Center for Neural Science, New York University New York, NY, USA.
Center for Neural Science, New York University New York, NY, USA ; Department of Biology, New York University New York, NY, USA.
Front Neural Circuits. 2014 Jun 19;8:67. doi: 10.3389/fncir.2014.00067. eCollection 2014.
Principal neurons of the lateral superior olivary nucleus (LSO) respond selectively to interaural level differences (ILD). To perform this computation, LSO neurons integrate excitatory synaptic drive from the ipsilateral ear with inhibitory synaptic drive from the contralateral ear via the medial nucleus of the trapezoid body (MNTB). Previous research demonstrated that inhibitory terminals from the MNTB to the LSO are eliminated during development. Furthermore, MNTB synapses display an activity- and age-dependent long-term depression (iLTD) that may contribute to inhibitory synapse elimination. However, inhibitory synapses that are stabilized become stronger. Here, we asked whether MNTB synapses displayed activity-dependent strengthening. Whole-cell recordings were obtained from LSO neurons in a gerbil brain slice before and after hearing onset. The inhibitory MNTB afferents were stimulated at a low rate, similar to spontaneous discharge rates observed in vivo. The MNTB-evoked inhibitory responses were strengthened by 40-300% when synaptic activity was coupled with postsynaptic membrane depolarization, exogenous glutamate application, or activation of ipsilateral excitatory synaptic inputs. This inhibitory long-term potentiation (iLTP) was associated with increased spontaneous inhibitory postsynaptic current (IPSC) amplitude and frequency. One hour after iLTP induction, IPSCs could not be de-potentiated by the MNTB stimulation pattern that induces iLTD in control slices. iLTP could only be induced after hearing onset (>P12), and was blocked in the presence of a GABAB receptor antagonist. Together, these results suggest a developmental period during which the induction of iLTP depends on the conjoint activation of GABAB receptors and postsynaptic depolarization. We propose that iLTP may support stabilization of un-pruned MNTB connections and contribute to the emergence of ILD processing in the mature LSO.
外侧上橄榄核（LSO）的主要神经元对两耳间水平差异（ILD）有选择性反应。为了进行这种计算，LSO 神经元通过梯形束内侧核（MNTB）整合来自同侧耳的兴奋性突触驱动和来自对侧耳的抑制性突触驱动。先前的研究表明，MNTB 到 LSO 的抑制性末梢在发育过程中被消除。此外，MNTB 突触表现出与活动和年龄相关的长时程抑制（iLTD），这可能有助于抑制性突触消除。然而，稳定的抑制性突触会变得更强。在这里，我们询问 MNTB 突触是否表现出与活动相关的增强。在一只沙鼠脑切片中，在听觉出现前后，从 LSO 神经元获得全细胞膜片钳记录。抑制性 MNTB 传入在低速率下被刺激，类似于体内观察到的自发放电率。当突触活动与突触后膜去极化、外源性谷氨酸应用或激活同侧兴奋性突触输入偶联时，MNTB 诱发的抑制反应增强了 40-300%。这种抑制性长时程增强（iLTP）与自发抑制性突触后电流（IPSC）幅度和频率的增加有关。在 iLTP 诱导后 1 小时，IPSCs 不能被诱导 iLTD 的对照切片中的 MNTB 刺激模式去极化。iLTP 只能在听觉出现后（>P12）诱导，并且在存在 GABA B 受体拮抗剂的情况下被阻断。综上所述，这些结果表明，在发育过程中，iLTP 的诱导取决于 GABA B 受体和突触后去极化的共同激活。我们提出，iLTP 可能支持未修剪的 MNTB 连接的稳定，并有助于成熟 LSO 中 ILD 处理的出现。
