Single Cell Activity Patterns of Pedunculopontine Tegmentum Neurons Across the Sleep-Wake Cycle in Freely Moving Rats

In paper citation: (Datta & Siwek, 2002)

The new findings in this paper:

• There are three types of cells in the PPT of the rat (from measurements of 70 individual cells):
• ~12.86% of the cells are REM-on cells. These cells are more active during REM sleep than wakefulness or SWS. They start firing 5-10 seconds before the onset of REM and stop firing 5-8 seconds before the end of REM. These cells fire tonically with ISI modes of 90-110ms.
• ~60% of the cells are Wake-REM-on cells. These cells are more active during wakefulness and REM than SWS. They become silent at the onset of SWS and stay silent until 5-8 seconds  before the onset of REM. These cells fire tonically, but their firing rate was lower during REM, dropping from 15Hz (wake) to 10Hz  (REM). 
• ~27.14% of the cells are state-independent.
• There was no evident spatial differentiation within the PPT.
• None of the PPT cells fired in a bursting manner at any time.
• The average duration of spikes was around 1ms for all three types of cells, indicating that they were probably not GABAergic cells (which have spike duration of .5ms) but rather cholinergic cells
• When awake, the 70 cells fired 854 spikes/second. When in SWS, the 70 cells fired 63 spikes/second. When in REM sleep, the 70 cells fired 559 spikes/second. The activity of the cholinergic cells is thus assumed to be about 65% of the wakefulness baseline during REM sleep.

Other important information:

• Glutamate microinjection in the PPT increases the duration of REM sleep in the rat (Datta et al., 2001a)
• Choline microinjection in the PRF induces REM sleep in the rat (Gnadt & Pegram, 1986)
• Thus it is hypothesized that the PPT is a major source of cholinergic input to the PRF that can induce choline agonist-induced sleep
• Aminergic cells in the pons remain silent during REM sleep (Chu & Bloom, 1973; Hobson et al. 1975; (for more see paper))
• The cat has 5 types of neurons. The 2 not seen in the rat are: REM-off and PGO-on (Saito et al, 1977; El Mansari et al., 1989,1990;(for more see paper))
• REM-off cells are aminergic.These were only found in the cat.
• PGO-on cells discharge in bursts just prior to and during PGO wave activity. These are seen in the cat (Koyama & Sakai, 2002)
• The latency from increased PPT activity to REM sleep is longer in the cat (20-60s*) than in the rat (5-10s). However the cat has longer REM sleep episodes (10-30min) than the rat (3-13 min) (Foote, 1973; Datta & Hobson, 2000)
• LDT cholinergic cells are just like the PPT in distribution and action.

Remaining Questions:

• What coordinates the wake-REM-on and REM-on cells so that they both start  firing 5-8 seconds before REM and stop 5-8 seconds before the end of REM?
• Are there no bursting cells inside the PPT or were they just not found?
• What in development determines a W-REM-on from a REM-on from a state independent cell?

Sleep-wake effects of meta-chlorophenyl piperazine and mianserin in the behaviorally depressed rat

In paper citation: (Mavanji, Meti, & Datta, 2002)

All rats in this paper were made depressed using neonatal clomipramine treatments. All rats were male. Controls were treated with saline, but handled in the same manner.

The new findings from this paper are:

1. REM sleep onset latency is significantly shorter in depressed rats than in controls. Rats spend ~25% less time in SWS before their first REM cycle.
2. The total number of REM sleep episodes is significantly (~2X) higher in depressed rats than in controls.
3. The total amount of REM sleep in depressed rats is significantly more than controls (>2X more REM).
4. mCPP, a serotonin agonist, decreased the total amount of REM sleep in the depressed rats by decreasing the total number of REM sleep episodes and increasing the REM sleep onset latency.
5. mianserin, a SSRI, decreased the total amount of REM sleep in the depressed rats by decreasing the total number of REM sleep episodes. 

Other important information:

• REM sleep deprivation in humans alleviates symptoms of depression (Vogel et al., 1975).
• REM sleep deprivation in rats normalizes deficits in sexual activity and aggression, which are symptoms of rat depression (Vogel et al., 1990).
• mCPP is known to increase serotonin release (Bauman et al., 1993) and reduce REM sleep in humans ( Lawlor et al., 1991).
• Clomipramine treated rats have less serotonin in their brain than control rats (Mavanji & Meti, 1999).
• Serotonin inhibits REM sleep (McCarley, 1982) and so serotonin agonists reduce REM sleep (Quattrochi et al., 1992; Stickgold et al., 1993)
• mCPP normally reduces REM in the controls if it is injected systemically because it inhibits acetylcholine release (Vizi et al., 1981) It didn't in this case because it was injected  ICV.
• Mianserin typically reduces REM in both depressive patients and normal subjects (Mendlewicz et al., 1995; Tormey et al., 1980).

Remaining questions:

• How does the clomipramine rat model work? Would this still be the case in social stress depressed rats, or learned helplessness rats?
• The CLI+mianserin group seemed to have low wakefulness and high SWS in my opinion. I'm surprised that it didn't come out significant.

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?

Targeted marketing

I love it when charity organizations are clever; it is often so difficult for them to target the group that they want to target. In this case, a skin cancer prevention group posted an advertisement for a free trial of tanning lotion that "triples the effect of the sun." The full story is here.

The Pro-Life Battle Cry: "I want to adopt your baby!"

My husband just sent me the link to this blog, which encourages Christian families to adopt special needs and abortion-bound babies.

God has really laid it on my heart that when the time comes in which we could adopt, the place to go is really outside the abortion clinic. As a moderate Malcolm Gladwell reader, I do believe that the marketing and convenience of an idea can make all the difference in whether the idea succeeds. If I were a woman who didn't feel that she had options, I would be looking for an instant out. If, instead of saying, "there is a nebulus family out there who could help you raise your family," we said, "Right now, we want to see you through your pregrancy and adopt the baby you have," it would be more concrete and more of a real option.

And let's face it, what is cooler than saving lives?

Hama Rules

Yesterday, my husband reminded me of a chapter I read in Thomas Friedman's book, From Beirut to Jerusalem, and he also sent me this NY Times article on the Hama Rules and how they have evolved to fit the current political situation.

In 1982, the majority of Syrians were Sunni Muslims, yet they were not in power. Syria was a closed country at the time, like North Korea is today, so most news came as only rumors to the rest of the world. The ruling Alawite regime was the minority group in power, and they used every means available to keep the rest of the country at bay. When the Sunnis decided to revolt in the city of Hama in February of 1982, the government shelled the city and blew up building after building, full of civilians. They killed 20,000 people. This was an act of terrorism that said, "Don't even think about trying to overthrow us. We can crush you." That May, the government opened up the city and invited Syrians from all over the country to see the carnage and get the not-so-subtle message: we will not hold back to get what we want.

Now, the Syrian government is attack its own people again and the country is in revolution. Is it that people have forgotten just how brutal their leaders are? Or is it that terrorism is not enough to prevent the human spirit from flourishing and people from seeking human rights?  Only time will tell. And we can only pray that Syria repents from using bloodshed to secure power.

The Beautiful Tree: A Personal Journey Into How the World's Poorest People Are Educating Themselves by James Tooley

The Beautiful Tree is a great book for anyone interested in effective models of education in international development. The main thesis is that there are private schools for poor children in the slums of almost every developing country that are out performing their government sponsored competitors. Throughout the book, Tooley meets with development experts and influential politicians who all share one common belief: private schools are only for the wealthy. Tooley makes a great argument for why the private schools are often better: because if parents are unhappy with their children's education, they take their kids and their money elsewhere.

Tooley also exposes the inefficiency of the IMF, and argues that government-sponsored schools are a western model that doesn't even work perfectly in the west, and that this model is imperialistic. He backs his argument with historical records of private schools that existed well before the IMF was ever created. I think that he gets a little heavy handed with his argument that western school systems are imperialistic, but he also does an excellent job testing kids in both government and private schools and he shows that the kids in private schools learn better than their peers. He also provides lengthy data that the kids in  private school are mostly gender mixed and that their parents earn paltry sums, but value education. The private schools are very cheap.. most are less than $10 for a school year in the slums of Hyderabad, India.

Conclusion:
A good read, I would recommend it!