A5 - Cellular decomposition of auditory information in the mammalian cochlea
The large range of physiologically relevant sound pressures (approximately 6 orders of magnitude) is collectively encoded by neurons that each signal only a fraction of this sound pressure range to the CNS. It is thought that each inner hair cell drives 10 to 20 neurons with differing relationships between sound pressure and their spike rate [Libermann 1980]. However, how this is achieved in the isopotential presynaptic hair cell and/or the postsynaptic afferent neurite remains a key question in auditory neuroscience. Our recent experimental work has identified presynaptic Ca2+ signalling as a candidate mechanism for synaptic heterogeneity within individual hair cells [Frank et al. 2009, Meyer et al. 2009]. In brief, we could demonstrate up to 10 fold differences among the amplitudes of presynaptic Ca2+ microdomains within an individual hair cell. We indicated that their heterogeneity arises from differences in the number of presynaptic Ca2+ channels and, on top of that, disparate voltage dependencies of channel gating between individual synapses. In addition, differences in the mode of release among the active zones have been postulated as a candidate mechanism (Grant et al., 2010).
Here we setout for experiments and modelling on the mechanisms underlying the cellular decomposition of sound intensity by the various ribbon synapses of an individual hair cell. First, we plan to consolidate our hypothesis of different Ca2+ channel complements and their relationship to the Ca2+ microdomain amplitudes. This will involve further characterization of Ca2+ microdomains by analysis of fluctuations in Ca2+ indicator fluorescence and modelling of the Ca2+ signal. In a second step we will study the impact of Ca2+ microdomain heterogeneity on presynaptic transmitter release by combining fast confocal imaging of Ca2+ signals and synaptic vesicle exocytosis using pHluorin fluorescence. Imaging of exocytosis will test our model predictions and reveal additional insights into synaptic heterogeneity. In a third step we will theoretically examine the potential impact of postsynaptic candidate mechanisms for differential sound intensity coding – such as differences in membrane conductance and sodium channel density. We will integrate the individual models (presynaptic, postsynaptic) into a comprehensive model of sound encoding that shall be evaluated by single auditory nerve fibre recordings done in collaboration with the Strenzke lab.
Belongs to Group(s):
Theoretical Neurophysics,
Physiology of the hair cell ribbon synapse
Is part of Section A
Members working within this Project:
Wolf, Fred
Meyer, Alexander
Moser, Tobias
Selected Publication(s):