Neuronal Computation in the Auditory System Matthew A. Xu-Friedman 641 Cooke Hall 645-2363 x202.
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Transcript of Neuronal Computation in the Auditory System Matthew A. Xu-Friedman 641 Cooke Hall 645-2363 x202.
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