QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 2, 2006, 26(31):8101-8114; doi:10.1523/JNEUROSCI.5140-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Heimer, G. Articles by Bergman, H. Search for Related Content PubMed PubMed Citation Articles by Heimer, G. Articles by Bergman, H.

 Previous Article  |  Next Article 

Neurobiology of Disease
Dopamine Replacement Therapy Does Not Restore the Full Spectrum of Normal Pallidal Activity in the 1-Methyl-4-Phenyl-1,2,3,6-Tetra-Hydropyridine Primate Model of Parkinsonism

Gali Heimer,^1,4 Michal Rivlin-Etzion,^1,2 Izhar Bar-Gad,⁵ Joshua A. Goldberg,⁶ Suzanne N. Haber,⁷ and Hagai Bergman^1,2,3

¹Department of Physiology, ²Interdisciplinary Center for Neural Computation, and ³Eric Roland Center for Neurodegenerative Diseases, The Hebrew University–Hadassah Medical School, Jerusalem, Israel, 91120, ⁴Department of Pediatrics, Hadassah–Hebrew University Medical Center, Jerusalem, Israel, 91120, ⁵Gonda Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel, 52900, ⁶Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, and ⁷Department of Pharmacology and Physiology, University of Rochester, Rochester, New York 14642

Correspondence should be addressed to Gali Heimer, Department of Physiology, The Hebrew University–Hadassah Medical School, P.O. Box 12272, Jerusalem, Israel 91120. Email: galih{at}md.huji.ac.il

Current physiological studies emphasize the role of neuronal oscillations and synchronization in the pathophysiology of Parkinson’s disease; however, little is known about their specific roles in the neuronal substrate of dopamine replacement therapy (DRT). We investigated oscillatory activity and correlations throughout the different states of levodopa-naive parkinsonism as well as "Off–On" and dyskinetic states of DRT in the external globus pallidum (GPe) of tremulous (vervet) and rigid-akinetic (macaque) monkeys and in the internal globus pallidum (GPi) of the vervet monkey. We found that, although oscillatory activity of cells and interneuronal correlation in both pallidal segments increases after induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and decreases in response to DRT, important differences exist between the two pallidal segments. In the GPi, the fraction of oscillatory cells and relative power of oscillations were significantly higher than in the GPe, and the dominant frequency was within the range of 7.5–13.5 Hz compared with a range of 4.5–7.5 Hz within the GPe. The interneuronal correlations were mostly oscillatory in the GPi, whereas at least half are non-oscillatory in the GPe. We demonstrate that the tremor characteristics after exposure to DRT do not resemble those of the normal or the levodopa-naive state. Moreover, although DRT reverses the MPTP-induced neuronal changes (rate, pattern, and pairwise correlations), the balance between GPe and GPi fails to restore. We therefore suggest that this imbalance reflects additional abnormal organization of the basal ganglia networks in response to dopamine replacement and may constitute the physiological substrate of the limitations and side effects of chronic DRT.

Key words: Parkinson’s disease; basal ganglia; MPTP; tremor; cross-correlations; levodopa

---

Received May 2, 2005; revised June 9, 2006; accepted June 10, 2006.

Correspondence should be addressed to Gali Heimer, Department of Physiology, The Hebrew University–Hadassah Medical School, P.O. Box 12272, Jerusalem, Israel 91120. Email: galih{at}md.huji.ac.il

This article has been cited by other articles:

				C. Dejean, B. Hyland, and G. Arbuthnott Cortical Effects of Subthalamic Stimulation Correlate with Behavioral Recovery from Dopamine Antagonist Induced Akinesia Cereb Cortex, May 1, 2009; 19(5): 1055 - 1063. [Abstract] [Full Text] [PDF]

				S. Elias, Y. Ritov, and H. Bergman Balance of Increases and Decreases in Firing Rate of the Spontaneous Activity of Basal Ganglia High-Frequency Discharge Neurons J Neurophysiol, December 1, 2008; 100(6): 3086 - 3104. [Abstract] [Full Text] [PDF]

				L. Liang, M. R. DeLong, and S. M. Papa Inversion of Dopamine Responses in Striatal Medium Spiny Neurons and Involuntary Movements J. Neurosci., July 23, 2008; 28(30): 7537 - 7547. [Abstract] [Full Text] [PDF]

				M. Rivlin-Etzion, O. Marmor, G. Saban, B. Rosin, S. N. Haber, E. Vaadia, Y. Prut, and H. Bergman Low-Pass Filter Properties of Basal Ganglia Cortical Muscle Loops in the Normal and MPTP Primate Model of Parkinsonism J. Neurosci., January 16, 2008; 28(3): 633 - 649. [Abstract] [Full Text] [PDF]

				Y. Niv and M. Rivlin-Etzion Parkinson's Disease: Fighting the Will? J. Neurosci., October 31, 2007; 27(44): 11777 - 11779. [Full Text] [PDF]

				C. R. Lee and J. M. Tepper A Calcium-Activated Nonselective Cation Conductance Underlies the Plateau Potential in Rat Substantia Nigra GABAergic Neurons J. Neurosci., June 13, 2007; 27(24): 6531 - 6541. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help