Grassi S, Della Torre G, Capocchi G, Zampolini M, Pettorossi V E
Institute of Human Physiology, University of Perugia, Italy.
Brain Res. 1995 Nov 20;699(2):183-91. doi: 10.1016/0006-8993(95)00895-w.
The role of GABA in NMDA-dependent long term depression (LTD) in the medial vestibular nuclei (MVN) was studied on rat brainstem slices. High frequency stimulation (HFS) of the primary vestibular afferents induces a long lasting reduction of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the MVN. The induction but not the maintenance of this depression was abolished by AP5, a specific blocking agent for glutamate NMDA receptors. The involvement of GABA in mediating the depression was checked by applying the GABAA and GABAB receptor antagonists, bicuculline and saclofen, before and after HFS. Under bicuculline and saclofen perfusion, HFS provoked a slight potentiation of the N2 wave, while the N2 depression clearly emerged after drug wash-out. This indicates that GABA is not involved in inducing the long term effect, but it is necessary for its expression. Similarly, the LTD reversed and a slight potentiation appeared when both drugs were administered after its induction. Most of these effects were due to the bicuculline, suggesting that GABAA receptors contribute to LTD more than GABAB do. According to our results, it is unlikely that the long lasting vestibular depression is the result of a homosynaptic LTD. On the contrary, our findings suggest that the depression is due to an enhancement of the GABA inhibitory effect, caused by an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.
在大鼠脑干切片上研究了γ-氨基丁酸（GABA）在内侧前庭核（MVN）中N-甲基-D-天冬氨酸（NMDA）依赖性长时程抑制（LTD）中的作用。对初级前庭传入神经进行高频刺激（HFS）可使在MVN背侧部分记录的场电位的多突触（N2）成分产生持久降低。AP5（一种谷氨酸NMDA受体的特异性阻断剂）可消除这种抑制的诱导，但不能消除其维持。通过在HFS前后应用GABAA和GABAB受体拮抗剂荷包牡丹碱和赛氯芬来检查GABA在介导这种抑制中的作用。在荷包牡丹碱和赛氯芬灌注下，HFS引起N2波的轻微增强，而在药物洗脱后N2抑制明显出现。这表明GABA不参与诱导长期效应，但它是其表达所必需的。同样，当在LTD诱导后同时给予这两种药物时，LTD逆转并出现轻微增强。这些效应大多归因于荷包牡丹碱，表明GABAA受体比GABAB受体对LTD的贡献更大。根据我们的结果，持久的前庭抑制不太可能是同突触LTD的结果。相反，我们的研究结果表明，这种抑制是由于GABA能中间神经元活动的HFS依赖性增加导致GABA抑制作用增强，从而将前庭神经元兴奋性重置在较低水平。
