title: The extracellular matrix molecule brevican is an integral component of the machinery mediating fast synaptic transmission at the calyx of Held.
abstract: CONCLUSIONS
  The proteoglycan brevican is a major component of the extracellular matrix of perineuronal nets and is highly enriched in the perisynaptic space suggesting a role for synaptic transmission. We have introduced the calyx of Held in the auditory brainstem as a model system to study the impact of brevican on dynamics and reliability of synaptic transmission. In vivo extracellular single-unit recordings at the calyx of Held in brevican-deficient mice yielded a significant increase in the action potential (AP) transmission delay and a prolongation of pre- and postsynaptic APs. The changes in dynamics of signal transmission were accompanied by the reduction of presynaptic vGlut1 and ultrastructural changes in the perisynaptic space. These data show that brevican is an important mediator of fast synaptic transmission at the calyx of Held.
  The extracellular matrix is an integral part of the neural tissue. Its most conspicuous manifestation in the brain are the perineuronal nets (PNs) which surround somata and proximal dendrites of distinct neuron types. The chondroitin sulfate proteoglycan brevican is a major component of PNs. In contrast to other PN-comprising proteoglycans (e.g. aggrecan and neurocan), brevican is mainly expressed in the perisynaptic space closely associated with both the pre- and postsynaptic membrane. This specific localization prompted the hypothesis that brevican might play a role in synaptic transmission. In the present study we specifically investigated the role of brevican in synaptic transmission at a central synapse, the calyx of Held in the medial nucleus of the trapezoid body, by the use of in vivo electrophysiology, immunohistochemistry, biochemistry and electron microscopy. In vivo extracellular single-unit recordings were acquired in brevican-deficient mice and the dynamics and reliability of synaptic transmission were compared to wild-type littermates. In knockout mice, the speed of pre-to-postsynaptic action potential (AP) transmission was reduced and the duration of the respective pre- and postsynaptic APs increased. The reliability of signal transmission, however, was not affected by the lack of brevican. The changes in dynamics of signal transmission were accompanied by the reduction of (i) presynaptic vGlut1 and (ii) the size of subsynaptic cavities. The present results suggest an essential role of brevican for the functionality of high-speed synaptic transmission at the calyx of Held.
authors.affiliation: Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Blosa
authors.affiliation: Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, 04103, Leipzig, Germany.|Institute of Biology, Faculty of Biology, Pharmacy and Psychology, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Mandy
authors.initials: M
authors.lastname: Sonntag
authors.affiliation: Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Jäger
authors.affiliation: Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Solveig
authors.initials: S
authors.lastname: Weigel
authors.affiliation: Institute of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Seeger
authors.affiliation: Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany.
authors.forename: Renato
authors.initials: R
authors.lastname: Frischknecht
authors.affiliation: Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany.
authors.forename: Constanze I
authors.initials: CI
authors.lastname: Seidenbecher
authors.affiliation: Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Russell T
authors.initials: RT
authors.lastname: Matthews
authors.affiliation: Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.affiliation: Institute of Biology, Faculty of Biology, Pharmacy and Psychology, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Rübsamen
authors.affiliation: Paul Flechsig Institute for Brain Research, Faculty of Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Morawski
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials; D000818:Animals; D058581:Brevican / Q000235:genetics / Q000502:physiology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005109:Extracellular Matrix; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D065833:Trapezoid Body / Q000378:metabolism / Q000502:physiology*
chemical_list: C553057:Bcan protein, mouse; D058581:Brevican; D027342:Excitatory Amino Acid Transporter 2; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; C493396:Slc1a2 protein, mouse; C495678:Slc2a1 protein, mouse; C495682:Slc2a2 protein, mouse