Neuronal Computationin the Auditory Brainstem

Matthew A. Xu-Friedman

Dept. Biological Sciences

Synaptic Transmission

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

Ca2+

EPSP + action potential

EPSC

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

• 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 clampP15–21 mice34°C

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

Hua Yang

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

0Conduct

ance

(nS)

40200Pulse number

100 HzYang & X-F (in press)50 ms 40 mV

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/E

PSC

1

0.001 0.01 0.1 1Dt (s)

Tenzin Ngodup Xiaowen Zhuang

10 ms

2 nA

Dt

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

–0.2dV

m/dt

(V/m

s)

–60 0Vm (mV)

0.5 ms

Typical Neuron

–60

0

Vm (

mV

)

0.5 s

–60 0Vm (mV)

Bushy cell

20 ms 0.5 ms

dendrites

soma

axon

Yang Yang

AcknowledgementsFormer 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)

CollaborationsRichard Salvi, Center for Hearing and

DeafnessMicheal Dent, PsychologyTobias Moser & Andreas Neef,

Göttingen

FundingNIDCDNSF IOS 1208131

Tenzin Ngodup

Xiaowen Zhuang

Yang Yang

Jack Goetz

Hua Yang