Targeting Cre Recombinase to Specific Neuron Populations with Bacterial Artificial Chromosome Constructs

Cre expression in forebrain circuits, with labeling of specific neuronal projection systems in the cerebral cortex (A, Etv1; B, Ntsr1) and striatum (C, Drd2; D, Drd1a). Expression is produced in layer 5 corticostriatal neurons in an Etv1 BAC-Cre line (A, Etv1). Cre is expressed in layer 6 corticothalamic neurons in an ntsr1 BAC-Cre line (B, Ntsr1). Clearly labeled are the projection axons of these neurons, which terminate in the dorsal thalamic nuclei. In the striatum, the majority of neurons are medium spiny projection neurons, which are evenly divided into striatopallidal (indirect pathway) and striatonigral (direct pathway) neurons, which selectively express the drd2 and drd1a dopamine receptors, respectively. Cre expression produced in Drd2 BAC-Cre lines (C, Drd2) is directed to striatopallidal neurons. In this line, labeled neurons in the striatum extend axons that terminate in the globus pallidus external segment (GPe). In contrast, expression produced in Drd1a BAC-Cre lines (D, Drd1a) is directed to striatonigral neurons, which have axons that extend through the globus pallidus to terminate in the internal segment of the globus pallidus (GPi) and substantia nigra (not shown).