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