Neuronal Computationin the Auditory System

Matthew A. Xu-Friedman

641 Cooke Hall

645-2363 x202

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

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

AuditoryNerve

Bushy Cell

from Ryugo & Fekete (1982)

20 µm

Jitter Reduction in Auditory Brainstem

0 10 20 30 ms

0 10 20 30 ms

from Joris et al. (1994)

2 ms

Voltage clamp

2 nA

Current clamp0

–30

–60

Vm (

mV

)

2 ms

MouseP16–21, 34°

Auditory Nerve Synapses onto Bushy Cells Are Powerful

20 ms

2 nA

0

–30

–60

Vm (

mV

)

Mimicking Auditory Nerve Inputs with Dynamic Clamp

Stim

ANs

–30

–60

2 ms

10 nS

N = 1Synaptic Conductance

Membrane Potential

N = 4

Jitter Reduction with Multiple Inputs

1 ms

500 spikes/s

12

4

3

1

0

SD

ou

t (m

s)41 # Inputs

N = 1

2

3

4

1 ms

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

QuestionWhat 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

Cerebellar Synapses

MossyFiber

GranuleCell

PurkinjeCell

ClimbingFiber

from Palay & Chan-Palay (1974)

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

Electron Microscopy of Climbing Fibers

0.5 m

Serial Electron Microscopy

Mossy Fiber Synapses Are Densely Packed, Without Intervening Glia

Climbing Fiber Mossy Fiber

ConclusionDense 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