These abnormal firing patterns across the CxFn were effectively eliminated by STN-DBS. The simultaneous recording of spikes and LFP by the same recording channel also allowed us to study the coherence between them. The results showed that there was increased coherence level between spikes and local field potentials at beta band only in the 6-OHDA-lesioned hemisphere.

The significance of the increased coherence is unclear, but may contribute to bradykinesia and other movement suppression (Brown and Williams, 2005). Beta-band spike-field coherence may also represent excessive “stop” signals that underlie akinesia in PD (Swann et al., 2011). In this study, we also provided direct evidence of the occurrence of antidromic spikes in MI during the DBS paradigm. This finding Wnt antagonist supports previous studies using electroencephalogram (EEG) recordings

that STN-DBS results in the antidromic activation of motor cortex (Dejean et al., 2009; Li et al., 2007). In these studies, evoked wave in the EEG was correlated to the positive behavioral effects. In a recent study (Gradinaru et al., 2009), it was found that, while optogenetic stimulation of excitatory nerve terminals within STN was beneficial in improving Parkinsonian motor symptoms, optical inhibition or excitation confined to STN neurons was ineffective, learn more raising the possibility that antidromic activation of the cortico-STN pathway underlies the therapeutic

Phosphoprotein phosphatase mechanism. Our finding that the peak antidromic frequency generated coincided with the optimal effect of STN-DBS also supports this hypothesis. More importantly, we showed that an antidromic spike had a strong effect on the firing probability of the neuron immediately following it, and the increased mean firing rate during DBS was primarily the effect of antidromic spikes. Our results therefore provide the neurobiological basis of the recent findings that highlight the importance of cortex in mediating beneficial effect of STN-DBS. For example, by using the recorded activity to drive the stimulation, Rosin et al. (2011) showed that short trains of stimulation pulses were effective only if they were triggered from cortical activity, but not from the basal ganglia. Mure et al. (2012) showed that, in PD patients, the improved sequence learning with STN-DBS, but not with L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, was associated with increases in activity in supplementary and premotor cortices. In human PD patients, DBS of the internal globus pallidus (GPi) is also effective in alleviating Parkinsonian symptoms (Weaver et al., 2012). Whether a similar antidromic activation of the known cortex-GPi projection (Naito and Kita, 1994) contributes to the therapeutic effect of GPi-DBS remains to be studied.