Selective connectivity of dopamine neurons projecting to the posterior striatum
Midbrain dopamine (DA) neurons play important roles in various brain functions, including motor control, motivation, and reinforcement learning. In Parkinson's disease (PD) midbrain DA neurons are progressively lost as the disease advances. Specifically, there is a prominent decay of dopaminergic axons in the posterior putamen and a corresponding loss of dopamine neurons in the ventrolateral SNpc. Here, Menegas and coworkers used a very complementary set of methods: rabies virus tracing, CLARITY, and light sheet microscopy to label subpopulations of DA neurons according to their projection sites and their monosynaptic inputs in mice. They found that almost all DA neurons received "clusters" of inputs originating within the ventral striatum. However, DA neurons whose target is the posterior striatum receive far fewer inputs from this area. Rather, they receive projections from other regions, such as the globus pallidus (GP) STN, and zona incerta. In addition, the inputs to DA neurons that project to the posterior striatum are shifted dorsolaterally compared to inputs to other DA subpopulations. This shift may be caused by a relatively low number of inputs from the ventral striatum and the large number of inputs from other regions (i.e. GP, entopeduncular nucleus, and STN) The investigators suggest that their findings may have practical implications regarding DBS of the STN in PD because this and other sites found to be effective in the treatment of PD send monosynaptic projections onto DA neurons projecting to the posterior putamen, thus having a more specific effect on the motor circuit. More important, however, these results support evidence that neurons projecting to the posterior striatum are unique and regulated by different inputs. Unlike other DA neurons that receive a prominent inhibitory expectation signal from the ventral striatum, those that project to the posterior striatum may facilitate encoding of more "stable values," compatible with a role for habitual, rather than goal directed, learning. This may provide a first approach to the still unanswered question of how DA subpopulations could be related to the variety of manifestations and the selective vulnerability of the SNpc ventrolateral tier in PD. Additionally, the methodology used by the investigators will facilitate similar anatomical studies in other brain areas in an efficient and quantitative manner.
Movement disorders official journal of the Movement Disorder Society