Evolution of the basal ganglia: dual-output pathways conserved throughout vertebrate phylogeny

The basal ganglia, including the striatum, globus pallidus interna and externa (GPe), subthalamic nucleus (STN), and substantia nigra pars compacta, are conserved throughout vertebrate phylogeny and have been suggested to form a common vertebrate mechanism for action selection. In mammals, this circuitry is further elaborated by the presence of a dual-output nucleus, the substantia nigra pars reticulata (SNr), and the presence of modulatory input from the cholinergic pedunculopontine nucleus (PPN). We sought to determine whether these additional components of the mammalian basal ganglia are also present in one of the phylogenetically oldest vertebrates, the lamprey. We show, by using immunohistochemistry, tract tracing, and whole-cell recordings, that homologs of the SNr and PPN are present in the lamprey. Thus the SNr receives direct projections from inwardly rectifying γ-aminobutyric acid (GABA)-ergic striatal neurons expressing substance P, but it is also influenced by indirect basal ganglia projections from the STN and potentially the GPe. Moreover, GABAergic SNr projection neurons are tonically active and project to the thalamus and brainstem motor areas. The homolog of the PPN contains both cholinergic and GABAergic neurons and is connected with all the nuclei of the basal ganglia, supporting its proposed role as part of an extended basal ganglia. A separate group of cholinergic neurons dorsal to the PPN corresponds to the descending mesencephalic locomotor region. Our results suggest that dual-output nuclei are part of the ancestral basal ganglia and that the PPN appears to have coevolved as part of a mechanism for action selection common to all vertebrates.