HCN channels modulate the activity of the subthalamic nucleus in vivo.
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.
Department of Neurosurgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China.
Wen-Shuai
WS
Deng
Nursing College, Qingdao University, Qingdao, 266071, China.
Yun-Xia
YX
Jiang
Department of Physiology, Qingdao University, Qingdao, 266071, China.
Xiao-Hua
XH
Han
Department of Physiology, Qingdao University, Qingdao, 266071, China.
Yan
Y
Xue
Department of Physiology, Qingdao University, Qingdao, 266071, China.
Hua
H
Wang
Department of Neurosurgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China. sunpengqd@163.com.
Peng
P
Sun
Department of Neurosurgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China. chenleiqd@163.com.|Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao, 266071, Shandong, China. chenleiqd@163.com.
Lei
L
Chen
D000200:Action Potentials; D000818:Animals; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000378:metabolism* / Q000502:physiology
D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D011743:Pyrimidines; C082246:ICI D2788