1. Neuronal Computation in the Auditory Brainstem Matthew A. Xu-Friedman Dept. Biological Sciences

2. Synaptic Transmission How is synaptic transmission affected by activity? Mechanism Functional consequences Ca 2 + EPSP + action potential EPSC

3. Mammalian Auditory System Analyzes and localizes sounds Requires precise temporal information Uses precise timing of spikes Preserves and improves temporal information with various adaptations We focus on the synapse formed by auditory nerve fibers onto bushy cells in the cochlear nucleus Endbulb of Held Bushy cell

4. Experimental Setup

5. Slice Recording Stimulate Record

6. Current Projects How does ongoing activity affect synapses? How does auditory experience influence development? How are action potentials initiated with precision?

7. Effects of Activity Depression results from: Vesicle depletion & receptor desensitization (Yang & X-F, 2008; Chanda & X-F, 2010) Consequence Bushy cells respond less reliably after a while What about more realistic conditions? 2 nA 20 ms 10 ms 6 ms 100 Hz 200 333 Voltage clamp P15–21 mice 34°C

8. Synaptic Variance Synaptic transmission has both stochastic (random) and deterministic (predictable) components How does randomness affect transmission of information? Is it disruptive? 0.1 s 1 nA *** 50 Hz Poisson

9. Effects of Randomness Mimic random and non- random synaptic input, by injecting current into the cell With non-random synapse, spiking is very consistent, but some EPSPs consistently fail With random synapse, even small EPSPs can sometimes cause spike Randomness enhances information transmission 150 0 Conductance (nS) 40200 Pulse number 100 Hz Yang & X-F (in press) 50 ms 40 mV

10. Auditory Experience How is the degree of depression set? Does it depend on the animal’s experience? Rear animals in noise & assess changes Reduces depression, and can cause facilitation Starting to look at opposite treatment (ear-plugging) Increases depression Adaptive, homeostatic response? How are responses to real sounds affected? Noise-rearedNormal * 1 0 EPSC 2 /EPSC 1 0.0010.010.11 t (s) 10 ms 2 nA tt

11. Action Potential Initiation Why do bushy cells have very small action potentials? Most neurons have two pools of sodium channels Bushy cells only have one Does this adaptation support precise timing? Developing new electrophysiology tools to study 0.2 0 –0.2 dV m /dt (V/ms) –600 V m (mV) 0.5 ms Typical Neuron –60 0 V m (mV) 0.5 s –600 V m (mV) Bushy cell 20 ms0.5 ms dendrites soma axon Yang

12. Acknowledgements Former Lab Members Soham Chanda, PhD’10 (postdoc, Stanford) Alexander Fischer (grad student, TU Kaiserslautern) Tim Jarsky (Scientist II, Allen Institute) Lioudmila Pliss (NP, private practice) Sangrok Oh, MS’09 (DO, UB SMBS) John Trimper (grad student, Emory) Collaborations Richard Salvi, Center for Hearing and Deafness Micheal Dent, Psychology Tobias Moser & Andreas Neef, Göttingen Funding NIDCD NSF IOS 1208131