Functional activity of zona incerta neurons is altered after nigrostriatal denervation in hemiparkinsonian rats.
The cellular expression of cytochrome oxidase subunit I (COI) mRNA as a metabolic marker for neuronal activity has recently been used to examine the effects of nigrostriatal denervation on the functioning of the basal ganglia. However, this technique also allows functional changes to be detected in other cerebral structures in parkinsonian syndromes. Since the zona incerta has been implicated in locomotor activity and has been the site of stereotactic surgery in Parkinson's disease, the aim of our study was to determine whether changes in neuronal activity are observed in this structure during parkinsonism. Using in situ hybridization, we analyzed the expression of COI mRNA in rats with 6-hydroxydopamine unilateral lesion of the substantia nigra and sham-operated animals. A quantitative analysis showed that COI mRNA expression was increased in the zona incerta ipsilateral to the lesion 24 h and 3 days after lesion, but by day 14 had returned almost to the level observed in controls. The hyperactivity of zona incerta neurons was confirmed by single-unit electrophysiological recordings. In contrast to the COI mRNA expression, the increase in electric neuronal activity was still observed 1 month after the lesion. This increase in zona incerta neuronal activity after nigrostriatal denervation might be related to the pathophysiology of parkinsonism, at least in the early stages, in agreement with previous reports suggesting an involvement of the zona incerta in motor functions.
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INSERM U 289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, Paris, 75013, France.
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Féger
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D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D003342:Corpus Striatum / Q000166:cytology*; D003714:Denervation; D050483:Dopamine Plasma Membrane Transport Proteins; D003576:Electron Transport Complex IV / Q000235:genetics*; D004594:Electrophysiology; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000737:chemistry / Q000201:enzymology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology*; D013565:Sympatholytics
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D013565:Sympatholytics; D016627:Oxidopamine; D003576:Electron Transport Complex IV