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Yasin TEMEL"The role of 5-HT neurons in depressive-like behavior induced by high-frequency stimulation of the subthalamic nucleus".

Abstract :


The use of stimulation electrodes implanted in the brain to control severely disabling neurological and psychiatric conditions is an exciting and fast emerging area of clinical neuroscience.
As an example, high frequency stimulation (HFS) of the subthalamic nucleus (STN) has become the surgical therapy of choice for advanced Parkinson ’s disease (PD), and to date more than 30,000 PD patients worldwide have benefited from this procedure. Despite having important beneficial motor effects, bilateral STN HFS can be associated with the occurrence of unpleasant and debilitating psychiatric effects, including cognitive alterations, low mood, aggression, and impulsive acts and thoughts which are linked to suicide. These psychiatric effects can be a major burden to patients and their families, and often mitigate the positive effects on motor symptoms. In animals, HFS and other manipulations of the STN also produces a range of non-motor behavioural changes, including increased impulsivity and altered cognitive responses that appear to correlate with the adverse effects experienced by PD patients.
The author will discuss the potential mechanisms underlying these behavioural effects with special emphasis on the 5-hydroxytryptamine (5-HT: serotonin) system. In this respect, the author and co-workers recently found that HFS of the STN inhibits midbrain 5-HT neurons to evoke depression-related behavioural changes. Stimulation of the STN consistently inhibited the firing rate of 5-HT neurons in the dorsal raphe nucleus of the rat and evoked depressive-like behaviour in a widely used experimental paradigm of depression. Overall, these recent findings link reduced 5 HT function to the psychiatric effects of HFS of the STN observed in PD patients, and provide a rational basis for their clinical management. 

Selected publications

Temel Y, Visser-Vandewalle V, and Carpenter R. Saccadic latency during electrical stimulation of the human subthalamic nucleus. Current Biology (in press).
Temel Y, Boothman L, Blokland A, Magill P, Steinbusch HWM, Visser-Vandewalle V, Sharp T. Inhibition of 5-HT neuron activity and induction of depressive like behaviour by high frequency stimulation of the subthalamic nucleus. Proceedings of the National Academy of Sciences, 2007, 104(43):17087-17092.

Temel Y, Blokland A, Steinbusch HWM, Visser-Vandewalle V. The functional role of the subthalamic nucleus in the associative and limbic circuits. Progress in Neurobiology, 2005, 76(6):393-413.

Abdelhamid Benazzouz