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

2. Cortical plasticity depends upon: Sensory experience Behavioral relevance

3. The Cholinergic Basal Forebrain Provides a Diffuse Neuromodulatory Input to the Cortex Nucleus Basalis

4. Exploring the Principles of Cortical Plasticity using: Systematic Variation of Sensory Experience Nucleus Basalis Stimulation to Gate Cortical Plasticity Experience or Instinct Connectivity & Dynamics Plasticity Neural Representation Importance External world

5. NB stimulation is paired with a sound several hundred times per day for ~20 days. Pairing occurs in awake unrestrained adult rats. Stimulation evokes no behavioral response. Stimulation efficacy is monitored with EEG.

6. Extracellular Recordings Detailed Reconstruction of the Distributed Cortical Response

8. Best Frequency Science, 1998

9. Tone Frequency - kHz Nucleus Basalis Stimulation Generates Map Plasticity that is Specific to the Paired Tone N = 20 rats; 1,060 A1 sites

11. Nature Neuroscience, 1998 Temporal Plasticity is Specific to the Paired Repetition Rate N = 15 rats, 720 sites

12. Journal of Neurophysiology, 2001 Carrier frequency variability prevented map expansion and allowed temporal plasticity. N = 13 rats, 687 sites

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

14. Frequency Bandwidth is Shaped by Spatial and Temporal Stimulus Features Modulation Rate (pps) 0 5 10 15 Tone Probability 15% 50 % 100% Journal of Neurophysiology, 2001

15. Neuron 1 Inputs to Neuron A Neuron 2 Receptive Field Overlap Neuron ANeuron B Inputs to Neuron B Spike synchronization and RF overlap are correlated. Brosch and Schreiner, 1999

16. After Map Expansion: ~85% shared inputs After Sharper Frequency Tuning: ~25% shared inputs What is the effect of cortical plasticity on spike synchonization? Before plasticity: ~50% shared inputs Before Plasticity: ~50% shared inputs

17. -50-40 -30-20 -10 0 1020304050 0 200 400 600 800 1000 1200 Number of Intervals Interval (msec) Cross-correlation: TC 0 25C1.MAT x TC 0 25C2.MAT Cross-correlation Shift Predictor Correlation strength = correlation peak in normalized cross-correlation histogram Correlation width = width at half height of correlation peak

18. Experience-Dependent Changes in Cortical Synchronization Map expansion sharpened synchronization –15pps 9kHz tone trains  50% increase in cross-correlation height (p<0.0001)  17% decrease in cross-correlation width (p<0.01) Bandwidth narrowing smeared synchronization –Two different tone frequencies  50% decrease in cross-correlation height (p<0.0001)  22% increase in cross-correlation width (p<0.001) Intermediate stimuli caused no change in synchronization –15pps tone trains with several different carrier frequencies  No change in cross-correlation height or width N = 23 rats; 1,129 sites; 404 pairs

19. Experience-Dependent Changes in Cortical Synchronization (con’t) Broadband ripple stimulus sharpened synchronization –Sinusoidal power spectrum (one cycle / 6kHz )  54% increase in cross-correlation height (p<0.0001)  27% decrease in cross-correlation width (p<0.01) N = 9 rats; 310 sites; 147 pairs

20. Pairing NB stimulation with a spectrotemporal sequence sharpens response discharge coherence.

21. Peak Latency: 15.2 vs. 18.2 ms (p< 0.00001) Difference Naive After HLN N = 13 rats, 450 sites Time to Peak Response (ms) Time (ms) Spikes per Second Sharpened Cortical Response to High-Low-Noise Sequence

22. Increased Population Discharge Coherence

23. Context-Dependent Facilitation

24. 5% of sites in naïve animals respond with more spikes to the 5 kHz tone when preceded by the 12 kHz tone, compared to 25% after sequence pairing. (p< 0.005) 35% of sites in naïve animals respond with more spikes to the noise when preceded by the high and low tones, compared to 58% after sequence pairing. (p< 0.01) 13% of sites in naïve animals respond with more spikes to the 12 kHz tone when preceded by the 5 kHz tone, compared to 10% after sequence pairing. Context-Dependent Facilitation - Group Data N = 13 rats, 261 sites

25. Sensory Experience Controls: Cortical Topography Receptive Field Size Maximum Following Rate Spectrotemporal Selectivity Synchronization

27. 55% increase in response strength –1.4 vs. 0.9 spikes per noise burst (p< 0.0001) 22% decrease in frequency bandwidth –1.8 vs. 2.2 octaves at 30dB above threshold (p< 0.0001) One millisecond decrease in minimum latency –15.8 vs. 16.8 ms (p< 0.005) Two decibel decrease in threshold –17 vs. 19 dB ms (p< 0.01) Increased synchronization –13% increase in cross-correlation height (p< 0.01) Enrichment Effects N = 14 rats, 738 sites

28. Experience or Instinct Connectivity & Dynamics Plasticity Neural Representation Importance External world Rules of Cortical Plasticity

29. Experience or Instinct Connectivity & Dynamics Plasticity Neural Representation Importance External world

30. Experience or Instinct Connectivity & Dynamics Plasticity Behavioral Change Neural Representation Importance External world

33. Spectral Stimuli

34. Temporal Stimuli

35. Rules of Cortical Plasticity

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

37. RF Increase  Increased Synchrony Temporal Task: BF Pairing 15 pps, 9 kHz Tone Width

38. RF Decrease  Decreased Synchrony Spectral Task: BF Pairing 2 Frequencies Randomly Interleaved Width

39. RF Increase  No Change in Synchrony Temporal and Spectral Task: BF Pairing 15 pps Multiple Frequencies Width

40. No Change in RF  Increased Synchrony Spectral-temporal Task: BF Pairing Moving Stimuli (FM’s) Width

41. RF Decrease  Increased Synchrony Complex Spectral Task: BF Pairing Steady State High Density Ripple Width