rabies tracing uses a genetically modified rabies strain that spreads only to direct inputs from starter neurons. Adeno-associated viruses (AAVs) can be used for stable, non-trans-synaptic labeling; when paired with cre-lox systems, they achieve selective labeling of specific neuronal populations.

In practice, tract tracing requires precise stereotaxic injections, appropriate biosafety considerations, and careful experimental design. The labeling is followed by histological processing and imaging, sometimes including tissue clearing for 3D reconstruction.

Limitations include incomplete uptake, variable transport rates, potential toxicity (notably with viral tracers), and difficulty inferring functional connectivity or synaptic strength. Tract tracing remains a foundational tool in anatomy and neuroscience for delineating brain networks and circuit architecture.