Xie Yijing, Heida Tjitske, Stegenga Jan, Zhao Yan, Moser Andreas, Tronnier Volker, Feuerstein Thomas J, Hofmann Ulrich G
Neuroelectronic Systems, Department of Neurosurgery, University Medical Center Freiburg, 79108, Freiburg, Germany; Graduate School for Computing in Medicine and Life Sciences, University of Lübeck, Lübeck, Germany.
Eur J Neurosci. 2014 Dec;40(11):3653-62. doi: 10.1111/ejn.12736. Epub 2014 Sep 23.
The nucleus accumbens is selected as a surgical target in deep brain stimulation for treating refractory obsessive-compulsive disorder (OCD). One of the therapeutic benefits of this procedure is that the abnormal hyper-functioning prefrontal cortex of patients with OCD is restored during stimulation. One hypothesis regarding the mechanism of deep brain stimulation is that the neuronal electrophysiological properties are directly altered by electrical stimulation; another hypothesis assumes that the stimulation induces selective neuron transmitter release, such as γ-aminobutyric acid (GABA). In this study, we used multi-electrode arrays with electrode size of 40 × 40 μm to record electrophysiological signals from the large nucleus accumbens neurons in acute rat brain slices while applying electrical stimulation simultaneously. We revealed that high-frequency stimulation (HFS, 140 Hz) suppressed the spontaneous neuronal firing rate significantly, whereas low-frequency stimulation (LFS, 10 Hz) did not. Both HFS and LFS have no effect on neuronal firing pattern or on neuronal oscillation synchrony. GABAB receptor antagonism reversed the HFS-provoked neuronal inhibition, whereas GABAA receptor blockade failed to affect it. The recorded neurons were pharmacologically identified to be cholinergic interneurons. We propose that HFS has a direct suppressive effect on the identified accumbal acetylcholine (ACh) interneurons by enhancing GABA release in the stimulated region. Potentially, suppressed ACh interneurons decrease the disinhibiting function of medium-sized spiny neurons in the striato-thalamo-cortical circuit. This finding might give an indication of the mechanism of the therapeutic effect of HFS in nucleus accumbens on restoring the abnormal hyperactive prefrontal cortex status in OCD.
伏隔核被选为深部脑刺激治疗难治性强迫症（OCD）的手术靶点。该手术的治疗益处之一是，在刺激过程中，强迫症患者功能亢进的异常前额叶皮层得以恢复。关于深部脑刺激机制的一种假设是，电刺激直接改变神经元的电生理特性；另一种假设则认为，刺激会诱导选择性神经递质释放，如γ-氨基丁酸（GABA）。在本研究中，我们使用电极尺寸为40×40μm的多电极阵列，在急性大鼠脑切片中记录伏隔核大神经元的电生理信号，同时施加电刺激。我们发现，高频刺激（HFS，140Hz）显著抑制了神经元的自发放电率，而低频刺激（LFS，10Hz）则没有。HFS和LFS对神经元放电模式或神经元振荡同步性均无影响。GABAB受体拮抗剂可逆转HFS引起的神经元抑制，而GABAA受体阻断剂则未能产生影响。经药理学鉴定，记录的神经元为胆碱能中间神经元。我们提出，HFS通过增强刺激区域的GABA释放对已鉴定的伏隔核乙酰胆碱（ACh）中间神经元具有直接抑制作用。潜在地，被抑制的ACh中间神经元会降低纹状体-丘脑-皮质回路中中等棘状神经元的去抑制功能。这一发现可能为伏隔核中HFS恢复OCD患者异常活跃的前额叶皮层状态的治疗效果机制提供线索。
