The thalamus occupies a pivotal position within the cortico-basal ganglia-cortical circuits. In Parkinson's disease, the thalamus exhibits pathological neuronal discharge patterns, foremost increased bursting and oscillatory activity, which are thought to perturb the faithful transfer of basal ganglia impulse flow to the cortex. Analogous abnormal thalamic discharge patterns develop in animals with experimentally reduced thalamic noradrenaline; conversely, added to thalamic neuronal preparations, noradrenaline exhibits marked anti-oscillatory and anti-bursting activity. Our study is based on this experimentally established link between noradrenaline and the quality of thalamic neuronal discharges.

We analysed fourteen thalamic nuclei from all functionally relevant territories of nine patients with Parkinson's disease and eight controls and measured noradrenaline with high pressure liquid chromatography with electrochemical detection.

In Parkinson's disease, noradrenaline was profoundly reduced in all nuclei of the motor (pallidonigral and cerebellar) thalamus (ventroanterior: -86%, p=0.0011; ventrolateral oral: -87%, p=0.0010; ventrolateral caudal: -89%, p=0.0014): Also marked noradrenaline losses, ranging from 68% to 91% of controls, were found in other thalamic territories, including associative, limbic and intralaminar regions; the primary sensory regions were only mildly affected.

The marked noradrenergic deafferentiation of the thalamus discloses a strategically located noradrenergic component in the overall pathophysiology of the Parkinson's disease, suggesting a role in the complex mechanisms involved with the genesis of the motor and non-motor symptoms. Our study thus significantly contributes to the knowledge of the extrastriatal non-dopaminergic mechanisms of Parkinson's disease with direct relevance to treatment of this disorder.