The calyx of Held is probably the largest synaptic terminal in the brain, forming a unique one-to-one connection in the auditory ventral brainstem. During early development, calyces have many collaterals, whose function is unknown. Using electrophysiological recordings and fast-calcium imaging in brain slices, we demonstrate that these collaterals are involved in synaptic transmission. We show evidence that the collaterals are pruned and that the pruning already begins 1 week before the onset of hearing. Using two-photon microscopy to image the calyx of Held in neonate rats, we report evidence that both axons and nascent calyces are structurally dynamic, showing the formation, elimination, extension, or retraction of up to 65% of their collaterals within 1 hour. The observed dynamic behavior of axons may add flexibility in the choice of postsynaptic partners and thereby contribute to ensuring that each principal cell eventually is contacted by a single calyx of Held.auditory system ͉ medial nucleus of the trapezoid body ͉ two-photon imaging ͉ structural plasticity ͉ axon collateral S tudying the formation of individual, identified synapses in the CNS presents a formidable challenge because of their small size, their incredibly high density, and their protracted formation period (1). Imaging studies in living animals have provided insights into the structural changes that presynaptic axons undergo during development, which complements our understanding of how specific brain connections form (2). An emerging view from these studies is that axonal dynamics are age-and cell type-dependent (3) and strongly correlated with the formation of synaptic contacts, which may ultimately guide the growth of the axonal arbor (2, 4-6).Here, we study the development of a CNS synapse that can be identified relatively easily because it is probably the largest synaptic contact in the mammalian brain (7). The calyx of Held connects the globular bushy cells of the anteroventral cochlear nucleus and the principal cells of the medial nucleus of the trapezoid body (MNTB) in the brainstem. Studies in rodents have shown that shortly before birth, the principal cells of the MNTB are innervated by small glutamatergic boutons (8). Morphological and functional identification of nascent calyces is possible between postnatal days 3 and 5 (8-10), which suggests that the characteristic one-to-one innervation observed in mature animals is achieved very rapidly (10). However, previous studies have not been able to study the dynamic aspects of the calyx of Held development.As a first step toward elucidating the cellular mechanisms that ensure that each MNTB principal cell is always innervated by only a single calyx of Held, we sought an imaging approach. Because it has not been possible to study this unique synapse in culture, we carried out studies in vivo. We developed a surgical procedure to label brainstem axons in anesthetized rat pups and imaged them with a two-photon microscope. Using this approach, we provide evidence of structural dynamics r...

The calyx of Held synapse is a giant axosomatic synapse that acts as a fast relay in the sound localization circuit of the brainstem. In rodents it forms within a relatively brief period starting around the second postnatal day (P2). The relative timing of the formation of its pre- and the postsynaptic compartment are not yet known. By means of fluorescent immunohistochemistry in neonatal rats we therefore compared the developmental expression patterns of the vesicular glutamate transporter (VGLUT)-1 and the postsynaptic density scaffolding proteins Homer-1 and PSD-95 in the medial nucleus of the trapezoid body (MNTB). Before its formation, colocalized punctate staining of VGLUT-1 and Homer-1 or PSD-95 was observed on principal neurons, in agreement with earlier work showing that they are already innervated by fibers from the cochlear nucleus before the calyx forms. The expression of VGLUT-1 clusters within the nascent calyx of Held synapse preceded the expression of Homer-1 and PSD-95 clusters, as indicated by the presence of principal neurons with only a large contiguous cluster (LCC) of VGLUT-1 at P2-3, whereas no neurons with only an LCC for Homer-1 or PSD-95 were seen. At P3 the first principal neurons with both a pre- and a postsynaptic LCC were observed, and at P12 all principal neurons had both a pre- and a postsynaptic LCC. The relatively late appearance of Homer-1 and PSD-95 within the developing calyx of Held synapse suggests that they play a role in its stabilization and the recruitment of additional receptors to its postsynaptic density.

BackgroundPercutaneous transforaminal endoscopic discectomy (PTED) has emerged as a less invasive technique to treat symptomatic lumbar disk herniation (LDH). PTED is performed under local anesthesia with the advantage of immediate intraoperative feedback of the patient. In this paper, the technique is described as conducted in our hospital.MethodsPTED is performed under local anesthesia in prone position on thoracopelvic supports. The procedure is explained stepwise: e.g. marking, incision, introduction of the 18-gauge needle and guidewire to the superior articular process, introduction of the TomShidi needle and foraminotomy up to 9 mm, with subsequently removal of disk material through the endoscope. Scar size is around 8 mm.ConclusionPTED seems a promising alternative to conventional discectomy in patients with LDH and can be performed safely.Electronic supplementary materialThe online version of this article (10.1007/s00701-018-3723-5) contains supplementary material, which is available to authorized users.

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BackgroundCervical radiculopathy is characterized by dysfunction of the nerve root usually caused by a cervical disk herniation. The most important symptom is pain, radiating from the neck to the arm. When conservative treatment fails, surgical treatment is indicated to relieve symptoms. During the last decades, multiple fusion techniques have been developed, although without clinical evidence for added value of fusion over non-fusion.MethodsThe surgical procedure of anterior cervical discectomy without fusion is performed step by step, leading to removal of the entire intervertebral disk.ConclusionAnterior cervical discectomy without fusion is a safe and effective treatment for cervical disk herniation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00701-017-3189-x) contains supplementary material, which is available to authorized users.