Introduction: The motor symptoms of Parkinson's disease (PD) present with pathological neuronal activity in the basal ganglia. Although neuronal firing rate changes in the globus pallidus internus (GPi) and externus (GPe) are reported to underlie the development of PD motor signs, firing rates change inconsistently, vary confoundingly with some therapies, and are poor indicators of symptom severity. Methods: We explored the relationship between parkinsonian symptom severity and the effectiveness with which pallidal neurons transmit information. We quantify neuronal entropy and information - alternatives to firing rate and correlations respectively - in and between GPe and GPi neurons using a progressive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, non-human primate model of PD. Results: Neuronal entropy and symptom severity were not linearly correlated: in both pallidal segments, entropy increased from naive to moderate parkinsonism, but decreased with further progression to the severely parkinsonian condition. In contrast, information transmitted from GPe to GPi increased consistently with symptom severity. Furthermore, antidromic information from GPi to GPe increased substantially with symptom severity. Together, these findings suggest that as parkinsonian severity increases, more and more information enters GPe and GPi from common sources, diminishing the relative importance of the orthodromic GPe to GPi connection. Conclusions: With parkinsonian progression, the direct and indirect pathways lose their independence and start to convey redundant information. We hypothesize that a loss of parallel processing impairs the ability of the network to select and implement motor commands, thus promoting the hypokinetic symptoms of PD.
Bibliographical noteFunding Information:
This work was supported by funding from the National Institutes of Health , NINDS-R01-058945 (J.L.V.) and NINDS-R01-037019 (J.L.V.); the National Science Foundation , CBET-CAREER-1351112 (A.D.D.); and a post-doctoral fellowship from the Parkinson's Disease Foundation (A.M.). The authors declare no competing financial interests.
© 2015 Elsevier Ltd.
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- Basal ganglia
- Globus pallidus
- Neural information
- Parkinson's disease