Synaptic homeostasis hypothesis synaptic depression during sleep
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This document discusses evidence from a study investigating changes in miniature excitatory postsynaptic currents (mEPSCs) in the frontal cortex of mice and rats depending on their sleep/wake state. The study found that mEPSC frequency and amplitude increased after waking and decreased after sleep, suggesting that synaptic strength is potentiated with wakefulness and depotentiated during sleep. Sleep deprivation increased mEPSCs, while recovery sleep decreased them, supporting the hypothesis that sleep facilitates synaptic downscaling. The results provide direct evidence that sleep plays a role in remodeling synapses in the brain.
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Synaptic homeostasis hypothesis synaptic depression during sleep
- 1. Alteration in Cortical mEPSCs Depending on Sleep/ Wake Evidence for Synaptic Remodeling in Sleep CSB445: Kathleen Harrison
- 2. The problem Evidence to support wake being associated to synaptic potentiation and sleep with depression. Great interest in this hypothesis: however, there are still areas of support lacking direct proof for changes in synaptic alteration. >1600 Papers >1000 Citations 600 Citations On sleep and the synapse after 2003 On Tononi & Cirelli s 2003 paper 45 Papers On sleep and the synapse before 2003 On Tononi & Cirelli s 2006 paper
- 3. Remember: (Wong, Y. 2015) (1) Wakefulness is associated with synaptic potentiation in cortical circuits; (2) Synaptic potentiation is tied to the homeostatic regulation of NREM sleep EEG slow wave activity; (3) Slow wave activity is associated with synaptic downscaling; (4) Synaptic downscaling is tied to the beneficial effects of sleep on neural function and, indirectly, on performance (Tononi & Cirelli, 2003)
- 4. Why? >25% Calories used in the brain But only ~2% of mass 4.7 x 109 ATP/ neuron/ second
- 5. Support for the Model Neuronal (Vyazovskiy et al., 2008) Structural Electrical Synaptic 40% AMPAr post wake/ sleep Molecular (Bushey, Tononi, Cirelli. 2011) # & density post wake/ sleep firing rates post wake/ sleepevoked AP post wake/ sleep (Vyazovskiy et al., 2008) (Vyazovskiy et al., 2009)
- 6. Hypothesis: Miniature EPSCs (mEPSCs) from frontal cortex slices of mice and rats Awake or asleep should show changes in frequency and amplitude of mEPSCs Increased after waking and decreased after sleep, independent of time of day Sleep Deprivation and recovery sleep should increase, and decrease mEPSCs respectively
- 7. Looking for Change: Pre/Post Synapse Vesical (Quanta) Release Frequency AMPAr Trafficking & Scaffold remodeling
- 8. Experiments Sleep VS Wake Cortex harvested when awake, or asleep - mSPSCs Sleep Deprived Cortex harvested at same time, but one group awake, Sleep Recovery Cortex harvested at same time, but one group given recovery Sleep in Other Models Cortex harvested from mice after sleep deprivation
- 10. How it works Step 1 Isolate Cortex => Neuron Step 2 Voltage Clamp Whole cell clamp Step 3 Record & Analyze mESPCs: Hz & pA
- 11. Experiments Sleep VS Wake Cortex harvested when awake, or asleep - mSPSCs Sleep Deprived Cortex harvested at same time, but one group awake, Sleep Recovery Cortex harvested at same time, but one group given recovery Sleep in Other Models Cortex harvested from mice after sleep deprivation
- 12. Experiments Sleep VS Wake Cortex harvested when awake, or asleep - mSPSCs Result: Presynaptic - Higher frequency of NT release Postsynaptic - Increase in amplitude (Liu et al. 2010)
- 13. Experiments Result: Presynaptic - Higher frequency of NT release Postsynaptic - Increase in amplitude Sleep Deprived Cortex harvested at same time, but one group awake, (Liu et al. 2010)
- 14. Experiments Result: Presynaptic - Decreased frequency of NT release Postsynaptic - Decrease in amplitude Sleep Recovery Cortex harvested at same time, but one group given recovery (Liu et al. 2010)
- 15. Experiments Result: Presynaptic - Increased frequency of NT release Postsynaptic - Increase in amplitude Sleep in Other Models Cortex harvested from mice after sleep deprivation (Liu et al. 2010)
- 16. Conclusion: Found that Hz and pA of mEPSCs increased after waking, decreased after sleep Independent of time of day Recovery sleep decreased mEPSCs Hz and pA Suggest sleep facilitates synaptic depotentiation Stronger synapses require more energy, space, and supplies: generalized renormalization of synapses may be an important function of sleep. (Liu et al. 2010)
- 17. Pros Contradictory results when scaled? Importance of checking data! Cons Good Evidence for SHY Good area of investigation Strengths of hypothesis Variation in mEPSP post SD mEPSP post SD same as wake/ control?
- 18. References: Bushey, Tononi, Cirelli. (2011) Sleep and Synaptic Homeostasis: Structural Evidence in Drosophila Liu ZW, Faraguna U, Cirelli C, Tononi G, Gao XB. (2010) Direct Evidence for Wake-Related Increases and Sleep-Related Decreases in Synaptic Strength in Rodent Cortex VyazovskiyVV, CirelliC,Pfister-GenskowM,FaragunaU,TononiG (2008) Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep. Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, Cirelli C, Tononi G (2009) Cortical firing and sleep homeostasis.
- 19. Questions?