THE THALAMOSTRIATAL SYSTEM: A TARGET FOR TOURETTE SYNDROME SURGERY?

Emory University, Atlanta GA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to elucidate the electrophysiological effects of stimulation of the centromedian nucleus (CM) of the thalamus upon striatal neurons. The rationale supporting this series of experiments is twofolds. First, despite the strong anatomical evidence for the existence of a major glutamatergic CM-striatal projection, very little is known about the physiology of the thalamostriatal pathways. Second, there is empirical evidence that deep brain stimulation of CM alleviates some of the symptoms in Parkinson's disease and reduces dramatically tics in patients who suffer of Tourette syndrome. However, because of our limited knowledge of the thalamostriatal system, these clinical observations remain purely empirical and do not rely on any solid functional basis, which limits considerably their refinement and deeper understanding of their underlying physiological mechanisms. Over the past year, the responses of hundreds of striatal cells were recorded following burst stimulation of CM. The CM stimulation with trains of stimuli at high frequency (100 Hz, 100 pulses/train) had an effect in the majority of recorded cells, which responded with either excitatory or inhibitory responses. Overall, the majority of putamenal projection cells and interneurons responded to thalamic stimulation by complex changes of activity composed of long latency excitatory and inhibitory effects suggesting the involvement of the intrinsic striatal GABaergic and cholinergic microcircuitry. Together, findings of this study provide evidence for complex physiological effects of thalamic inputs upon striatal neurons. These data are highly significant and help to understand the role of the thalamostriatal system in the functional circuitry of the basal ganglia. They also provide solid data to further understand the neural mechanisms that may underlie the beneficial effects of CM deep brain stimulation in PD and/or Tourette syndrome.