9% ± 2.0% of time mobile (p < 0.001 compared with DBS off; p < 0.05 compared with intact) and 17.8% ± 1.4% freezing (p < 0.001 compared

with DBS off; p < 0.05 compared with intact). These beneficial effects disappeared immediately when STN-DBS was turned off. Bradykinesia symptoms, as reflected by decreased fine movement and reduced mobile speed, were also evident in the lesioned animals and were similarly alleviated during the delivery of STN-DBS (Figure 1D). Furthermore, in the classical apomorphine-induced contralateral rotation test, STN-DBS resulted in a modest but statistically significant reduction of see more the rotation speed, which was measured as the number of turns per min (pre-DBS: 19.08 ± 0.61/min; DBS: 16.62 ± 0.62/min; p < 0.01, post-DBS: 18.12 ± 0.73/min; n = 26, Figure 1E). We also characterized the dependence of the therapeutic effect of the STN-DBS paradigm on the stimulation frequency and pulse width. As

summarized in Figure 1F, at constant stimulus width PI3K inhibitor of 60 μs, low frequency (0.2–10 Hz) STN-DBS failed to alleviate the motor deficit of the hemi-Parkinsonian animals. However, when the stimulus frequency was 50 Hz and up to 200 Hz, significant improvement was seen in the percentage of time spent in motion. Among the four effective stimulation frequencies tested, namely 50, 125, 200, and 250 Hz, the optimal frequency was 125 Hz, which is in line with those used in clinical and experimental studies. The efficacy of the DBS appeared to be less dependent on pulse width. As shown in Figure 1G, at a constant stimulation frequency of 125 Hz, significant therapeutic effects could be achieved at pulse width ranging Levetiracetam from 20 to 80 μs. The falling off of efficacy at 100 μs suggested that the likely target of the stimulation is fibers rather than cells. We recorded extracellular neuronal activities from the MI layer V neurons in both intact and 6-OHDA lesioned rats via multichannel recording

arrays when the animals were awake and freely moving. Neuronal activities recorded by each channel were sorted into single units based on the electrophysiological characteristics of spike waveforms in the principal component space (Figure S2A). Two major classes of neuronal unit could be identified. One type of neuron exhibited a relatively long spike width (∼0.5–0.8 ms) and low spontaneous firing rate (<10 Hz), which were presumed to be pyramidal, projection neurons (PNs). Compared with the PNs, presumed interneurons (INs) held shorter spike width (∼0.2–0.5 ms), but higher spontaneous firing rate (∼8–45 Hz). Based on the correlation of the firing rate and spike width (Figure S2B), these two classes of neurons could be distinguished unambiguously. The STN is one of the innervation targets of the long-range corticofugal axons (Kita and Kita, 2012).