1. Neuronal Computation in 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. Auditory Nerve Bushy Cell from Ryugo & Fekete (1982) 20 µm Jitter Reduction in Auditory Brainstem 0102030 ms 0102030 ms from Joris et al. (1994)

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

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

7. Jitter Reduction with Multiple Inputs 1 ms 500 spikes/s 1 2 4 3 1 0 SD out (ms) 41 # Inputs N = 1 2 3 4 1 ms

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

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 Mossy Fiber Granule Cell Purkinje Cell Climbing Fiber from Palay & Chan-Palay (1974)

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

12. Electron Microscopy of Climbing Fibers 0.5  m

13. Serial Electron Microscopy

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