Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models

Movement, cognition, emotion, and positive reinforcement are influenced by mesostriatal, mesocortical, and mesolimbic dopamine systems. We describe a fourth major pathway originating from mesencephalic dopamine neurons: a mes othalamic system. The dopamine transporter, specific to dopamine containing axons, was histochemically visualized in thalamic motor and limbic-related nuclei and regions that modulate behavioral state as opposed to sensory nu clei in rats, nonhuman primates, and humans. Anatomical tracing established this innervation's origin via axon collaterals from the mesostriatal pathw ay. These findings implicate the thalamus as a novel site for disease speci fic alterations in dopamine neurotransmission, such as exist with nigral. d egeneration attending Parkinson's disease. This was confirmed in hemiparkin sonian animals where reduction of thalamic dopamine innervation occurred co incident with signs of active axonal degeneration. Individual mesencephalic dopamine neurons therefore have the potential to modulate normal and patho logic behavior not only through traditional nigrostriatal. pathways but als o by way of axon collaterals that innervate the thalamus.