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Symposia
Author(s) -
Chan, YS,
Han, L,
Chan, WC,
Lam, YL,
Ma, CW,
Shum, DKY
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12775
Subject(s) - citation , library science , neurochemistry , computer science , world wide web , psychology , neuroscience , neurology
Symposia S09: Synaptic and Network Plasticity in Development and LearningPerineuronal heparan sulfates (HS) have been implicated in
controlling the open-state of AMPA-type glutamate receptors
(AMPARs) which govern excitatory synaptic transmission. Our
finding of neuronal heparanase-immunoreactivity in the rat vestibular
nucleus (VN) led us to test if the secreted form acts on
perineuronal HS as means to regulate synaptic function in the
vestibular circuit. We however found enhanced secretion of
enzymatically inactive proheparanase into the medium of VN
explants treated with phorbol ester to induce exocytosis. Treatment
of VN cultures with recombinant proheparanase triggered (i)
neuronal internalization of HS-associated AMPAR and (ii)
decrease in glutamate-induced calcium influx into neurons. VNcontaining brainstem slices subjected to whole-cell patch-clamp
studies revealed decrease in amplitudes of excitatory postsynaptic
currents following phorbol ester treatment. These findings suggest
that activity-dependent secretion of proheparanase induces internalization
of HS-associated AMPAR at glutamatergic synapses of
VN interneurons. We then asked if proheparanase plays a part in
the maturation of the central vestibular circuitry. Immunohistochemical
analysis of the VN revealed colocalization of HSsyndecan
and heparanase on GABAergic interneurons, contrasting
that of HS-perlecan in perineuronal nets. Intensification of both
perineuronal HS and cellular heparanase immunoreactivities with
postnatal development was time-matched with consolidation of
perineuronal nets of GABAergic neurons. In vivo, neonatal
perturbation of either glutamatergic input to the neurons with
CNQX or GABAergic output of the neuron with bicuculline
delayed the postnatal onset of negative geotaxis (readout of
vestibular reflex). Taken together, our results suggest that activitydependent
production of proheparanase triggers internalization of
AMPAR at GABAergic interneurons in the VN within a period
critical for the postnatal maturation of vestibular function.
[Supported by HKRGC-GRF Grant 774608]link_to_OA_fulltex