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Neuronal Computation in the Auditory System

Neuronal Computation in the Auditory System. Matthew A. Xu-Friedman. 641 Cooke Hall 645-2363 x202. Question. How are cells in the brain specialized to carry out behaviorally relevant computations?. Approaches. Identify computations carried out in vivo

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Neuronal Computation in the Auditory System

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  1. Neuronal Computationin the Auditory System Matthew A. Xu-Friedman 641 Cooke Hall 645-2363 x202

  2. Question How are cells in the brain specialized to carry out behaviorally relevant computations? Approaches • Identify computations carried out in vivo • Use brain slice recordings to characterize cells and synapses • Determine which properties are critical to in vivo behavior

  3. Mammalian Auditory System • Analyzing and localizing sounds • Requires precise temporal information • Encoded in precise timing of neuronal activity (spikes) • Synapses are specialized to preserve and improve temporal information

  4. from Joris et al. (1994) 0 10 20 30 ms 0 10 20 30 ms Jitter Reduction in Auditory Brainstem Auditory Nerve Bushy Cell 20 µm from Ryugo & Fekete (1982)

  5. 0 –30 Vm (mV) 2 ms –60 0 –30 Vm (mV) 2 nA –60 20 ms Auditory Nerve Synapses onto Bushy Cells Are Powerful Voltage clamp Current clamp 2 nA 2 ms Mouse P16–21, 34°

  6. N = 1 N = 4 Synaptic Conductance 10 nS Membrane Potential –30 2 ms –60 Mimicking Auditory Nerve Inputs with Dynamic Clamp Stim ANs

  7. 4 3 2 500 spikes/s 1 1 ms 1 SDout (ms) 0 1 4 # Inputs Jitter Reduction with Multiple Inputs N = 1 2 1 ms 3 4

  8. Conclusion Suprathreshold inputs can contribute to significant jitter reduction, even when the number of inputs is low. Future Plans • Higher rates of activity • Neuromodulators • More realistic firing patterns • Development

  9. Question What is the relationship between a synapse’s structure and its functional and physiological properties? Approaches • Study synaptic properties using brain slices • Study anatomy using electron microscopy • Compare synapses with different properties

  10. Cerebellar Synapses Granule Cell Purkinje Cell Mossy Fiber Climbing Fiber from Palay & Chan-Palay (1974)

  11. Cyclothiazide Receptor Desensitization Contributes to Depression at Mossy Fibers Control Mossy Fiber 25 pA Xu-Friedman & Regehr (2003) 10 ms Climbing Fiber Dittman & Regehr (1998)

  12. Electron Microscopy of Climbing Fibers 0.5 m

  13. Serial Electron Microscopy

  14. Mossy Fiber Synapses Are Densely Packed, Without Intervening Glia Climbing Fiber Mossy Fiber

  15. Conclusion Dense packing of mossy fiber release sites can lead to receptor desensitization and depression Future Plans • Can ultrastructure explain other features of synapses, such as facilitation? • Electron tomography

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