Effects of 6-hydroxydopamine-induced severe or partial lesion of the nigrostriatal pathway on the neuronal activity of pallido-subthalamic network in the rat
Experimental Neurology. 2007-05-01; 205(1): 36-47
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1. Exp Neurol. 2007 May;205(1):36-47. doi: 10.1016/j.expneurol.2006.12.016. Epub
2006 Dec 29.
Effects of 6-hydroxydopamine-induced severe or partial lesion of the
nigrostriatal pathway on the neuronal activity of pallido-subthalamic network in
Breit S(1), Bouali-Benazzouz R, Popa RC, Gasser T, Benabid AL, Benazzouz A.
(1)INSERM U.318, Department of Preclinical Neurobiology, Joseph Fourier
University, Grenoble, France.
The origin of changes in the neuronal activity of the globus pallidus (GP) and
the subthalamic nucleus (STN) in animal models of Parkinson’s disease (PD) is
still controversial. The aim of the study was to investigate the neuronal
activity of STN and GP neurons under urethane anesthesia in an early and in an
advanced stage PD rat model. 6-Hydroxydopamine (6-OHDA) injection into the
striatum induced a partial lesion of dopamine cells in the substantia nigra pars
compacta (SNc) and fibers in the striatum. The GP firing rate decreased
significantly with no significant change of the pattern. 6-OHDA injection into
the SNc induced a total or subtotal lesion without any change in the firing rate
and patterns of GP neurons. Concerning the STN, after partial lesion, the firing
rate remained unchanged but the firing pattern significantly changed towards a
more irregular and bursty pattern. In rats with total or subtotal lesion of the
SNc the firing rate increased significantly and the relative amount of tonic
neurons significantly decreased. Our results demonstrate that neuronal
reactivity in the basal ganglia network considerably differs in the early versus
late stage model of PD. We showed that the pathological activity of STN neurons
after severe lesion is not mediated by the GP. Moreover, the unchanged activity
of GP neurons is likely to be a consequence of the STN hyperactivity. These data
suggest that in the GP-STN-GP network, the excitatory influence of the STN-GP
pathway overrides that of the GABAergic GP-STN pathway, questioning the
classical model of basal ganglia organization.
PMID: 17395181 [Indexed for MEDLINE]