A new pathway to pathology?

It’s not every day that a new anatomical pathway is discovered, so the recent finding that the primate thalamus receives dopaminergic inputs from various brain regions was bound to be greeted with interest. This robust and complex dopaminergic system could explain thalamic abnormalities that have been reported in conditions such as schizophrenia and Parkinson’s disease.

Nature Reviews Neuroscience 6, 665-669 (2005); doi:10.1038/nrn1753

Despite the fact that dopamine was detected in the thalamus of primates more than 20 years ago, the idea that this structure receives a significant dopamine innervation has not been acknowledged, perhaps because the rodent thalamus appears to receive only scant dopaminergic inputs.

Sánchez-González and colleagues looked for dopaminergic axons in the thalamic nuclei of adult humans and macaque monkeys using antibodies against tyrosine hydroxylase, dopamine and the dopamine transporter, DAT. They found that dopaminergic axons profusely target the thalamus, and that this innervation is particularly prominent in specific association, limbic and motor thalamic nuclei. Interestingly, the DAT content of dopaminergic axons varies across the thalamus, which suggests that dopaminergic signalling is more spatially and temporally restricted in some thalamic regions than in others.

(Image) Dopaminergic projections to the thalamus. Inputs from groups A8–A11 express the dopamine transporter, DAT, whereas those from groups A12–A15 and the lateral parabrachial nucleus express little or no DAT. Image courtesy of C. Cavada, Departamento de Anatomía, Histología y Neurociencia, Universidad Autonoma de Madrid, Spain.

Using retrograde tract tracing combined with immunohistochemistry, the researchers showed that dopamine innervation of the thalamus originates bilaterally in several dopaminergic neuronal populations, including those of the hypothalamus, the periaqueductal grey and the ventral mesencephalon.

The thalamus relays information to the neocortex from subcortical centres and from other cortical areas. This relay function is modulated such that the flow of information reflects the wakefulness of the animal and current attentional and behavioural demands. The finding of a widespread thalamic dopaminergic system leads to the inevitable conclusion that dopamine can modulate thalamic information transfer according to a range of environmental and internal signals. A closer inspection of this system could further our understanding of the dopamine-related disorders schizophrenia and Parkinson’s disease.

References and links

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ORIGINAL RESEARCH PAPER

Sánchez-González, M. A. et al. The primate thalamus is a key target for brain dopamine. J. Neurosci. 25, 6076−6083 (2005) | Article | PubMed |