Development of a robust central auditory synapse in congenital deafness.
Within the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, there is a large central synapse known as the calyx of Held, which mediates high-fidelity glutamatergic transmission. We investigated the effects of congenital deafness on the development of pre- and postsynaptic parameters of synaptic strength at the calyx of Held. Whole cell recordings of evoked excitatory postsynaptic currents (EPSCs) and immunohistochemistry of GluR1-4 subunits were performed using brain stem slices from congenitally deaf or hearing mice at postnatal days P5 and P12. In both hearing and deaf mice there was a similar developmental decrease in the NMDA component of the evoked EPSC. There was a concurrent increase in release probability and number of release sites, contributing to a fivefold increase in evoked AMPA-mediated EPSC amplitude. The increase in release probability is opposite to that found in previous studies at the calyx of Held in the rat. There was also a seven- to eightfold increase in the size of the readily releasable pool of vesicles and a decrease in tetanic depression. The postsynaptic glutamate receptor subunits were similarly developmentally regulated and unaffected by deafness. GluR1 and 4 dominated at both ages. There was a decrease in expression of GluR1-3 from P5 to P12 and a shift from GluR2 to GluR3, indicating that AMPA receptor complexes at P12 are predominantly calcium-permeable. These results demonstrate that early development at this robust synapse proceeds normally with congenital deafness, suggesting that auditory nerve activity does not affect the development of synaptic strength at the calyx of Held.
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2600, Australia. Monique.Youssoufian@anu.edu.au
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M
Youssoufian
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Oleskevich
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Walmsley
D000818:Animals; D000831:Animals, Newborn; D001306:Auditory Pathways / Q000503:physiopathology; D001933:Brain Stem / Q000503:physiopathology*; D003056:Cochlear Nerve / Q000502:physiology*; D003638:Deafness / Q000151:congenital* / Q000503:physiopathology*; D005072:Evoked Potentials, Auditory; D019706:Excitatory Postsynaptic Potentials; D051379:Mice; D008808:Mice, Inbred CBA; D008818:Mice, Neurologic Mutants; D009473:Neuronal Plasticity; D009475:Neurons, Afferent; D013569:Synapses; D009435:Synaptic Transmission