The role of auditory sensory input during functional pre- and postsynaptic maturation of the calyx of Held synapse
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Emilio Erazo-Fischer
Doctoral thesis
Date of Examination:
2006-10-18
Date of issue:
2006-10-23
Advisor:
Taschenberger, Holger Dr.
Referee:
Neher, Erwin Prof. Dr.
Referee:
Stühmer, Walter Prof. Dr.
Referee:
Moser, Tobias Dr.
Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0006-AC2C-3
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Dissertation
Abstract
English
We studied how afferent nerve activity affects the in-vivo maturation of a fast glutamatergic CNS synapse, the calyx of Held. To address this question we exploited the distinct presynaptic Ca2+ channel subtypes governing transmitter release at the cochlear inner hair cell (IHC)-spinal neuron synaptic junction compared to those at higher synapses along the auditory pathways. We characterized functional properties of calyx synapses in wildtype (wt) compared to those developing in CaV1.3 subunit-deficient (CaV1.3-/- deaf) mice. The latter are deaf because of absence of glutamate release from IHC and degeneration of primary afferents and thus completely lack cochlea-driven nerve activity. Ca2+-channel properties, Ca2+ dependence of exocytosis, number of readily releasable quanta and AMPA mEPSCs were unchanged in P14-17 calyx synapses of CaV1.3-/- deaf mice. However, synaptic strength was augmented because presynaptic action potentials were broader leading to increased quantal release, consistent with lower paired-pulse ratios and stronger depression during repetitive synaptic stimulation. Furthermore, asynchronous release following trains was elevated presumably because of higher residual Ca2+ accumulating in the presynaptic terminals. Finally, we measured larger NMDA EPSCs with higher sensitivity to the NR2B subunit-specific antagonist ifenprodil in P14-17 synapses of CaV1.3-/- deaf compared to wt mice. These results suggest that auditory activity is required for the adjustment of synaptic strength as well as for the down regulation of synaptic NMDARs during postnatal development of the calyx of Held. In contrast, properties of the presynaptic release machinery and postsynaptic AMPARs are unaffected by chronic changes in the level of afferent activity at this synapse.
Keywords: EPSC; Calyx of Held; Development; Maturation; MNTB; Synaptic
