Home Research Project Details A5 - Cellular decomposition of auditory information in the mammalian cochlea
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A5 - Cellular decomposition of auditory information in the mammalian cochlea

Alexander Meyer, Tobias Moser, and Fred Wolf

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):

Chapochnikov, NM, Takago, H, Huang, C, Pangrsic, T, Khimich, D, Neef, J, Auge, E, Goettfert, F, Hell, SW, Wichmann, C, Wolf, F, and Moser, T (2014).
Uniquantal Release through a Dynamic Fusion Pore Is a Candidate Mechanism of Hair Cell Exocytosis
Neuron 83(6):1389-1403.

Schulz, AM, Jing, Z, Sanchez Caro, JM, Wetzel, F, Dresbach, T, Strenzke, N, Wichmann, C, and Moser, T (2014).
Bassoon‐disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse
The EMBO Journal 33(5):512-27.

Wong, AB, Rutherford, MA, Gabrielaitis, M, Pangrsic, T, Göttfert, F, Frank, T, Michanski, S, Hell, S, Wolf, F, Wichmann, C, and Moser, T (2014).
Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis
The EMBO Journal 33(3):247-64.

Wong, AB, Jing, Z, Rutherford, MA, Frank, T, Strenzke, N, and Moser, T (2013).
Concurrent maturation of inner hair cell synaptic Ca2+ influx and auditory nerve spontaneous activity around hearing onset in mice
The Journal of Neuroscience 33(26):10661-10666.

Rutherford, MA, Chapochnikov, NM, and Moser, T (2012).
Spike encoding of neurotransmitter release timing by spiral ganglion neurons of the cochlea
J Neurosci 32(14):4773-89.

Gregory, FD, Bryan, KE, Pangršič, T, Calin-Jageman, IE, Moser, T, and Lee, A (2011).
Harmonin inhibits presynaptic Ca(v)1.3 Ca(2+) channels in mouse inner hair cells
Nat Neurosci 14:1109-11.

Reisinger, E, Bresee, C, Neef, J, Nair, R, Reuter, K, Bulankina, A, Nouvian, R, Koch, M, Bückers, J, Kastrup, L, Roux, I, Petit, C, Hell, SW, Brose, N, Rhee, JS, Kügler, S, Brigande, J, and Moser, T (2011).
Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis
J Neuroscience 30(31):4886-95.