Michael P. Kilgard Sensory Experience and Cortical Plasticity University of Texas at Dallas

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

40% increase in response strength –1.4 vs. 1.0 spikes per noise burst (p< ) 10% decrease in frequency bandwidth –2.0 vs. 2.2 octaves at 40dB above threshold (p< 0.05) Three decibel decrease in threshold –17 vs. 20 dB ms (p< 0.001) Enriched Standard A1 Enrichment Effects - after 2 months N = 16 rats, 820 sites Stronger, More Selective, and More Sensitive Environmental Enrichment Improves Response Strength, Threshold, Selectivity, and Latency of Auditory Cortex Neurons Environmental Enrichment Improves Response Strength, Threshold, Selectivity, and Latency of Auditory Cortex Neurons Engineer ND, Percaccio CR, Pandya PK, Moucha R, Rathbun DL, Kilgard MP. Journal of Neurophysiology, 2004.

High Low CochleaCortex

High Low CochleaCortex Cortical Map Plasticity

High-density microelectrode mapping technique

Best Frequency Nucleus Basalis Activity Enables Cortical Map Reorganization M.P. Kilgard, M.M. Merzenich, Science 279(5357): , download file download file

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

Differences between A1 and Posterior Auditory Field – submitted

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 Manuscript in preparation

Temporal Processing Typical Response of A1 Neurons to Tone Trains

After Pairing NB Stimulation with 15 Hz Tone Trains

After Pairing NB Stimulation with 5 Hz Tone Trains

N = 15 rats, 720 sites Plasticity of Temporal Information Processing in the Primary Auditory Cortex in the Primary Auditory Cortex M.P. Kilgard, M.M. Merzenich Nature Neuroscience 1(8): , 1998 download file

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% Spatial Variability Leads to Smaller RF’s Temporal Modulation Leads to Larger RF’s Sensory Input Directs Spatial and Temporal Plasticity in Primary Auditory Cortex M.P. Kilgard, P.K. Pandya, J.L. Vazquez, Gehi, A., C.E. Schreiner, M.M. Merzenich Journal of Neurophysiology, 86: , download file download file

How do neural networks learn to represent complex sounds? Spectrotemporal Sequences 100ms20ms High Tone (12 kHz) Low Tone (5 kHz) Noise Burst

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

Context-Dependent Facilitation 100ms20ms High Tone (12 kHz) Low Tone (5 kHz) Noise Burst Number of Spikes ms

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 Order Sensitive Plasticity in Adult Primary Auditory Cortex M.P. Kilgard, M.M. Merzenich Proceedings of the National Academy of Sciences 99: , download filedownload file Schematic Illustration

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 Order Sensitive Plasticity in Adult Primary Auditory Cortex M.P. Kilgard, M.M. Merzenich Proceedings of the National Academy of Sciences 99: , download filedownload file Schematic Illustration

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 Low Tone (5 kHz) Order Sensitive Plasticity in Adult Primary Auditory Cortex M.P. Kilgard, M.M. Merzenich Proceedings of the National Academy of Sciences 99: , download filedownload file Schematic Illustration

Target stimulus (CS+) Add first distractor (CS- 1 ) Add second distractor (CS- 2 ) Add third distractor (CS- 3 ) Task A) Sequence detection B) Frequency discrimination C) Triplet distractor- High first D) Sequence element discrimination E) Triplet distractor- Noise first F) Reverse Order Frequency (kHz) Time (ms) H L N L L LH H H L L L N N N NL N L H H H L N None Map Auditory Cortex Time (months) Operant Training

Discrimination Performance

Differential Plasticity Effects

ExperimentRSRFOnsetSequence Compared with Naïve HLN VERY, VERY Easy Task + (24%)+(10%)+ (0.6ms)More Masking Freq Discrimination Very Easy Task 000Less Masking HLN vs. H, L, N Easy Task ??? -2ms ???Facilitation HLN vs. HHH, LLL, NNN Doable Task + (27%)00Less Masking HLN vs. NNN, LLL, HHH Difficult Task + (30%)- -(12%)- (0.6 ms)More Masking Reverse Discrimination Very difficult Task + (10%) + (1.1 ms)More Masking Exposure Group+ (10%)+ (20%)+ (1.3ms)More Masking Summary Table Frequency Discrimination H, L, N NNNReverse Discrimination HLN vs. NLH Easy Difficult HHHHLN

How do cortical neurons learn to represent speech sounds?

Sash

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

35 %  %  5.3 (p<0.0005)

Sensory Experience Controls: Response Strength Cortical Topography Receptive Field Size Maximum Following Rate Synchronization Spectrotemporal Selectivity

Activity from a single A1 neuron recorded in an awake rat in response to normal and enhanced human speech sounds

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

Training Experiments - Navzer Engineer Amanda Puckett Crystal Novitski Enrichment Experiments - Navzer Engineer Cherie Percaccio Receptive Field Plasticity - Pritesh Pandya Synchrony Experiments - Jessica Vazquez FM Experiments - Raluca Moucha Speech Experiments - Pritesh Pandya and Acknowledgements: and