title: Fenestration of the calyx of Held occurs sequentially along the tonotopic axis, is influenced by afferent activity, and facilitates glutamate clearance.
abstract: The calyx of Held is a type of giant glutamatergic presynaptic terminal in the mammalian auditory brainstem that transmits afferent information from the cochlear nucleus to the medial nucleus of the trapezoid body (MNTB). It participates in sound localization, a process that requires very high temporal precision. Consistent with its functional role, the calyx shows a number of specializations for temporal fidelity, one of them being the giant terminal itself with its many release sites. During the first 3 weeks of postnatal development, the calyx transforms from a spoon-shaped, closed morphology to a highly fenestrated open structure. Calyces in Mongolian gerbils (Meriones unguiculatus) were labeled via injection of fluorescent tracers and their morphology was reconstructed at various timepoints during early postnatal development. We show that the fenestration process does not occur simultaneously in all calyces. Calyces transmitting high-frequency sound information fenestrate significantly earlier than those transmitting low-frequency information, such that a temporary developmental gradient along the tonotopic axis is established around the time of hearing onset. Animals that were deprived of afferent activity before hearing onset, either via cochlear removal or administration of ototoxic drugs, do not show this developmental gradient. Glial processes containing glutamate transporters occupy the newly created windows in the calyx and thus could augment the fast clearance of neurotransmitter. The physiological consequences of this faster clearance include a faster decay time course of synaptic currents as well as a lower amount of residual current accumulating during the processing of repeated activity such as stimulus trains.
authors.affiliation: Division of Neurobiology, Ludwig-Maximilians-University Munich, Martinsried, Germany.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Ford
authors.forename: Benedikt
authors.initials: B
authors.lastname: Grothe
authors.forename: Achim
authors.initials: A
authors.lastname: Klug
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001306:Auditory Pathways / Q000502:physiology; D001307:Auditory Perception / Q000502:physiology; D001933:Brain Stem / Q000033:anatomy & histology / Q000254:growth & development* / Q000502:physiology*; D003051:Cochlea / Q000601:surgery; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D005849:Gerbillinae; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D007612:Kanamycin / Q000633:toxicity; D008297:Male; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D017729:Presynaptic Terminals / Q000502:physiology*
chemical_list: D009498:Neurotoxins; D018698:Glutamic Acid; D007612:Kanamycin