Cortical Fine Timing and Behavior

Yang YangProgram in Neuroscience, Stony Brook University

Zador Lab, Cold Spring Harbor Laboratory

Sloan-Swartz Meeting 2010, Yale

Precise stimulus timing can guide behavior

∆t ≈ 10 µs

interaural time difference

Not Cortical

Neurons in Auditory Cortex can fire precisely in response to sound

rat

Hromadka, Deweese & Zador, 2008

200 300

monkey

Barbour & Wang, 2003

Cortical fine timing and behavior

Precise stimulus timing can drive behavior Not cortical

Sensory stimuli can elicit precisely timed spikes in cortex

behaviorally relevant?

Can precise cortical spike timing drive behavior? Hard-wired or use-dependent?

Using artificially induced, precisely timed cortical spikes to drive behavior

Behavioral paradigm: 2-Alternative Forced Choice task.

t = 0 LEFT t > 0 RIGHT

2-Alternative Choice TaskQuickTime™ and aYUV420 codec decompressor

are needed to see this picture.

Using artificially induced, precisely timed cortical spikes to drive behavior

Behavioral paradigm: 2-Alternative Forced Choice task. Implant 2 electrodes (A & B, 1.1mm apart) chronically into left

auditory cortex,directly stimulate A and B Task: simultaneous A&B vs. B-∆t-A

t = 0 LEFT t > 0 RIGHT

Spike timing of 3 ms in auditory cortex can drive behavior!

Yang, DeWeese, Otazu, Zador, Nat. Neurosci, 2008

Inter-stimulus Interval (ms)

Spike timing of 3 ms in auditory cortex can drive behavior

100 35 15 7 5 3 10

0.2

0.4

0.6

0.8

1.0

Inter-stimulus interval (ms)

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22/24

11/13 6/85/7

10/15

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Population summary

Spike timing of 3 ms in auditory cortex can drive behavior

Is auditory cortex unique?

YES: Auditory cortex is different from visual cortex

Audition Vision

Sunrise, Monet

fast slow

NO: auditory cortex and visual cortex are similar

Douglas & Martin, 2004

Canonical Circuit

Hromadka et. al, 2005

A1

MT

Buracas et. al, 1998

Physiology

brainmaps.org

A1

V1

What about visual cortex?

Your guess?

Limit in V1 is 15 ms

visual cortex stimulation

7/10

4/4 5/5

2/6

0/7

Visual Cortex is slower than Auditory Cortex

Auditory cortex stimulation

Threshold:Auditory cortex: 1-3 msVisual cortex: 5-15ms

100 35 15 7 5 3 10

0.2

0.4

0.6

0.8

1.0

Inter-stimulus interval (ms)

Fra

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n of

rat

s ab

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abo

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22/2411/13 6/8

5/710/15

2/7

0/4

--- A1--- V1

* **

**

*: p<0.05

**: p<0.005

visual cortex stimulation

7/10

4/4 5/5

2/6

0/7

How about barrel cortex?

Arabzadeh E. et. al, 2003

Barrel cortex neurons can respond precisely to a whisker stimulation

Limit in barrel cortex is 1 ms !

6/6 6/6 6/64/6

0/6

--- S1--- A1--- V1

* * *

Thresholds: Barrel Cortex: 1ms Auditory Cortex: 3ms Visual Cortex: 15ms

Different cortical areas are different in fine timing discrimination

Hard-wired or use-dependent?

Audition

fast

Vision

Sunrise, Monet

slow

Whiskers!

faster

Whisker trimming during development changes properties of barrel cortex

anatomy

Fox 1992

imaging

Holtmaat & Svoboda, 2009

physiology

Glazewski & Fox 1996

Sensory Deprivation

..P0

P60

Control group: non-deprived

..

P0 P60

Control group: ipsilateral

..

P0P60

Experimental group

Performance is impaired for sensory deprived animals

Median performance for each rat on each Inter-stim-inteval.

Barrel controlBarrel deprived

p<0.05: 3,5,15,35,100 (ms)

Comparing all experimental groups

Median performance for each rat on each Inter-stim-inteval.Error bar: median absolute deviation from the median

--- Barrel--- Auditory--- Visual--- Deprived

Performance improved for sensory deprived animals with training

y=0.5+(k-0.5)*(1-exp(-t/tau)) k: asymptotic performance, tau: time constant

Tau is bigger for deprived animals than for control animals

p=0.0013

Conclusions The ability to exploit timing information

behaviorally is use-dependent Sensory deprived animals were severely impaired in

cortical timing discrimination, suggesting that sensory input during development is essential in establishing the ability of fine timing discrimination in the cortex

Sensory deprived animals showed more improvement with training than the control animals, suggesting that sensory deprived animals could learn to use the cortical timing cue with direct cortical stimulation input

Future directions…

Many thanks to… Tony Zador Mike DeWeese Gonzalo Otazu

Past and present Zadorians

My dear rats yy001-yy293