title: Morphological and functional continuum underlying heterogeneity in the spiking fidelity at the calyx of Held synapse in vitro.
abstract: Reliable neuronal spiking is critical for a myriad of computations performed by neural circuits. This is particularly evident for sound localization cues in the auditory brainstem circuits that detect timing and intensity differences of sounds arriving at two ears. The calyx of Held-principal neuron synapse in the medial nucleus of the trapezoid body (MNTB) in this circuit is traditionally viewed as a reliable relay, which converts contralateral excitatory inputs to inhibitory outputs to ipsilateral superior olive neurons that code interaural timing and intensity differences. However, recent studies demonstrated large variability in the incidence of postsynaptic spike failures at this synapse, challenging the view that this synapse is a fail-safe relay. Using combined imaging and paired recordings in mature (P16-P19) mouse brainstem slices, we show that spike failure rates of MNTB neurons are strongly correlated with differences in gross morphology of the calyx terminal and quantal properties under standard in vitro- and in vivo-like conditions. MNTB neurons innervated by calyces with simple morphologies (mainly digits) express strong short-term synaptic depression and a high incidence of spike failures after high-frequency stimulation. Conversely, MNTB neurons innervated by structurally complex calyces (digits and numerous bouton-like swellings) exhibit initial facilitation followed by slow depression and very few spike failures. Our results indicate that the calyx of Held-MNTB synapse is likely organized as a structural and functional continuum, in that correlated heterogeneities in calyx morphology and short-term plasticity serve as a filter for regulating the inhibition delivered to superior olive neurons during sound localization.
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8.
authors.forename: Giovanbattista
authors.initials: G
authors.lastname: Grande
authors.forename: Lu-Yang
authors.initials: LY
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001306:Auditory Pathways / Q000033:anatomy & histology / Q000502:physiology; D001933:Brain Stem / Q000033:anatomy & histology* / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000502:physiology*; D013017:Sound Localization / Q000502:physiology; D013569:Synapses / Q000502:physiology*