Subthalamic nucleus activity in the awake hemiparkinsonian rat: Relationships with motor and cognitive networks

Abstract

Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson’s disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronizedSTNlocal field potential (LFP) activity with activity in motor cortex(MCx)andmedial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases inSTNandMCx29–36HzLFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings frommPFC3 weeks after dopamine depletion failed to show peaks in 29–36 Hz LFP power. However, mPFC and STN both showed peaks in the 45–55 Hz frequency range in LFP powerandcoherence during walking beforeand21 days afterdopaminedepletion. Interestingly,powerin this lowgammarangewastransiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45–55 Hz activity, the amplitude of the exaggerated 29–36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system.