Translating Plasticity Research into Clinical Practice

Sensory Experience Alters Response Strength, Selectivity

and Temporal Processingof Auditory Cortex Neurons

Mike KilgardUniversity of Texas at Dallas

• Pioneering experiments by Hubel and Wiesel, Merzenich, Weinberger, Greenough, and many others have shown that cortical circuits are highly adaptive.

• Neural plasticity is likely involved in perceptual learning, development, and recovery from brain injury.

Cochlea CortexTone Frequency

Act

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15 Word Speech Stream >1045 possibilities

Techniques used to study how complex sounds alter cortical processing

Behavioral Nucleus Basalis Environmental Training Stimulation Enrichment

Environmental enrichment increases:• Brain weight

• Gene expression

• Cortical thickness

• Dendritic branching

• Acetylcholinesterase levels

• Oligodendrocyte to neuron ratio

• Number of synapses per neuron

What are the physiological consequences of these anatomical changes?

20±10 vs. 75±20 μV 81±19 vs. 37±20 μV

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22 rats total

Journal of Neurophysiology, 2004

Environmental Enrichment

• Rapid

• Dramatic

• Reversible

• No critical period

Environmental Enrichment

• State dependent?• Other response properties change?• Consequences for speech processing?• What aspects of enrichment are required?

– Exercise– Social– Sensory

• Cellular mechanisms?

High-density Microelectrode

Mapping

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Plasticity in Primary Auditory Cortex

• 40% increase in response strength– 1.4 vs. 1.0 spikes per noise burst (p< 0.00001)

• 10% decrease in frequency bandwidth– 2.0 vs. 2.2 octaves at 40dB above threshold

(p< 0.05)

• 3 dB decrease in threshold– 17.2 vs. 20 dB (p< 0.001)

Enrichment effects persist under general anesthesia

n = 16 rats, 820 A1 sitesJournal of Neurophysiology, 2004

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Consequences for speech processing?

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Enrichment IncreasesPaired Pulse Depression

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• Response of Neurons at a Single Site to Repeated Tones

• Group Average

Enriched housing alters temporal processing

Decrease in best rate by 1.1 Hz in enriched rats7.8 vs. 6.7 Hz (p< 0.001)

Environmental Enrichment

• Rapid

• Dramatic

• Reversible

• No critical period

• Alters temporal processing

Why?

WA

TE

Ra

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Exercise can cause:• A persistent firing pattern in the rat hippocampus,

known as theta-rhythm• Increased release of brain-derived neurotrophic factor

and other growth factors• Changes in gene regulation • Increased cell proliferation and neurogenesis in the

adult mouse dentate gyrus

No ef

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Social Interactions can:• enhance some forms of learning• alter stress hormones• improve recovery from brain damage

Auditory Exposure Enriched Auditory Environment

Nucleus Basalis and Plasticity• Nucleus basalis neurons are activated by

any arousing stimuli.

• Cholinergic agonists and NB stimulation

increase plasticity.

• Cholinergic antagonists and NB lesions

prevent many forms of cortical

plasticity.No effect on

evoked potentials

Auditory Enrichment

• Rapid• Dramatic• Reversible• No critical period• Alters temporal processing• Not dependent on nucleus basalis• Not dependent on exercise or social interactions

Time

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Enrichment Evoked Potentials - Cherie Percaccio

Enrichment A1 Experiments - Navzer Engineer

Acknowledgements:

For more information visit: www.utd.edu/~kilgard

Sash

Spectrotemporal discharge patterns of A1 neurons to ‘sash’(n= 12 rats, 445 cortical sites)

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C) 'sash' G) 'sash' - modified

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