The effect of striatal dopaminergic grafts on the neuronal activity in the substantia nigra pars reticulata and subthalamic nucleus in hemiparkinsonian rats | Zendy

Timothy P. Gilmour | Zendy; Brigitte Piallat | Zendy; Christopher A. Lieu | Zendy; Kala Venkiteswaran | Zendy; Renuka Ramachandra | Zendy; Anand N. Rao | Zendy; Andrew C. Petticoffer | Zendy; Michael Berk | Zendy; Thyagarajan Subramanian | Zendy

Open Access

The effect of striatal dopaminergic grafts on the neuronal activity in the substantia nigra pars reticulata and subthalamic nucleus in hemiparkinsonian rats

Author(s) -

Timothy P. Gilmour,

Brigitte Piallat,

Christopher A. Lieu,

Kala Venkiteswaran,

Renuka Ramachandra,

Anand N. Rao,

Andrew C. Petticoffer,

Michael Berk,

Thyagarajan Subramanian

Publication year - 2011

Publication title -

brain

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.142

H-Index - 336

eISSN - 1460-2156

pISSN - 0006-8950

DOI - 10.1093/brain/awr226

Subject(s) - subthalamic nucleus , basal ganglia , dopaminergic , neuroscience , substantia nigra , pars reticulata , transplantation , parkinsonism , parkinson's disease , local field potential , apomorphine , premovement neuronal activity , electrophysiology , dopamine , deep brain stimulation , biology , medicine , central nervous system , disease

The electrophysiological correlates of parkinsonism in the basal ganglia have been well studied in patients with Parkinson's disease and animal models. Separately, striatal dopaminergic cell transplantation has shown promise in ameliorating parkinsonian motor symptoms. However, the effect of dopaminergic grafts on basal ganglia electrophysiology has not thoroughly been investigated. In this study, we transplanted murine foetal ventral mesencephalic cells into rats rendered hemiparkinsonian by 6-hydroxydopamine injection. Three months after transplantation, extracellular and local field potential recordings were taken under urethane anaesthesia from the substantia nigra pars reticulata and subthalamic nucleus along with cortical electroencephalograms and were compared to recordings from normal and hemiparkinsonian controls. Recordings from cortical slow-wave activity and global activation states were analysed separately. Rats with histologically confirmed xenografts showed behavioural improvement measured by counting apomorphine-induced rotations and with the extended body axis test. Firing rates in both nuclei were not significantly different between control and grafted groups. However, burst firing patterns in both nuclei in the slow-wave activity state were significantly reduced (P < 0.05) in rats with large surviving grafts, compared to hemiparkinsonian controls. The neuronal firing entropies and oscillations in both nuclei were restored to normal levels in the large-graft group. Electroencephalogram spike-triggered averages also showed normalization in the slow-wave activity state (P < 0.05). These results suggest that local continuous dopaminergic stimulation exerts a normalizing effect on the downstream parkinsonian basal ganglia firing patterns. This novel finding is relevant to future preclinical and clinical investigations of cell transplantation and the development of next-generation therapies for Parkinson's disease that ameliorate pathophysiological neural activity and provide optimal recovery of function.

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