2. Sensory Experience Alters Response Strength, Selectivity and Temporal Processing of Auditory Cortex Neurons Mike Kilgard University of Texas at Dallas

3. 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 Cortex Tone Frequency Action Potentials

4. Time  Frequency  15 Word Speech Stream >10 45 possibilities

5. Techniques used to study how complex sounds alter cortical processing Behavioral Nucleus Basalis Environmental Training Stimulation Enrichment

7. 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?

8. 20±10 vs. 75±20 μV 81±19 vs. 37±20 μV Red Group EnrichedBlue Enriched 22 rats total Journal of Neurophysiology, 2004

9. Environmental Enrichment Rapid Dramatic Reversible No critical period

10. Environmental Enrichment State dependent? Other response properties change? Consequences for speech processing? What aspects of enrichment are required? –Exercise –Social –Sensory Cellular mechanisms?

11. High-density Microelectrode Mapping

12. Enriched Housing Standard Housing Plasticity in Primary Auditory Cortex

13. 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 sites Journal of Neurophysiology, 2004

14. Time  Frequency  Consequences for speech processing?

15. 200 ms Interstimulus Interval Enrichment Increases Paired Pulse Depression

19. Response of Neurons at a Single Site to Repeated Tones Group Average

20. Enriched housing alters temporal processing Decrease in best rate by 1.1 Hz in enriched rats 7.8 vs. 6.7 Hz (p< 0.001)

21. Environmental Enrichment Rapid Dramatic Reversible No critical period Alters temporal processing Why?

23. 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 effect on evoked potentials

24. No effect on evoked potentials Social Interactions can: enhance some forms of learning alter stress hormones improve recovery from brain damage

25. Auditory Exposure Enriched Auditory Environment

26. 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

27. Auditory Enrichment Rapid Dramatic Reversible No critical period Alters temporal processing Not dependent on nucleus basalis Not dependent on exercise or social interactions

28. Time  Frequency 

29. Enrichment Evoked Potentials - Cherie Percaccio Enrichment A1 Experiments - Navzer Engineer Acknowledgements: For more information visit: www.utd.edu/~kilgard

30. Sash

31. Spectrotemporal discharge patterns of A1 neurons to ‘sash’ (n= 12 rats, 445 cortical sites) Time (msec) Site Number kHz Spikes per second High Low