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HCN Channels Modulate the Activity of the Subthalamic Nucleus In Vivo

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Abstract

The subthalamic nucleus is a key component in the indirect pathway of the basal ganglia, which mediates a variety of motor functions. The subthalamic nucleus neurons have intrinsic pacemaking properties. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are expressed in the central nervous system, including the subthalamic nucleus. However, the in vivo modulation of HCN channels in the subthalamic nucleus remains relatively obscure. To investigate the direct effects of HCN channels in the subthalamic nucleus, multi-barrel extracellular recordings and behavioral tests were performed in the present study. In 42 out of the 89 subthalamic nucleus neurons, micropressure ejection of HCN channel inhibitor, ZD7288 (0.05 mM), decreased the spontaneous firing rate from 11.6 ± 1.8 to 5.7 ± 1.3 Hz (P < 0.001). The average decrease was 56.7 ± 5.3 %. In another 47 out of the 89 subthalamic nucleus neurons, micropressure ejection of ZD7288 increased the spontaneous firing rate from 9.5 ± 1.6 to 16.3 ± 2.4 Hz (P < 0.001), with the average increase of 142.2 ± 29.8 %. Activation of HCN channels by 8-Br-cAMP also produced bidirectional modulation on the firing rate of the subthalamic nucleus neurons. Furthermore, unilateral microinjection of ZD7288 or 8-Br-cAMP produced postural behavior in awake rats. The present electrophysiological and behavioral findings demonstrated that the pharmacological blockade or activation of HCN channels produces bidirectional modulation on the excitability of the subthalamic nucleus.

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Acknowledgments

This work was supported by the grants from the National Natural Science Foundation of China (31070942, 81171208, 81200872) and the Doctoral Fund of the Ministry of Education of China (20123706110001).

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Authors and Affiliations

  1. Department of Neurosurgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China

    Wen-shuai Deng, Peng Sun & Lei Chen

  2. Nursing College, Qingdao University, Qingdao, 266071, China

    Yun-Xia Jiang

  3. Department of Physiology, Qingdao University, Qingdao, 266071, China

    Xiao-Hua Han, Yan Xue & Hua Wang

  4. Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao, 266071, Shandong, China

    Lei Chen

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  1. Wen-shuai Deng
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  2. Yun-Xia Jiang
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  3. Xiao-Hua Han
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  4. Yan Xue
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  5. Hua Wang
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  6. Peng Sun
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  7. Lei Chen
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Correspondence to Peng Sun or Lei Chen.

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Deng, Ws., Jiang, YX., Han, XH. et al. HCN Channels Modulate the Activity of the Subthalamic Nucleus In Vivo. J Mol Neurosci 55, 260–268 (2015). https://doi.org/10.1007/s12031-014-0316-5

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  • DOI: https://doi.org/10.1007/s12031-014-0316-5

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