Sparse and combinatorial neuron labelling

Sparse, random labelling of individual cells is a key approach to study brain circuit organisation and development. An array of methods based on genetic engineering now complements older methods such as Golgi staining, facilitating analysis while providing higher information content. Increasingly refined expression strategies based on transcriptional modulators and site-specific recombinases are used to distribute markers or combinations of markers within specific neuronal subsets. Several trends are emerging: first, increasing labelling density with multiplexed markers to allow more cells to be reliably distinguished; second, using labels to report lineage relationships among defined cells in addition to anatomy; third, coupling cell labelling with genetic manipulations that reveal or perturb cell function. These strategies offer new opportunities for characterizing the fine scale architecture of neuronal circuits, and understanding lineage and functional relations among their cellular components in normal or experimental situations.

► Sparse and stochastic labelling approaches provide access to individual neuron anatomy. ► Hybrid genetic strategies use recombination to stochastically distribute markers within genetically defined populations. ► In Brainbow transgenes, multiple recombinations randomise expression of multiple markers or marker combinations. ► Interchromosomal recombination strategies can mark sister cells with two colours that also code their genotype.