1 of 8 6/20/2012 10:25 AM Sleep and Dreams Sleep and the Brain pdf NIH Overview 3.2-3.3 Some Basic Background: Back to Course Schedule (The material below on the neuron is adapted from: http://vv.carleton.ca/~neil/neural/neuron-a.html) The Neuron. The brain is a collection of about 10 billion interconnected neurons. Each neuron is a cell [below] that uses biochemical reactions to receive, process and transmit information. A neuron's dendritic tree is connected to a large number of neighbouring neurons. When one of those neurons fire, an excitatory or inhibitory signal is received on either a dendrite or the soma (cell body). All of the incoming excitatory and inhibitory signlals are added together through the processes of spatial and temporal summation. Spatial summation occurs when several weak signals from different locations are converted into a single larger one, while temporal summation converts a rapid series of weak pulses from a single source into one large signal [Note from Ferguson: summation interval ~ 5-100 msec.) The aggregate input is then passed to the axon hillock. If the aggregate input is greater than the axon hillock's threshold value, then the neuron fires, and an output signal(action potential) is transmitted down the axon. The strength of the output is constant, regardless of whether the input was just above the threshold, or a hundred times as great. The output strength is unaffected by the many divisions in the axon; it reaches each terminal button with the same intensity it had at the axon hillock.
2 of 8 6/20/2012 10:25 AM Each terminal button is connected to other neurons across a small gap called a synapse [left]. When an action potential arrives at an axon's terminal button, a neurotransmitter is released which then attaches to a receptor site on the surface of the post-synaptic neuron. This in turn triggers a response in the second cell. Some neurotransmitters are excitatory, which simply means they make the post-synaptic neuron more likely to fire. Other neurotransmitters are inhibitory, making the post-synaptic cell less likely to fire. The net result of all the excitatory and inhibitory signals arriving at a neuron at any one time determines whether or not the cell fires. After being released into the synaptic space, molecules of the neurotransmitter are quickly either reabsorbed into the terminal button (reuptake) or neutralized by enzymes. Many of the most powerful drugs (alcohol, LSD) and medications (Prozac, Valium, Ambien) work by altering the effect of neurotransmitters.three main methods of drug action are to : inhibit reuptake, effectively increasing the amount of neurotransmitter in the synapse block the receptor sites, thus reducing the effect of the neurotransmitter mimic a neurotransmitter Some brain bits relevant to sleep: A Brief History of Research on the Biology of Sleep
3 of 8 6/20/2012 10:25 AM 1. Constantin von Economo (WWI) Damage to anterior hypothalamus & basal forebrain = great difficulty going to sleep Damage to posterior hypothalamus & midbrain = continuous sleep Conclusion: sleep & wake are controlled by different parts of the brain 2. Frederic Bremer (1930s) Bremer's interpretation: sleep is the brain's natural state and sensory input (which is greater in Encephale isole) is needed to 'push' the brain into wakefulness. 3. Giuseppe Moruzzi & Horace Magoun (1940s) 4. Wakefulness is triggered by activity in the reticular activating system (RAS), which lies between Bremer's 2 cuts. A contemporary view: activity in the RAS, which can be triggered by incoming sensory stimuli, results in widespread activation of the cerebral cortex. Damage to the RAS leads to a low level of alterness and large, slow, synchronized EEG waves characteristic of sleep.
4 of 8 6/20/2012 10:25 AM The Major Sleep/Wake Sites and Pathways The information in this section has been abstracted from several sources, including: Biopsychology, 8th Ed, by John Pinel; Biological Psychology by S.B. Klein and B.M. Thorne, and Biological Psychology, 10th Ed., by James W. Kalat, along with several recent journal articles and other publications. However, our understanding of the CNS mechanisms responsible for Wake, NREM and REM has been growing so quickly that by the time you read this, some of the material in the following section may be out of date, but every effort has been made to make it accurate as of summer 2011. Let's start with some of the brain sites that are major players is the sleep/wake process: Overall Regulation of the Circadian & Homeostatic Sleep-Wake Cycles Here's an overview of the regulatory systems described above, not all of which are able to be shown in the figures below. Wake RAS Arousal (wake) Pathway:
5 of 8 6/20/2012 10:25 AM (Histamine) (ACh & NE) (ACh) SCN ---------------->RAS ------------------> Thalamus ----------------->Cortex Note: the RAS can also be activated by incoming stimuli...particularly stimuli that are intense, unexpected or interesting. Lateral Hypothalamus (wake maintenance) Pathway (excitatory) (orexin) (ACh) SCN--------------->LH------------>Basal Forbrain------------>Cortex Note 1: Orexin deficiency produces narcolepsy. Note 2: Orexin also plays an important role in feeding behavior and energy homeostasis. Might this be relevant to Rechtschaffen's rat studies? NREM Sleep Circadian VLPO (NREM Sleep) Pathways: (Inhibits) (GABA) SCN---------------->VLPO------------>BF+, RAS, Cortex Homeostatic Basal Forebrain and VLPO Pathways (Activates) (GABA) Adenosine---------------->VLPO ------------>BF+, RAS, Cortex (Activates) (GABA) Adenosine---------------->BF- -------------->Cortex (Inhibits) (ACh) Adenosine---------------->BF+ -------------->Cortex??????? Note: the SCN pathway above is circadian, while the Adenosine pathways are homeostatic Serotonin: Serotonin in a neurotransmitter that appears to activate the inhibitory regions of the basal forebrain and thus help induce sleep.
6 of 8 6/20/2012 10:25 AM The shift from waking to NREM sleep: Some additional factors Core temperature and peripheral blood flow. One important factor in inducing sleep is to reduce the temperature of the brain and the body's core. Lying down helps to shift blood flow to the peripheral parts of the body (hands & feet), so if the room is cool, this shift of blood to the extremities cools the blood & eventually the brain. External stimulation. External stimulation, especially if it is intense, unpredictable or meaningful, activates one of the excitatory regions of the reticular system. Eliminating such stimuli reduces activation of the RAS. Prostaglandins. This is a group of sleep-inducing proteins which are found throughout the body and which build up during activity. Prostaglandins are also are released when the immune system responds to infection Here's a site from Zach that may offer opportunities to help people who have trouble making the transition from wake to sleep The Transition from NREM to REM Sleep (pp. 90-95) Remember the glucose uptake data shown in the image above? If the SCN were the only factor influencing the sleep-wake cycle, then sleep patterns would simply follow the pattern of SCN activity: with the approach of evening, arousal would slowly decline until we fell asleep. Sleep would then gradually get deeper and deeper until a low point around 2:00-3:00 AM, at which time the cycle would reverse and arousal would gradually increase, eventually waking us up. Arousal and alertness would then continue to increase till the high point is reached around 2:00PM, and the 24-hr cycle would start all over again. To some extent, this is what we see...sws generally is most pronounced during the first half of the night (i.e. till about 2:00 or 3:00 AM if you go to bed at 11:00 PM) and then is increasingly replaced by REM (a more activated brain state) as morning approaches. Clearly, however, there is more to the sleep cycle than this simple 24-hr ebb and flow. In particular, we experience significant variations in CNS arousal on a 90 minute cycle all night long. This cycling between NREM to REM sleep involves several CNS mechanisms. Here are some relevant observations: 1. 2. 3. As early as 1949, Moruzzi and Magoun found that stimulation of locations in the reticular sytem in the brain stem led to activation of the cerebral cortex and arousal. Sometimes, depending on the location stimulated, the activation of the cortex was accompanied by increases in muscle tone and the excitability of spinal reflexes (wake?). Other locations produced cortical activation accompanied by reduced muscle tone and inhibition of spinal reflexes (REM?). When the Pons is surgically isolated from the cortex, then REM disappears and EEG recordings from the cortex show cycling only between wake and NREM! On the other hand, when the Pons is surgically isolated from the spinal cord, then the cortex shows relatively normal Wake-NREM-REM cycling. The Pons contains 2 groups of cells, called "REM-Off" and "REM-On" cells, which alternate about every 90 minutes. When one of these sets of cells become active, they inhibit the other set of cells and, at the same time, gradually turn themselves off, thus allowing the other set to become active again. Then, when the second set become active, they turn themselves off and while re-activating the first set. This odd interaction leads to an alternating pattern of activity in the two sets of cells.
7 of 8 6/20/2012 10:25 AM Figure adapted from The Brain and the Inner World, M. Solms and O. Turnbull, 2002 At the risk of adding one final layer of complexity, it turns out that there are actually two different aspects of REM: tonic and phasic. The tonic aspects persist througout each REM period, while the phasic aspects are intermittent. Here's more: Tonic: Phasic Selected areas of the cortex show arousal at levels equal to waking, hence the very active EEG seen in REM The locus coeruleus region of the pons (see image above) blocks motor commands as they pass down through the brainstem on their way to the muscles, hence REM paralysis. Damage to the locus coeruleus eliminates REM paralysis and produces an odd phenomenon called REM movement disorder. occasional rapid eye movements heart rate increases blood pressure increases respiration increases cerebral blood flow increases Penile and clittoral tumescence occur...unrelated to dream content The following locations are relatively inactive or blocked: dorsolateral prefrontal cortex (working memory and the organization of behavior sequences) sensory input Sudden, periodic bursts of activity (called PGO spikes) are seen in some of the REM-On cells in the Pons. These bursts then spread to the visual parts of the brain and to the muscles that move the eyes. During phasic REM, the following locations are especially active: LGN and occipital cortex (vision)
8 of 8 6/20/2012 10:25 AM vestibular nucleus (balance, orientation and movement) primary motor cortex (muscle movements) limbic system (emotions and memory) occipital/parietal junction (language and vision) the arousal threshold increases rapid eye movements increase and occur in clusters heart rate inreases even more and becomes variable blood pressure increases even more and becomes variable Finally, it should be noted that Nathaniel Kleitman (the father of sleep research) proposed that this 90 min. cycling is not unique to sleep; rather, Kleitman argued that it continues throughout the day; its effects are just less noticable in the midst of all of our daytime activity. He called this the Basic Rest-Activity Cycle (BRAC). The existance and/or relevance of such an ultradian cycle is a bit controversial. You can take a look a some recent evidence: click here.