(1) when rats are sleep-deprived, small populations of rat brain neurons can fall asleep while the rest of the rat is awake, and
(2) this may correspond to performance degradation

summary:
http://arstechnica.com/science/news/2011/04/if-you-only-feel-half-awake-you-probably-are.ars

article:

http://www.nature.com/nature/journal/v472/n7344/full/nature10009.html

i haven’t read the actual article yet…

Through its innovative structure, WNYC’s RADIO LAB (www.radiolab.org) blends storytelling, interviews with top scientists, music and innovative sound design to explore big ideas such as Morality, Space, Identity.

The hosts are Jad Abumrad, one of public radio’s youngest producers, and Robert Krulwich, veteran broadcast journalist for ABC with a sub-speciality in science. Together they create a “two guys chatting in a bar” feel, making complex scientific ideas accessible and exciting.

The series launches in NYC on WNYC on Friday, May 18, but will be available to anyone, anywhere as a podcast starting May 22. Podcasts and on-demand streaming can be found at www.radiolab.org.

An afternoon of video games with a Harvard sleep expert. A first-hand look at the psychological power of the doctor’s white coat. A lesson on the dire effects of sleep deprivation, through the eyes of a new mother.

Radio Lab, WNYC, New York Public Radio®’s highly-acclaimed show about wonder, discovery, and big ideas, is back!

Season 3 launches nationally on WNYC on Friday, May 18, and will air on over 100 public radio stations around the country throughout the spring and summer. Program descriptions below.

This season, co-hosts Jad Abumrad and Robert Krulwich tackle five new fascinating topics: Placebo, Sleep, Zoos, Memory and Forgetting and Mortality. They begin with seemingly simple questions — Could the best medicine be no medicine at all? Is there such a thing as a good cage? Is love a more powerful force than memory? – that serve as a launch pad into the unknown. Embarking on a curiosity spree, they unearth the implications of the latest scientific findings, stumble into surprising stories, and traverse philosophy, history, and culture, checking in all along the way with the scientists doing the real work.

SCHEDULE: RADIO LAB – Season 3
May 18 – June 15
Special 5-Week Season of Radio Lab
Fridays: 2pm on WNYC AM 820 / 3pm on 93.9 FM
Sundays: 6pm on 93.9 FM
Via live webstream and on-demand at www.wnyc.org

June 11 – 15
Encore of all five episodes
Daily: 2pm on WNYC AM 820 / 3pm on 93.9 FM
Via live webstream and on-demand at www.wnyc.org

PROGAM DESCRIPTIONS – in order of broadcast

Placebo
Could the best medicine be no medicine at all? The hour begins with a skeptical Kwakiutl Indian trained in shamanistic healing. He knows that his ritual healing is just a trick and yet he wonders: why does it work? With new research demonstrating the startling power of the placebo effect, Radio Lab examines the chemical consequences of belief and imagination. Jad Abumrad tours a hospital with his father, Dr. Abumrad, and witnesses the power of the white coat. After visiting 18th century France to witness the first double-blind placebo test, the show ends with reporter Gregory Warner’s visit to a Christian faith healer in a lakeside tent revival in New York’s Adirondack Mountains.

Sleep
Every creature does it – from giant hump back whales all the way down to fruit flies – and yet science still can’t answer the basic questions: Why do sleep? What is it for? In Radio Lab’s search for the answer we visit Harvard sleep researcher Dr. Robert Stickgold to play video games before dropping in on MIT’s Dr. Matt Wilson as he peers into the brains of slumbering rats. We hear from a mother who is sleep deprived and learn from UPENN’s Dr. Alan Pack about the toxicity of sleep deprivation. Our last stop in the hour is with Dr. Guilio Tononi for a theory on what slow wave sleep might be doing for our brains that is so important, we literally cannot live without it.

Zoos
In a cruel trick of evolution, humans can stand just three feet from a ferocious wild animal and still be perfectly safe. Is there such thing as a good cage? Neuroscientists are looking into the brains of caged animals to see the effects. But how far are we willing to go to do what is best for the animals in our care? NPR science desk reporter Nell Boyce takes us to Toledo, OH for a carcass feeding and reporter Jocelyn Ford goes one step further to a live animal feeding at a rural zoo in China. We end the hour with the story of one man’s promise to a big cat at the Bronx zoo — which took him to all they way to Belize to fulfill — to create the world’s first jaguar preserve.

Memory and Forgetting
According to the latest research, recall is an unstable and profoundly unreliable process. It’s easy come, easy go as we learn how true memories can be obliterated and false ones added. And Oliver Sacks joins us to tell the story of an amnesiac whose love for his wife and music transcend his 7-second memory.

Mortality
Is death a fact of life or a disease that can be cured (as some scientists claim)? When Dr. Leonard Hayflick discovered in 1962 a phenomena known as the ‘Hayflick Limit’ — that cells have a natural limit to their reproduction — the study of longevity was born. We hear from Dr. Cynthia Kenyon, whose tinkering with worm DNA brings her face-to-face with a grim reaper gene. We filter the modern search for the fountain of youth through personal stories of witnessing death…the death of a cell, the death of a loved one…and the aging of a society.

WNYC, New York Public Radio, is New York’s premier public radio station, comprising WNYC 93.9 FM and WNYC AM 820. As America’s most listened-to public radio stations, reaching more than one million listeners every week, WNYC FM and AM extend New York City’s cultural riches to the entire country and air the best national offerings from affiliate networks National Public Radio, Public Radio International and American Public Media. WNYC 93.9 FM broadcasts a wide range of daily news, talk, cultural and classical music programming, while WNYC AM 820 maintains a stronger focus on breaking news and international news reporting. For more information, visit www.wnyc.org.

# # #

Yet the device itself is expensive and rare — they can run from $20,000 to $50,000 or even more, despite the fact that they are, in essence, a coil, a switch, a bank of capacitors, and a power supply. Much of the art lies in making the devices safe and fail-proof. Is it possible to hack/engineer a system that is safe, fault-tolerant, efficacious, and inexpensive? And furthermore, can we facilitate a community that will devise such devices, and share information about protocols and approaches to brain hacking?

This past August at Foo Camp, a hackers’ conference in Northern California, a group of people got together and set out to do just that. We are designing a safe, noninvasive, modular, and “open source” brain stimulator that will open up the field of circuit modulation to a wider audience. Members of the group include therapists and mental health professionals, engineers, programmers, and others interested in either the development of such devices, or the sharing of information on this front. Key to the design is safety — we want to make sure that the devices we create are as safe as devices on the market. Also, all the information is released under the Creative Commons “Attribution and Sharealike” license. This is a new model for “open source” medical device development — which may move it beyond the domain of simply creating “cool toys,” and to creating real devices.

You can find out more information, or contribute to the project, or learn from the project, at
http://transcenmentalism.org/OpenStim/

-Ed

Introducing CX717, a drug being developed by Cortex Pharmaceuticals of Irvine, California. It’s the first of what promises to be many aimed at detaching people from the daily routine of eight hours each for work, rest and play.

Tests conducted on rhesus monkeys last year suggest that CX717 can wire users to remain awake for 36 hours without the jitters, euphoria and eventual crash that come after mega-doses of caffeine or amphetamines. Further down the line are even more radical compounds—stimulants that can wipe out sleep for several days at a stretch, and pills that deliver a whole night’s shut-eye in two hours.

More information about the ampakine CX717 can be found here. We previously mentioned the delay match-to-sample performance improvement of monkeys on CX717.

I don’t know quite what to make of this. In fact, I just don’t understand what is going on. But I can definitely think of examples from my own life where this is true. Sometimes not thinking about a problem really does lead to its solution and it’s fascinating to think about why this may be.

Also, the authors draw a connection between what they call unconscious thought (as performed in their experiments) and insights that can come “after sleeping on it”; I’m not sure these phenomena are the same. I think sleep taps into deeper organization processes that are not available on the timescale of unconscious thought, as given in the experiment.

Abstract:

Contrary to conventional wisdom, it is not always advantageous to engage in thorough conscious deliberation before choosing. On the basis of recent insights into the characteristics of conscious and unconscious thought, we tested the hypothesis that simple choices (such as between different towels or different sets of oven mitts) indeed produce better results after conscious thought, but that choices in complex matters (such as between different houses or different cars) should be left to unconscious thought. Named the “deliberation-without-attention” hypothesis, it was confirmed in four studies on consumer choice, both in the laboratory as well as among actual shoppers, that purchases of complex products were viewed more favorably when decisions had been made in the absence of attentive deliberation.

Some interesting facts from the NYT article:

• Sleep patterns vary greatly. Some bats sleep 20 hours, giraffes get 2 hours. (hmmm… grad students might be evolving toward giraffes…)
• Sleep has recently been found to occur in invertebrates too. Alternatively stated: Sleep is evolutionarily very old.
• Slow wave sleep is also found in fruit flies. (Divergence from fruit flies for us was 600 million years ago.)
• Some people don’t have any REM sleep. Behaviorally, these people are entirely normal, implying that it’s purpose might not be as obvious as one had thought (ie. required for the preservation of new memories, etc.)
• If you put a bunch of ducks in a row, the ones on the inside will sleep more often with both eyes closed. The ones on the outside will sleep with one eye open and it is (always?) the eye facing outward from the huddle. They are able to “sleep” one half of the brain at a time and, apparently, this sleeping with one eye open was lost in higher mammalian evolution. Fascinating.

Apparently, CX717, an ampakine developed by Cortex Pharmaceuticals, shows some signs of preventing the cognitive impairment brought on by sleep deprivation. The original study in PLoS Biology (news & views) was done with monkeys.

Bridging the gap: coupling single-cell oscillators in the suprachiasmatic nucleus
Christopher S Colwell

Christopher S. Colwell is in the Department of Psychiatry and Biobehavioral Sciences at the University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, California 90024, USA. ccolwell@mednet.ucla.edu

Neurons in the mammalian master clock can maintain circadian rhythms in isolation, but must synchronize to function as a time-keeping system. A new study finds that gap junctions between neurons promote synchronous electrical activity and rhythmic behavior.
From daily sleep cycles to dinnertime, the circadian system is responsible for the timing of behavior and physiology. In mammals, the conductor of this multifaceted timing system can be localized to a pair of structures in the hypothalamus known as the suprachiasmatic nucleus (SCN)1. Individual SCN neurons in isolation have the capacity to generate circadian oscillations in electrical activity, secretion and gene expression, but the cells drift out of phase with each other2. Understanding how individual oscillators remain synchronized in the intact SCN has been a fundamental gap in our knowledge of SCN function. In this issue, Long et al.3 unambiguously demonstrate that SCN neurons are electrically coupled and that this coupling not only promotes synchronization of neural activity, but also is required for the maintenance of circadian rhythms in behavior.

The authors made intracellular recordings from pairs of neighboring SCN neurons. They found that about 25% of the neurons were electrically coupled and that these coupled cells showed synchronized spiking activity. The coupling strength and biophysical properties were similar to those measured in other types of coupled neurons4. Gap-junction channels are formed by a family of proteins called connexins. Connexin 36 (Cx36) is a major component of gap-junction-mediated electrical coupling in neurons4, and this seems to be the case in the SCN. Long et al. found that the electrical coupling between SCN neurons was lost in Cx36 knockout mice3. As compared to regions like the inferior olive, the new study found that the percentage of coupled cells in the SCN was relatively low3. This lower coupling frequency between SCN neurons seems to be consistent with our knowledge of SCN physiology. These clock cells do not show absolutely synchronized action potential generation; instead the population has coordinated firing rates that are high during the day and low during the night. However, it may be that some cell populations within the SCN are highly coupled and others not at all.

To determine whether gap-junction-mediated electrical coupling may also be involved in behavioral rhythmicity, the authors turned to the best-characterized behavioral output of the circadian system?namely, the wonderfully precise rhythms in wheel-running activity. In a light:dark cycle, both wild-type and Cx36 knockout mice synchronized to the lighting conditions and showed nocturnal activity rhythms characteristic of rodents. However, in a light:dark cycle, photic input organizes the temporal pattern of activity by synchronizing an endogenous clock to the period of the environmental signal (entrainment) as well as directly regulating activity (masking). To distinguish between these two effects of light, the authors placed the mice in constant darkness and measured their activity rhythms without light cues. In these conditions, the Cx36-deficient mice showed rhythms that were weaker and less coherent than those of controls. These deficits seemed to be due to a greater tendency for the KO mice to be active at inappropriate times in their daily cycle. The cycle-to-cycle variability in the onset of the daily activity bout was also higher in the mutant mice. Thus, without Cx36, the circadian clock still keeps time but lacks the temporal precision that typically characterizes the behavioral output.

The Long et al.3 study helps to resolve a controversy about the presence and role of gap junctions in the SCN. The first suggestion that nonsynaptic mechanisms may link SCN neurons came from the observations that circadian rhythms in glucose utilization are present in the SCN before synapse formation5. In addition, when synaptic transmission is blocked by the removal of extracellular calcium, SCN neurons are still weakly coupled such that the activity of one cell increases the probability that a neighbor will generate an action potential6. A tracer (biocytin, neurobiotin or Lucifer yellow) placed in one SCN neuron spreads to clusters of surrounding cells7, 8, 9. Dye coupling definitively marks the presence of gap junctions. However, because the dye-coupled cells in these studies were not physiologically characterized, it was unclear whether they were neurons, astrocytes or other non-neuronal cell types. Pharmacological gap junction blockers, such as halothane, disrupt circadian rhythms in SCN electrical activity and peptide secretion, as well as light-induced phase shifts of the circadian rhythm in wheel-running activity10. Unfortunately, these pharmacological tools are not very selective, and these agents have other effects besides blocking gap junctions. Anatomical studies have shown clear evidence for coupling between astrocytes and oligodendrocytes in the SCN11, but proof of neuron-to-neuron coupling has proven elusive until recently. First, results from freeze-fracture and immunocytochemistry provided evidence for Cx36-containing gap junctions between SCN neurons (Rash, J.E., et al., 749.11, Soc. Neurosci. Abstr., 2002). Now the new study3 demonstrates that SCN neurons are indeed electrically coupled and that this coupling is important for circadian rhythms in behavior (Fig. 1).

Like many good studies, this work raises as many questions as are answered by the experimental data. For example, we need to consider what signals are being spread from cell to cell via the gap junctions. Unlike chemical synapses, communication via gap junctions is bi-directional and allows passage of small molecules (up to 1 kDa), thus linking cells both electrically and metabolically. Signaling molecules such as cyclic AMP, cyclic GMP, IP3 and calcium may be able to pass between neurons through these connections. Future studies will have to consider the possibility that the passage of small molecules between cells may be as important as the direct passage of current. Gap-junction coupling also acts like an electrical filter in that some signals will pass more readily than others. During the day, SCN neurons undergo oscillations in membrane potential (2−8 Hz) that are driven by voltage-gated calcium currents, among other ionic mechanisms12. These slower changes in membrane potential should pass more effectively through gap junctions than the fast voltage changes that occur during an action potential.

One of the more tantalizing observations in the new study was the suggestion that the electrical coupling between SCN neurons may itself be subject to diurnal variation. The authors found that coupling was greater in the middle of the day, when rhythmic neural activity in the SCN peaks, than in the late day or early night. This observation is consistent with previous work demonstrating circadian variation in dye-coupling between SCN neurons8. In a few previous cases, changes in gap-junction permeability could be linked to changes in physiological function. For example, in the supraoptic nucleus of the hypothalamus, increased electrical coupling of oxytocin-secreting neurons may be a critical component of the milk-ejection reflex13. These types of observations raise the possibility that gap junctions do not just allow the passive spread of current, but instead form an actively regulated communication system whose properties vary with the state of the organism.

Another unresolved issue concerns the relative roles of electrical and chemical synaptic transmission in coupling SCN neurons. It is widely accepted that most SCN neurons express GABA and are likely to use this neurotransmitter for synaptic communication with other neurons in the SCN. In culture, GABA, acting through the GABAA receptor, can synchronize the electrical activity of SCN neurons9, 14. Thus the synaptic release of GABA may act in concert with gap junctions to synchronize the neural activity of individual SCN oscillators. The SCN is made up of several cell populations whose specific functions we are just beginning to understand. One appealing hypothesis is that gap junctions may be more important for linking cells within a cell population, and that synaptic mechanisms may be more important for communication between SCN cell populations. Of course, it is also possible that SCN neurons are coupled by multiple, overlapping mechanisms, which may not be independent. Two studies looking at dye coupling within the SCN found that activation of GABAA receptors by muscimol actively inhibits the coupling8, 15. Sorting out the relative role of these interacting coupling mechanisms should keep SCN watchers busy for years to come. These mice and this new research3 should help us bridge the gap between cellular coupling and circadian behavior.

Newer review article: Joan C. Hendricks. Genetic Models in Applied Physiology: Invited Review: Sleeping flies don’t lie: the use of Drosophila melanogaster to study sleep and circadian rhythms. J Appl Physiol 94: 1660-1672, 2003. 10.1152/japplphysiol.00904.2002

Summary article

Actual article (Nature AOP)