Second, frequency following is also dependent on the degree of myelination of the axons (Chomiak and Hu, 2007; Richardson et al., 2000). As far as we know, although the corticofugal fibers are myelinated and fast conducting, most of the

projection to the subthalamic nucleus are minor collaterals of corticofugal fibers and are of unmyelinated type (Afsharpour, 1985; Debanne et al., 2011). Hence, the branch points of buy SAHA HDAC the collaterals could serve as low-pass filter and increase the difficulty of antidromic invasion. Also, as mentioned before, recruitment of inhibitory cortical interneurons may contribute to failure of frequency following. In conclusion, this study provided evidence that STN-DBS antidromically activates the layer V corticofugal projection neurons in the MI, which contributes to the disruption of abnormal neural activities in the MI in PD. The unpredictable nature of antidromic spikes may hold the key to the process, a hypothesis that needs to be verified. Two groups of adult male Sprague Dawley rats weighing 250–280 g were used, including 17 intact and 30 hemi-Parkinsonian

rats. All animal handling, surgical, and behavior testing procedures were carried out in accordance Sunitinib datasheet with university guidelines on animal ethics. A hemi-Parkinsonian rat was generated by unilateral injection of 6-OHDA into medial forebrain bundle (0.9% saline vehicle injection into the other side, named as unlesioned). After two weeks’ recovery, contralateral rotation behavior was tested for 15 min after subcutaneous injection of apomorphine (0.5 mg/kg) and those that rotated at least 15 cycles/min were selected for electrode implantation. Two pairs of stimulating electrodes (STABLOHM 675, CA Fine Wire, Grover Beach, CA) were implanted into bilateral STN (unilateral in intact rats), targeting at the dorsal-lateral portion of the nucleus, which is known to receive motor input mainly from the MI and is the site

of stimulation that generates the best motor improvement (Greenhouse et al., 2011; Romanelli et al., 2004). Contralateral muscle contraction at low threshold stimulation was indicative of the possibility that the electrode was very near or inserted into the internal capsule and therefore PD184352 (CI-1040) rejected for further experimentations. To monitor the extracellular neuronal activities in the layer V of MI, two multichannel microwire electrode arrays, each constructed of 16 stainless steel microwires (Plexon, Dallas, TX), were targeted at MI bilaterally (unilateral in intact rats, ipsilateral to the stimulating electrode implantation side). The targeted MI area corresponded to the forelimb territory, and correct location was confirmed by epidural stimulation-induced forelimb movement. Electrode placement and dopamine depletion level were confirmed histologically postmortem.