Alteration in Cortical mEPSCs Depending on Sleep/ Wake
Evidence for Synaptic Remodeling in Sleep
CSB445: Kathleen Harrison
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 PapersOn sleep and the synapse before 2003
On Tononi & Cirelli’s 2006 paper
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)
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/ sleep evoked AP post wake/ sleep
(Vyazovskiy et al., 2008)
(Vyazovskiy et al., 2009)
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
Looking for Change: Pre/Post Synapse
Vesical (Quanta) Release FrequencyAMPAr Trafficking & Scaffold remodeling
Experiments
Sleep VS WakeCortex harvested when awake, or asleep - mSPSCs
Sleep Deprived Cortex harvested at same time, but one group awake,
Sleep RecoveryCortex harvested at same time, but one group given recovery
Sleep in Other ModelsCortex harvested from mice after sleep deprivation
How it works
Step 1
Isolate
Cortex => Neuron
Step 2
Voltage Clamp
Whole cell clamp
Step 3
Record & Analyze
mESPCs: Hz & pA
Experiments
Sleep VS WakeCortex harvested when awake, or asleep - mSPSCs
Sleep Deprived Cortex harvested at same time, but one group awake,
Sleep RecoveryCortex harvested at same time, but one group given recovery
Sleep in Other ModelsCortex harvested from mice after sleep deprivation
Experiments
Sleep VS WakeCortex harvested when awake, or asleep - mSPSCs
Result:Presynaptic - Higher frequency of NT release Postsynaptic - Increase in amplitude
(Liu et al. 2010)
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)
Experiments
Result:Presynaptic - Decreased frequency of NT release Postsynaptic - Decrease in amplitude
Sleep RecoveryCortex harvested at same time, but one group given recovery
(Liu et al. 2010)
Experiments
Result:Presynaptic - Increased frequency of NT release Postsynaptic - Increase in amplitude
Sleep in Other ModelsCortex harvested from mice after sleep deprivation
(Liu et al. 2010)
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)
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?
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.