Evolution of changes in neuronal activity in the subthalamic nucleus of rats with unilateral lesion of the substantia nigra assessed by metabolic andelectrophysiological measurements

Cellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functio nal changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was st abilized at a maximal level, In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analys ed by in situ hybridization the cellular expression of COI mRNA in the subt halamic neurons at different times, from 6 h to 14 days, after unilateral i ntranigral microinjection of 6-hydroxydopamine (6-OHDA) in rats. In paralle l, the time-dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthala mic neurons from 24 h after 6-OHDA intoxication, to 14 days (+26%). Similar ly, electrical activity started to increase slightly 24 h after lesion (+20 %) and remained significantly higher at 14 days after the lesion (+189%), C hanges in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperac tivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression sl ightly precede changes in electrical neuronal activity.