Dr. Matthew Xu-Friedman - Department of Biological Sciences

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

Synaptic Transmission

Ca2+

EPSP + action potential EPSC

• How is synaptic transmission affected by activity? • Mechanism • Functional consequences

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

Experimental Setup

Slice Recording

Stimulate Record

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

Effects of Activity 100 Hz 20 ms

200

2 nA

10 ms

333 6 ms

• 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?

Voltage clamp P15–21 mice 34°C

Synaptic Variance *

*

Hua Yang

*

1 nA 0.1 s

• Synaptic transmission has both stochastic (random) and deterministic (predictable) components • How does randomness affect transmission of information? • Is it disruptive? 50 Hz Poisson

Effects of Randomness Conductance (nS)

• Mimic random and nonrandom 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

0

20 Pulse number

40 mV

40

100 Hz 50 ms Yang & X-F (in press)

Auditory Experience Tenzin Ngodup

Normal

Noise-reared

*

EPSC2/EPSC1

Dt

Xiaowen Zhuang

2 nA 10 ms

1

0 0.001

0.01

0.1 Dt (s)

• 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?

1

Action Potential Initiation Yang Yang

Vm (mV)

Typical Neuron dendrites

0

–60

dVm/dt (V/ms)

0.5 s

20 ms

0.5 ms

0.2

0.5 ms

soma

0 –0.2

–60

0 Vm (mV)

• • • • •

Bushy cell

axon

–60

0 Vm (mV)

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

Acknowledgements Jack Goetz Tenzin Ngodup

Hua Yang Xiaowen Zhuang

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

Yang Yang