Mode-dependent effect of high-frequency electrical stimulation of the anterior thalamic nucleus on amygdala-kindled seizures in rats

Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266071, PR China.
Neuroscience (Impact Factor: 3.36). 05/2012; 217:113-22. DOI: 10.1016/j.neuroscience.2012.05.009
Source: PubMed


Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. The present study aimed to investigate the effects of high frequency stimulation (HFS) targeting the ANT on amygdala-kindled seizures in Wistar rats in two different stimulation modes i.e. pre-treatment and post-treatment stimulations, mimicking the scheduled and responsive stimulations in clinical use respectively. When fully-kindled seizures were achieved by daily amygdala kindling (1 s train of 1 ms pulses at 60 Hz), HFS (15 min train of 100 μs pulses at 150 Hz and 450-800 μA) was applied in two modes for 10 days. Bilateral post-treatment with HFS reduced the incidence of generalized seizures and the mean behavioral seizure stage and shortened average afterdischarge duration (ADD) and generalized seizure duration (GSD), while bilateral pre-treatment with HFS resulted in a similar but much weaker inhibition of seizures. On the other hand, we also found the two stimulation modes both increased the afterdischarge threshold (ADT) and the differences of current intensity between ADT and generalized seizure threshold (GST) i.e. Δ(GST-ADT). However, Δ(GST-ADT) increased by at least 20 μA in bilateral post-treatment group, while less in bilateral pre-treatment group. Additionally, unilateral post-treatment with HFS failed to inhibit seizures. Our data show that anti-epileptic effect of bilateral post-treatment with HFS of ANT is much stronger than that of bilateral pre-treatment HFS, indicating bilateral responsive stimulation might be more appropriate for clinical anti-epileptic treatment of ANT HFS.

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    • "Another example of current interest in neuroscience is the electric microstimulation of deep brain structures. This technique is being investigated in preclinical settings to uncover their functional principles and exploit their full clinical possibilities [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]. Stereotaxic neurosurgery is particularly relevant to deep brain stimulation since the precise location of the stimulated cell population will determine the functional outcome [14] [15]. "
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    • "Once anesthetized, rats were positioned in a stereotaxic apparatus (Stoelting, USA). Electrodes were implanted into the right hemisphere aimed at the basolateral amygdale as described previously (AP: −3.0 mm; L: −4.8 mm; V: −8.8 mm) [18], [19]. The above coordinates were determined according to the atlas of Paxinos and Watson (1986). "
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    • "In another rodent epilepsy model, where seizures were induced by electrical stimulation of the basolateral amygdala, low-frequency bilateral ATN stimulation significantly reduced the severity and incidence of seizures (Zhong et al., 2011). Application of bilateral high-frequency stimulation in rats to the ATN after amygdala-induced seizures (e.g., replicating clinical post treatment application) decreased the incidence and duration of subsequent seizures (Zhang et al., 2012a). Another study by the same group showed that unilateral high frequency stimulation of the ATN before amygdala-induced seizures inhibited the induced seizures, and was concluded to suppress susceptibility to seizures (Zhang et al., 2012b). "
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