gms | German Medical Science

Objective: Bilateral 6-hydroxydopamine (6-OHDA) injections in the dorsolateral rodent striatum lead to retrograde degeneration of the motor associated nigrostriatal dopamine system and concomitant abnormal neuronal activity in the basal ganglia (BG) motor loop, which is used as model of Parkinson’s disease (PD). In the BG motor loop the subthalamic nucleus (STN) represents an important structure, which is often targeted for deep brain stimulation in PD patients. However, the STN also comprises areas of the BG associative and limbic loops. We were interested whether selective lesions of the dorsolateral striatum would differentially affect neuronal activity in the motor and associative-limbic parts of the rodent STN.

Methods: In male Spraque Dayley rats 6-OHDA (n=12) was bilaterally injected in the dorsolateral striatum in a stereotactic operation, sham-lesioned (n=10) rats received vehicle-injection. Four weeks later neuronal extracellular single-unit activity and local field potentials were recorded in the medial motor part and the lateral associative-limbic part of the STN in urethane (1.2 mg/kg) anaesthetized rats.

Results: 6-OHDA lesions of the dorsolateral striatum led to a significantly higher amount of bursting activity in the STN compared with sham-lesioned controls (p<0.05). In the lateral STN the burst activity was higher compared to the medial STN, which was, however, more pronounced in sham-lesioned rats. We also found significant differences in neuronal activity measures (discharge rate, mode of interspike intervals (ISI), skewness, kurtosis, maxApEn, coefficient of variation of ISI) between the medial and the lateral STN independent from the lesion. In addition, 6-OHDA lesions significantly raised the β-oscillatory activity of the local field potentials recorded in the medial and lateral STN.

Conclusions: 6-OHDA lesions of the dorsolateral striatum enhanced burst and β-oscillatory activity of the STN, which is similar to the findings in the STN of PD patients. However, these effects were largely independent from the lateral motor part or the medial associative part of the STN. This may be due to the fact that compared to primates in rats dendrites of STN neurons extend across almost the whole nucleus and axons form stronger intrinsic collaterals compared to primates. However, the differences in neuronal activity measures between the medial and lateral STN nevertheless indicate functional segregation of this nucleus.