1. What is sleep for? Sleep and Neural Function July 6 th , 2007

2. An embarrassment of riches? Immune Function Muscle/organ Function Toxin Removal Energy Repletion Somatic Regeneration Neural Regeneration Predator Avoidance Brain Cooling Brain Development Learning and Memory Species Programming Psychological Function Ok, so maybe it does lots of things…who cares? ??????? ???????

3. Neuroscience and developmental biology are incomplete without an understanding of sleep function

4. Ethology is incomplete without an understanding of sleep function

5. Sleep medicine is incomplete without an understanding of sleep function

7. Sleep is regulated and animals die in the absence of sleep

8. So why haven’t we figured it out?

9. Problem 1: Evolution and Adaptation

10. Is human sleep an accumulation of functions? 1 O Function 2 O Function 3 O Function 4 O Function 5 O Function 6 O Function 7 O Function 9 O Function 8 O Function nematodes arthropods chordates From Raizen, 2007

11. Problem 2: distinguishing function from interaction

12. Problem 3: disentangling sleep from the clock Dijk and Schantz, 2005 ; Fuller et al., 2006; Zvonic, et al., 2007

13. First things first: we don’t sleep ‘cause there’s nothing else to do

15. Clues from ontogeny: sleep is maximal when the brain is growing and very plastic Adapted from Roffwarg et al., 1966; Jouvet-Mounier, 1970 REM NREM

17. Clues from molecular biology – transcription Guzman-Marin et al 1997

18. Nakanishi et al 1997 Clues from molecular biology – translation

20. A function that is simple and conserved ? Species Specific & Specialized Adaptations Species Specific & Specialized Adaptations Common Function ?

21. Do gifted and talented mollusks sleep to learn? Brown et al., 2006

23. So, do all species sleep to learn, or remember?

24. What people can tell us that other animals can’t... Stickgold et al., 2000

26. insights from big brains.. Huber et al., 2004

33. What kind of activity is necessary? Chronic neuronal recording

34. Scalar measures and relation to sleep stage

37. Cortical plasticity triggered by MD: Optical maps Non-deprived eye Deprived eye

38. Cortical plasticity triggered by MD: Unit physiology MD Normal: cortical neurons driven by both eyes MD: most neurons driven by non-deprived eye right eye left eye Both eyes

40. Sleep enhances loss of function in deprived eye pathways

41. Sleep-dependent plasticity requires cortical activity in sleep Modified from Hata and Stryker 1994; Frank et al., 2006

42. What we know so far—and what we suspect. Sleep Enhances ODP Activity- dependent CREB pathways? NMDA, AMPA VGCCs, GABA? PKA, cAMKII ERK Calcineurin? Genes up? Genes down? Protein synthesis? ECM? Changes in spines? Activity changes Thalamo- cortical? Intra- cortical? Intrinsic or Network? Excitatory /inhibitory? REM sleep? NREM sleep?

43. [email_address] 112 Johnson Pavilion Dept. of Neuroscience University of Pennsylvania Philadelphia PA 19104 Dr.’s Naoum Issa and Michael Stryker Dr. Sushil Jha: Reversible inactivation, chronic recording Dr.‘s Sara Aton and Julie Seibt: NMDAR-protein synthesis Past graduate students: Brian Jones, Laila Dadvand Students: Nick Steinmetz Lab technician: Tammi Coleman