Lessle Sascha, Ebbers Lena, Dörflinger Yvette, Hoppe Simone, Kaiser Michaela, Nothwang Hans Gerd, Körber Christoph
Department of Functional Neuroanatomy, Institute of Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
Division of Neurogenetics, Center of Excellence Hearing4All, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
Front Cell Neurosci. 2024 Nov 18;18:1404206. doi: 10.3389/fncel.2024.1404206. eCollection 2024.
Activity has long been considered essential for circuit formation and maintenance. This view has recently been challenged by proper synaptogenesis and only mildly affected synapse maintenance in the absence of synaptic activity in forebrain neurons. Here, we investigated whether synaptic activity is necessary for the development and maintenance of the calyx of Held synapse. This giant synapse located in the auditory brainstem is highly specialized to maintain high frequency, high-fidelity synaptic transmission for prolonged times and thus shows particularly high synaptic activity. We expressed the protease tetanus toxin light chain (TeNT) exclusively in bushy cells of the ventral cochlear nucleus (VCN) of juvenile mice. Since globular bushy cells give rise to the calyx of Held, expression of TeNT in these cells specifically abolished synaptic transmission at the calyx without impairing general functionality of the central auditory system. Calyces lacked synaptic activity after two weeks of TeNT expression. However, this did not lead to major changes in presynaptic morphology, the number of active zones (AZs) or the composition of postsynaptic AMPA-type glutamate receptors (GluAs). Moreover, the fenestration of the calyx of Held, a hallmark of structural maturation, occurred normally. We thus show that the maintenance of a specialized high frequency synapse in the auditory brainstem occurs in a hardwired, probably genetically encoded, manner with little dependence on synaptic activity.
长期以来，活动一直被认为是神经回路形成和维持所必需的。最近，这一观点受到了挑战，因为在前脑神经元缺乏突触活动的情况下，突触能够正常形成，而突触维持仅受到轻微影响。在此，我们研究了突触活动对于Held壶腹突触的发育和维持是否必要。这个位于听觉脑干的巨大突触高度特化，能够长时间维持高频、高保真的突触传递，因此表现出特别高的突触活动。我们在幼年小鼠的腹侧耳蜗核（VCN）的浓密细胞中特异性表达了蛋白酶破伤风毒素轻链（TeNT）。由于球状浓密细胞产生Held壶腹，在这些细胞中表达TeNT可特异性消除壶腹处的突触传递，而不损害中枢听觉系统的一般功能。在表达TeNT两周后，壶腹缺乏突触活动。然而，这并未导致突触前形态、活性区（AZs）数量或突触后AMPA型谷氨酸受体（GluAs）组成的重大变化。此外，Held壶腹的窗孔形成，即结构成熟的标志，正常发生。因此，我们表明，听觉脑干中特化高频突触的维持以一种硬连线的、可能由基因编码的方式发生，对突触活动的依赖性很小。
