PERCEPTUAL LEARNING AND CORTICAL SELF-ORGANIZATION Mike Kilgard University of Texas Dallas

PERCEPTUAL LEARNING AND CORTICAL SELF-ORGANIZATION What aspects of experience guide learning and plasticity ?

55% increase in response strength –1.4 vs. 0.9 spikes per noise burst (p< ) 22% decrease in frequency bandwidth –1.8 vs. 2.2 octaves at 30dB above threshold (p< ) One millisecond decrease in latency –15.8 vs ms (p< 0.005) Two decibel decrease in threshold –17 vs. 19 dB ms (p< 0.01) Enriched Standard A1 Enrichment Effects - after 2 months N = 16 rats, 820 sites Journal of Neurophysiology, 2004 Stronger, Faster, More Selective, and More Sensitive

Time Course Role of Exercise Role of Behavioral Context Role of Neuromodulators Cellular Mechanism Role of Attention Open Questions

20±10 vs. 75±20 μV 81±19 vs. 37±20 μV Red Group EnrichedBlue Enriched Environmental Enrichment 22 rats total

12 rats per group Plasticity Index 1X 2X Enriched  Standard  NB Lesion Enriched  NB Lesion Standard  Sham Enriched  Sham Standard  Exercise  Social  Auditory Exposure 

Time Course Role of Exercise Role of Social Interactions Role of Acetylcholine Cellular Mechanism Role of Attention Open Questions

Action potentials also adapt more readily in enriched rats compared with standard rats

Time Course Role of Exercise Role of Behavioral Context Role of Acetylcholine Possible Cellular Mechanism Role of Attention Open Questions

21 % increase in response strength –1.26 vs spikes per noise burst (p< ) 13 % decrease in frequency bandwidth –1.87 vs octaves at 40dB above threshold (p< ) 1.8 millisecond decrease in minimum latency –14.84 vs ms (p< 0.01) 4.6 decibel decrease in threshold –15.2 vs dB (p< ) Operant Effects - after 2 months of 2 hours/day training N = 42 rats, 2,231 sites Stronger, Faster, More Selective, and More Sensitive

LEARNING MOTIVATION

PLASTICITY? MOTIVATION

100ms 20ms High Tone (12 kHz) Low Tone (5 kHz) Noise Burst Unpaired background sounds CS+ CS-’s Task Schematic

EASY DIFFICULT Sequence Discrimination vs. Elements Silence TRAINING DAYS High Low Noise HLN (CS+) Frequency Discrimination Low (CS+) High Silence TRAINING DAYS Sequence Discrimination vs. Triplets - High first HHH LLL NNN Silence TRAINING DAYS HLN (CS+) Sequence Discrimination vs. Triplets - Noise first NNN LLL HHH Silence TRAINING DAYS HLN (CS+) Sequence Order Discrimination TRAINING DAYS NLH Silence HLN (CS+) Sequence Detection HLN (CS+) Silence TRAINING DAYS

Frequency Discrimination Low (CS+) High Silence TRAINING DAYS Sequence Discrimination vs. Triplets - High first HHH LLL NNN Silence TRAINING DAYS HLN (CS+) Sequence Discrimination vs. Triplets - Noise first NNN LLL HHH Silence TRAINING DAYS HLN (CS+) Sequence Order Discrimination TRAINING DAYS NLH Silence HLN (CS+) EASY DIFFICULT

Experimental groups# Rats # A1 Sites A) Naïve controls7329 B) Sound Exposure (HLN, NNN, LLL, HHH)4263 C) HLN Detection4251 D) HLN vs. H L, or N4253 E) Freq Discrimination Group (LLL vs. HHH)8444 F) HLN vs. HHH, LLL, NNN4189 G) HLN vs. NNN, LLL, HHH7433 H) Reverse Discrimination (HLN vs. NLH)5329 Totals43~2,500 Project Summary

HLN Detection Frequency Discrimination HLN vs. HHH, LLL, NNN HLN vs. H, L, N HLN vs. NNN, LLL, HHH HLN vs. Reverse Group #

Time Course ~ Weeks Role of Exercise Insignificant Role of Social Contact Insignificant Role of Behavioral Context Important Role of Acetylcholine Not Required Cellular Mechanism Long-Term Potentiation? Role of Task Difficulty Important Influences on Cortical Plasticity

Behavioral Relevance Neural Activity - Internal Representation External World -Sensory Input Neural Plasticity - Learning and Memory

Enrichment A1 Experiments - Navzer Engineer Enrichment Evoked Potentials - Cherie Percaccio Behavioral Training - Navzer Engineer Crystal Novitski Acknowledgements: and

Behavioral Relevance Neural Activity - Internal Representation External World -Sensory Input Neural Plasticity - Learning and Memory Plasticity Rules - Educated Guess Behavioral Change

Best Frequency Science, 1998

Tone Frequency - kHz Frequency-Specific Map Plasticity N = 20 rats; 1,060 A1 sites

Nature Neuroscience, 1998 N = 15 rats, 720 sites

Journal of Neurophysiology, 2001 N = 13 rats, 687 sites Temporal Plasticity is Influenced by Carrier Frequency

Stimulus Paired with NB Activation Determines Degree and Direction of Receptive Field Plasticity Frequency Bandwidth Plasticity N = 52 rats; 2,616 sites

Frequency Bandwidth is Shaped by Spatial and Temporal Stimulus Features Modulation Rate (pps) Tone Probability 15% 50 % 100% Journal of Neurophysiology, 2001 Spatial Variability Leads to Smaller RF’s Temporal Modulation Leads to Larger RF’s

58% of sites respond with more spikes to the noise when preceded by the high and low tones, compared to 35% in naïve animals. (p< 0.01) Context-Dependent Facilitation - Group Data 100ms20ms Low Tone (5 kHz) Noise Burst High Tone (12 kHz) N = 13 rats, 261 sites Proceedings of the National Academy of Sciences, 2002

25% of sites respond with more spikes to the low tone when preceded by the high tone, compared to 5% of sites in naïve animals. (p< 0.005) Context-Dependent Facilitation - Group Data Low Tone (5 kHz) 100ms20ms High Tone (12 kHz) Low Tone (5 kHz) Noise Burst N = 13 rats, 261 sites Proceedings of the National Academy of Sciences, 2002

10% of sites respond with more spikes to the high tone when preceded by the low tone, compared to 13% of sites in naïve animals. Context-Dependent Facilitation - Group Data 100ms20ms Noise Burst High Tone (12 kHz) High Tone (12 kHz) N = 13 rats, 261 sites Proceedings of the National Academy of Sciences, 2002 Low Tone (5 kHz)

Naïve Control 1 Day Post 10 Day Post 20 Day Post All Groups Percent of Cortex Responding to 21 kHz at 40 dB * = p< 0.05 ** = p< 0.01 * * * ** Tone Frequency (kHz)

High frequency map expansion, p <0.01 Decreased bandwidth (30 dB above threshold) –3.0 vs. 3.6 octaves, p<0.001 Shorter time to peak –56 vs. 73 ms, p<.01 Plasticity in Posterior Auditory Field N = 12 rats; 396 PAF sites

Sash

‘SASH’ Group - Spectrotemporal discharge patterns of A1 neurons to ‘sash’ vocalization (n= 5 rats) kHz

Sash

35 %  %  5.3 (p<0.0005) Tone Frequency (kHz)

Time  Frequency  Example Speech Stream

Sash

Spectrotemporal Sequences 100ms20ms High Tone (12 kHz) Low Tone (5 kHz) Noise Burst Time  Frequency 

METHODS Stimulating Electrode Location from Bregma: 3.3 mm Lateral 2.3 mm Posterior 7.0 mm Ventral Location of reference points used to record EEG activity prior, during and after each stimulation. This information was used to confirm the efficacy of NB activation

NUCLEUS BASALIS ACTIVATION EEG Desynchronization Caused by NB Stimulation EEG VOLTAGE (mV) TIME (msec) The stimulation currents levels ( μAmps) were individually established to be the minimum necessary to briefly desyncronize the EEG during slow wave sleep. The stimulation consisted of a train of twenty biphasic pulses (100 Hz, 0.1 msec pulse width) 19 kHz 50dB 250 msec duration

Behavioral Relevance Neural Activity - Internal Representation External World -Sensory Input Neural Plasticity - Learning and Memory NB stimulation

Paired w/ NB stimulation for a month 100ms20ms High Tone (12 kHz) Low Tone (5 kHz) Noise Burst Unpaired background sounds }

25% of sites respond with more spikes to the low tone when preceded by the high tone, compared to 5% of sites in naïve animals. (p< 0.005) 10% of sites respond with more spikes to the high tone when preceded by the low tone, compared to 13% of sites in naïve animals. 58% of sites respond with more spikes to the noise when preceded by the high and low tones, compared to 35% in naïve animals. (p< 0.01) Context-Dependent Facilitation - Group Data N = 13 rats, 261 sites Proceedings of the National Academy of Sciences, ms20ms High Tone (12 kHz) Low Tone (5 kHz) Noise Burst

Nature Neuroscience, 1998 N = 15 rats, 720 sites

How do cortical networks learn to represent complex sounds? FM sweeps Frequency 160ms

Frequency Time NB Stim. FM Sweep paired with NB stimulation (8 to 4 kHz in 160 ms) No map expansion No preference for downward vs. upward FM sweeps Decreased threshold by 3 dB and latency by 2 ms, and increased RF size by 0.2 octaves only in the region of the frequency map activated by sweep (p<0.01)

Frequency Time NB Stim. FM Sweeps paired with NB stimulation Five downward sweeps of one octave in 160 ms No significant plasticity

Frequency Time NB Stim. Does acoustic context influence plasticity? Five downward sweeps of one octave in 160 ms plus unpaired upward (160 ms) and downward (40 or 640 ms) sweeps Decreased threshold by 4dB and latency by 2ms, and increased RF size by 0.2 octaves all across map (p<0.01) No preference for downward vs. upward FM sweeps Preference for 160 ms long sweeps (p<0.001)

12 rats per group Plasticity Index 1X 2X