Abstract
Absence seizures consist of a brief and sudden impairment of consciousness. They are characterized by bilaterally synchronized spike and wave discharges (SWDs), which reflect abnormal oscillations in the thalamocortical loops. Recent studies have suggested that the basal ganglia are involved in generation of the SWDs, but their roles are poorly understood at the molecular and cellular levels. Here we studied the pathophysiological roles of the basal ganglia, using in vivo and in vitro measurements of tottering mice, a well-established model of absence epilepsy. We found that the membrane excitability in subthalamic nucleus (STN) neurons was enhanced in tottering mice, which resulted from reduced hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. Pharmacological blockade and activation of HCN channel activity in vitro bidirectionally altered the membrane excitability of the STN neurons. Furthermore, these pharmacological modulations of HCN channel activity in the STN in vivo bidirectionally altered the mean SWD duration. In addition, STN deep brain stimulation modulated SWDs in a frequency-dependent manner. These results indicate that STN is involved in the rhythm maintenance system of absence seizures.
| Original language | English |
|---|---|
| Pages (from-to) | 393-406 |
| Number of pages | 14 |
| Journal | Journal of Neurophysiology |
| Volume | 107 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2012 |
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Keywords
- Basal ganglia
- Calcium channel mutant mice
- Deep brain stimulation
- Hyperpolarization-activated cyclic nucleotide-gated channel
- Lamotrigine
ASJC Scopus subject areas
- Physiology
- Neuroscience(all)
Cite this
Roles of the subthalamic nucleus and subthalamic HCN channels in absence seizures. / Kase, Daisuke; Inoue, Tsuyoshi; Imoto, Keiji.
In: Journal of Neurophysiology, Vol. 107, No. 1, 01.2012, p. 393-406.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Roles of the subthalamic nucleus and subthalamic HCN channels in absence seizures
AU - Kase, Daisuke
AU - Inoue, Tsuyoshi
AU - Imoto, Keiji
PY - 2012/1
Y1 - 2012/1
N2 - Absence seizures consist of a brief and sudden impairment of consciousness. They are characterized by bilaterally synchronized spike and wave discharges (SWDs), which reflect abnormal oscillations in the thalamocortical loops. Recent studies have suggested that the basal ganglia are involved in generation of the SWDs, but their roles are poorly understood at the molecular and cellular levels. Here we studied the pathophysiological roles of the basal ganglia, using in vivo and in vitro measurements of tottering mice, a well-established model of absence epilepsy. We found that the membrane excitability in subthalamic nucleus (STN) neurons was enhanced in tottering mice, which resulted from reduced hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. Pharmacological blockade and activation of HCN channel activity in vitro bidirectionally altered the membrane excitability of the STN neurons. Furthermore, these pharmacological modulations of HCN channel activity in the STN in vivo bidirectionally altered the mean SWD duration. In addition, STN deep brain stimulation modulated SWDs in a frequency-dependent manner. These results indicate that STN is involved in the rhythm maintenance system of absence seizures.
AB - Absence seizures consist of a brief and sudden impairment of consciousness. They are characterized by bilaterally synchronized spike and wave discharges (SWDs), which reflect abnormal oscillations in the thalamocortical loops. Recent studies have suggested that the basal ganglia are involved in generation of the SWDs, but their roles are poorly understood at the molecular and cellular levels. Here we studied the pathophysiological roles of the basal ganglia, using in vivo and in vitro measurements of tottering mice, a well-established model of absence epilepsy. We found that the membrane excitability in subthalamic nucleus (STN) neurons was enhanced in tottering mice, which resulted from reduced hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. Pharmacological blockade and activation of HCN channel activity in vitro bidirectionally altered the membrane excitability of the STN neurons. Furthermore, these pharmacological modulations of HCN channel activity in the STN in vivo bidirectionally altered the mean SWD duration. In addition, STN deep brain stimulation modulated SWDs in a frequency-dependent manner. These results indicate that STN is involved in the rhythm maintenance system of absence seizures.
KW - Basal ganglia
KW - Calcium channel mutant mice
KW - Deep brain stimulation
KW - Hyperpolarization-activated cyclic nucleotide-gated channel
KW - Lamotrigine
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UR - http://www.scopus.com/inward/citedby.url?scp=84255171131&partnerID=8YFLogxK
U2 - 10.1152/jn.00937.2010
DO - 10.1152/jn.00937.2010
M3 - Article
C2 - 22013231
AN - SCOPUS:84255171131
VL - 107
SP - 393
EP - 406
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
SN - 0022-3077
IS - 1
ER -