Max Planck Institute for Dynamics and Self-Organization -- Department for Nonlinear Dynamics and Network Dynamics Group
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Towards a theory of efficient stimulus encoding at auditory synapses


Figure 1: Competing hypotheses for the molecular organization of vesicle release at inner hair cell ribbon synapses. (A) A schematic of an inner hair cell ribbon synapse. (B) Scenario of Ca2+-synchronized multiquantal vesicle release. (C) Scenario of the homotypic-fusion based multiquantal vesicle release. Modified from [1].

All information from the auditory world is conveyed to the brain by axonal fibers of the auditory nerve. In mammals, each of these fibers is exclusively driven by single presynaptic active zones of inner hair cell ribbon synapses (Fig. A). The molecular mechanisms of functioning of these synapses are still poorly understood. Combining detailed biophysical models with experimental approaches, including electrophysiology, electron and super-resolution light microscopy, we showed that exocytosis of single synaptic vesicles at these synapses is sufficient to trigger action potentials in auditory nerve fibers [1]. This study also ruled out different hypothetical vesicle release types (Fig. B,C) that had been proposed over the past decade. In further studies, we found that the coupling of the presynaptic Ca2+ channels and sensors of exocytosis is very tight due to the molecular organization of the active zone [23] and high concentrations of Ca2+ buffering proteins [3]. Based on this advanced characterization, we developed analytically tractable but molecularly accurate models of auditory sound encoding and used them to predict optimized molecular designs of the inner hair cell ribbon synapses from efficient coding principles.

[1]    N.M. Chapochnikov, H. Takago, C.-H. Huang, T. Pangrsic, D. Khimich, J. Neef, E. Auge, F. Goettfert, S.W. Hell, C. Wichmann, F. Wolf, T. Moser. Neuron 83, 1389 (2014).

[2]    A.B. Wong, M.A. Rutherford, M. Gabrielaitis, T. Pangrsic, F. Goettfert, T. Frank, S. Michanski, S. Hell, F. Wolf, C. Wichmann, T. Moser. The EMBO Journal 33, 247 (2014).

[3]    T. Pangrsic, M. Gabrielaitis, S. Michanski, B. Schwaller, F. Wolf, N. Strenzke, T. Moser. Proceedings of the National Academy of Sciences 112, E1028 (2015).

Contact:  Fred Wolf 

Members working within this Project:

 Andreas Neef 
 Mantas Gabrielaitis 
 Fred Wolf 

Former Members:

 Nikolai M. Chapochnikov 

Selected Publications:

T. Pangršič, M. Gabrielaitis, S. Michanski, B. Schwaller, F. Wolf, N. Strenzke, and T. Moser (2015).
EF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells
PNAS 112(9):E1028–E1037.

A.B. Wong, M.A. Rutherford, M. Gabrielaitis, T. Pangrsic, F. Göttfert, T. Frank, S. Michanski, S. Hell, F. Wolf, C. Wichmann, and T. Moser (2014).
Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis
EMBO J 33(3):247-264.

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