Moore Lucille A, Trussell Laurence O
Neuroscience Graduate Program and
Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239.
J Neurosci. 2017 Sep 27;37(39):9453-9464. doi: 10.1523/JNEUROSCI.1125-17.2017. Epub 2017 Aug 28.
The central nucleus of the inferior colliculus (ICC) of the auditory midbrain, which integrates most ascending auditory information from lower brainstem regions, receives prominent long-range inhibitory input from the ventral nucleus of the lateral lemniscus (VNLL), a region thought to be important for temporal pattern discrimination. Histological evidence suggests that neurons in the VNLL release both glycine and GABA in the ICC, but functional evidence for their corelease is lacking. We took advantage of the mouse line (both male and female) to target expression of ChR2 to glycinergic afferents in the ICC and made whole-cell recordings while exciting glycinergic fibers with light. Using this approach, it was clear that a significant fraction of glycinergic boutons corelease GABA in the ICC. Viral injections were used to target ChR2 expression specifically to glycinergic fibers ascending from the VNLL, allowing for activation of fibers from a single source of ascending input in a way that has not been previously possible in the ICC. We then investigated aspects of the glycinergic versus GABAergic current components to probe functional consequences of corelease. Surprisingly, the time course and short-term plasticity of synaptic signaling were nearly identical for the two transmitters. We therefore conclude that the two neurotransmitters may be functionally interchangeable and that multiple receptor subtypes subserving inhibition may offer diverse mechanisms for maintaining inhibitory homeostasis. Corelease of neurotransmitters is a common feature of the brain. GABA and glycine corelease is particularly common in the spinal cord and brainstem, but its presence in the midbrain is unknown. We show corelease of GABA and glycine for the first time in the central nucleus of the inferior colliculus of the auditory midbrain. Glycine and GABA are both inhibitory neurotransmitters involved in fast synaptic transmission, so we explored differences between the currents to establish a physiological foundation for functional differences In contrast to the auditory brainstem, coreleased GABAergic and glycinergic currents in the midbrain are strikingly similar. This apparent redundancy may ensure homeostasis if one neurotransmitter system is compromised.
听觉中脑下丘中央核（ICC）整合了来自脑干下部区域的大部分上行听觉信息，它接收来自外侧丘系腹侧核（VNLL）的显著的长程抑制性输入，VNLL被认为在时间模式辨别中很重要。组织学证据表明，VNLL中的神经元在ICC中释放甘氨酸和GABA，但缺乏它们共同释放的功能证据。我们利用小鼠品系（雄性和雌性）将ChR2的表达靶向ICC中的甘氨酸能传入纤维，并在用光刺激甘氨酸能纤维时进行全细胞记录。使用这种方法，很明显ICC中有相当一部分甘氨酸能终扣共同释放GABA。病毒注射用于将ChR2的表达特异性靶向从VNLL上行的甘氨酸能纤维，从而以一种以前在ICC中无法实现的方式激活来自单一上行输入源的纤维。然后，我们研究了甘氨酸能与GABA能电流成分的各个方面，以探究共同释放的功能后果。令人惊讶的是，两种递质的突触信号的时间进程和短期可塑性几乎相同。因此，我们得出结论，这两种神经递质在功能上可能是可互换的，并且多种参与抑制的受体亚型可能提供维持抑制性内稳态的多种机制。神经递质的共同释放是大脑的一个共同特征。GABA和甘氨酸的共同释放在脊髓和脑干中尤为常见，但其在中脑中的存在情况尚不清楚。我们首次在听觉中脑下丘中央核中展示了GABA和甘氨酸的共同释放。甘氨酸和GABA都是参与快速突触传递的抑制性神经递质，因此我们探究了电流之间的差异，以建立功能差异的生理基础。与听觉脑干不同，中脑中共同释放的GABA能和甘氨酸能电流惊人地相似。如果一个神经递质系统受损，这种明显的冗余可能确保内稳态。
