Activation of extracellular signal-related kinase signaling in the pedunculopontine tegmental cells is involved in the maintenance of sleep in rats

In paper citation: (Desarnaud, Macone & Datta, 2011)

The new results from this paper include:

1. Levels of ERK 1&2 expression and phosphorylation in the PPT increased with the amount of time spent in sleep. It did not increase in the mPRF or the cortex.
2. With increased time spent sleeping, levels of ERK 1&2 activity increased in the PPT and decreased in the mPRF.
3. Levels of ERK 1&2 expression, phosphorylation, and activity in the PPT of individual animals positively correlated with the total percentage of time spent in SWS, REM, and total sleep. 
4. Levels of ERK 1&2  expression, phosphorylation, and activity in the PPT of individual animals negatively correlated with their total percentage of time spent awake.

Other important information:

• ERK 1&2 are cytoplasmic until activated. Then they translocate to the nucleus and activate cAMP response element binding protein (Vanhoutte et al. 1999).
• Other studies have shown that activating ERK 1&2 increases sleep in a dose dependent manner, and blocking ERK 1&2 decreases sleep (Foltenyi et al. 2007).
• Figure 7 of the paper describes an entire model of ERK 1&2's involvement in sleep.
• In wakefulness 
• glutamate activity is high enough to activate NMDA receptors (not just kainate receptors)
• Ca2+ rushes in and activates STEP, a phosphatase
• STEP dephosphorylates ERK 1&2
• Ca2+ also activates CaMK2
• In SWS
• GABA activates GABA-b receptors, which are linked to G proteins
• the G proteins inhibit adenylyl cyclase, and CaMK2
• This allows ERK 1&2 and PKA to increase
• In REM sleep
• Glutamate activates kainate receptors
• These let in just a little Ca2+ increasing ERK 1&2
• The Ca2+ activates AC and increases PKA 

Remaining questions:

• Why did they only study the first two hours of sleep? Did it have to do with initial ERK levels being different from later ERK levels? How long does it take ERK to clear?
• This study splits rats into low sleepers and high sleepers. What might cause a rat to sleep less in the first place and could this be correlated to the findings that we see?
• Why do they use phosphorylated myelin basic protein to measure ERK activity levels?