Synaptic neurotransmitter depletion as a mechanism for the reduction of Parkinsonian beta oscillations during deep brain stimulation
Wednesday, Oct 17, 2012, 10:00 AM -11:00 AM
, A. ZIMNICK
, B. DOIRON
, R. TURNER
, J. RUBIN
Neurobio., Univ. of Pittsburgh, Pittsburgh, PA
Parkinson's disease (PD) is often associated with increased beta-band (10-15 Hz) oscillations in the subthalamic nucleus (STN) and globus pallidus (GPe and GPi). Several studies show that deep brain stimulation (DBS) in STN can reduce the amplitude of these oscillations in GP, suggesting that this reduction in beta power could partly explain the effectiveness of DBS in alleviating symptoms of PD. However, the mechanism by which DBS reduces beta oscillations is currently unknown.
Recent studies have begun to address this question by measuring firing rates and spectral properties of STN, GPe, and GPi activity before and during DBS stimulation. DBS simultaneously decreases STN firing rates significantly, and slightly increases GP rates in Parkinsonian non-human primates (1). This observation runs counter to intuition since GPe and GPi are each excited by STN. Furthermore, a majority of pallidal neurons exhibit post-stimulus spiking histograms consistent with synaptic activation entrained to the DBS signal (1). In addition, DBS reduces Parkinson's induced beta oscillations in GPi, leaves the spectral profile of STN activity largely unchanged, and virtually eliminates beta-frequency coherence between STN and GPi activity (2).
These observations may at first appear contradictory. How are STN firing rates decreased by DBS while the firing rates of their pallidal targets are simultaneously increased? How does DBS reduce GPi beta oscillations as well as STN-to-GPi coherence without changing the beta-band profile of STN activity? Using a computational model, we show that all of these observations are consistent with a depletion of neurotransmitter vesicles available to STN-to-GPi synapses caused by DBS induced axonal spikes in STN.
1. A. Moran, E. Stein, H. Tischler, K. Belelovsky, and I. Bar-Gad. Dynamic stereotypic responses of basal ganglia neurons to subthalamic nucleus high-frequency stimulation in the parkinsonian primate. Front Sys Neurosci, 5, 2011.
2. A. Moran, E. Stein, H. Tischler, and I. Bar-Gad. Decoupling neuronal oscillations during subthalamic nucleus stimulation in the Parkinsonian primate. Neurobiol of Disease, 2011.
DEEP BRAIN STIMULATION
NIH Grant 1R01NS070865-01A1
NSF Grant DMS-1021701
NSF Grant DMS-1121784
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.
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