Psy 319 Exam 4 - Dr. Sabol

Control of Circadian Rhythms in Sleep and Waking by the SCN (figure 9.28) - SCN activating SPZ

Figure 9.28 describes the activity of the pathway during the light portion of the 24 hours cycle: - Once info arrives at the SCN, it communicates with a nearby region called the sub-paraventricular zone (SPZ) - The SPZ then, activates the dorsal medial hypothalamus (DMH). - The dorsal medial hypothalamus then does two things. The first is it inhibits the slow-wave sleep on region, the vlPOA. - At the same time, it activates the orexin neurons of the dorsal lateral hypothalamus (DLH), so you can see the black line is an activation. - And we already know that activation of the orexin neurons will also activate the rest of the arousal system, acetylcholine, norepinephrine, serotonin and histamine. - There's redundancy built into the system, so the suprachiasmatic nucleus (SCN), has two ways of communicating with the SPZ. - The first way is through traditional neural communication that we described in the previous slide. - But SCN also secretes a protein called prokineticin 2 (PK2) - Prokineticin 2 (PK2) diffuses throughout the ventricular system of the brain, and then it activates receptors in the SPZ through this route. - So there are two, as we said, two ways for the SCN to activate the SPZ. *** During the day cycle, the DMH inhibits the vlPOA and excites the orexinergic neurons of the LH. Orexin then activates the arousal systems, thus stimulating wakefullness.***

Hunger signals vs. Satiety signals

Hunger Signals: - stimulate activity, motivation, and eating - inhibit metabolism to conserve stores Satiety signals - inhibit eating -remove inhibition of metabolism

REM: dreams

Hypnagogic hallucination refers to the vivid dreams that may occur during sleep paralysis.

Genetic Mutations contributing to Obesity

MC4 receptor gene - two important neuropeptides bind to MC4 (Alpha-MSH which inhibits eating and AGRP which activates eating). FTO gene (carries genetic info to produce enzyme that influences metabolism) Leptin gene (very importnat satiety signal, so if the individual is mutated and doesn't produce as much leptin then there will be a decreased satiety signal and the person will likely overeat)

Free radicals

Naturally occurring, highly reactive chemicals that form in the presence of oxygen. Unstable molecules that cause biochemical aging, especially wrinkling and sagging of the skin.

Prefrontal Cortex

Research with transcranial direct current stimulation suggests that the prefrontal cortex is involved in lucid dreaming.

VTA Dopamine and Endocannabinoids (both neurochemicals)

VTA Dopamine - dopamine neurons are located in the cetral tegmental area (VTA). - contain ghrelin receptors - researchers found that if they injected ghrelin into the VTA, it induced eating. Endocannabinoids - Increase release of MCH and orexin which increases eating as well.

Electroencephalogram (EEG)

An amplified recording of the waves of electrical activity that sweep across the brain's surface. These waves are measured by electrodes placed on the scalp. - basically just know that it records the brains activity - The beta pattern of EEG activity is characterized by irregular, high-frequency (13-30 Hz), low-voltage waves.

Health risks associated with obesity

- diabetes - cardiovascular disease - stroke - arthritis - cancer

Gastric Factors (empty stomach)

(fasting phase) Release of Ghrelin (hormone) by stomach - travels to brain via bloodstream Grehlin detectors: - in hypothalamus - initiate eating

Adenosine - Neural Control of Sleep

- Adenosine is important in regulating the onset of sleep. - Sleep Debt (the body makes up for lost SWS and REM) - What regulates this? Adenosine. - When the brain is active, astrocytes play a very important role in delivering energy to our neurons. They use stored glycogen to deliver this energy to neurons. They also release adenosine. - Adenosine accumulates during wakefullness and is reduced during slow-wave sleep. During SWS (resting brain): - the glycogen in astrocytes is restored Role of Caffeine: - Block adenosine receptors (binding site) on neurons. (They can't both attach the the receptor at the same time so one blocks the other). - Adenosine receptors are blocked by caffeine, which in turn promotes wakefulness. - Decrease adenosine's "sleep signal"

Homeostatic factors

- After period of sleeplessness: increased sleep Mechanism: - Adenosine (induces drowsiness): accumulates during waking and decreases during SWS. - Ex: Cat is sleepy (high Adenosine). Cat takes nap (Adenosine lowering). Cat is no longer sleepy.

Ryback and Lewis (1971)

- Asked whether there is a need for sleep to recover from the days activities. -Found no decreases in slow-wave sleep or REM sleep of healthy subjects who spent six weeks resting in bed - Conclusion: Sleep is not needed to provide rest after phsyical activity.

Acetylcholine: Function - Arousal, alterness

- Brain region containing cell bodies: Pons, Basal Forebrain, Medial Septum. - Neurotransmitter that plays an important role in the neural control of arousal as well as an important role in Waking and REM sleep (EEG is desynchronized during Waking and REM so the brain is active). - So ACh release is high during waking, drops during SWS, and then is high again during REM sleep. Pons and Basal Forebrain ACh activated: - increased ACh release in cortex - desynchronized cortical EEG Medial Septum activated: - Increased ACh release in

Circadian rhythms (1st biological clock)

- Controlled by both the external light cycle and internal clock of the organism. - Light controls the interal clock (called the Zeitgeber), keeping it at 24 hrs. (in other words, the onset of morning light resets the internal clock to make sure that the internal clock will run at 24 hours).

Histamine: Novel Stimuli

- Histamine nuerons are located in the tuberomammillary nucleus (TMN) of the hypothalamus. - Activates cortex both directly (direct projections) and indirectly by activating the ACh neurons of the basal forebrain and the pons. - During the Waking state, the activity level of histamine neurons is very high. - During SWS and REM sleep, the activity levels are low. - The function of Histamine was investigated by Takahashi et al. (2206), and they concluded that it was important in increased arousal, but in a very particular set of circumstances. It was important in increased arousal specifically in the presence of Novel Stimuli. In other words, a very high level of vigilance rather than simply mediating wakefullness.

Sleep deprivation: healthy volunteers

- Horne (1978): researchers asked is sleep necessary for demanding physical exercise. The answer appears to be no. - physical exercise is NOT impaired. - Cognitive function IS impaired. (Difficulty concentrating. Perceptual distortions).

Ghrelin

- If ghrelin levels remain high continuously, an individual would likely experience continuous eating behavior. - Ghrelin acts on NPY neurons to stimulate feeding. - One explanation for why it is hard to maintain a low-calorie diet is that food restriction elevates ghrelin release, which triggers hunger. - The Roux-en-Y gastric bypass procedure produces weight loss by decreasing plasma ghrelin levels. - The entry of ingested food into the duodenum can suppress further eating via the suppression of ghrelin secretion from the stomach.

Orexin: Exploratory behavior

- It's cell bodies are located in the lateral hypothalamus (LH). Orexin Neurons: - have high levels of activity in the Waking state. - low levels of activity during the SWS and REM.

Neurochemicals that stimulate eating/hunger

- Melanin-Concentrating Hormone (MCH) - Orexin - Neuropeptide Y (NPY) - Agouti-Related Protein (AGRP)

Consolidation of Non-declarative Memory

- Non-declarative memories are memories for tasks and activities that are demonstrated through action. Things like driving a car or riding a bike. So we demonstrate that we've learned to ride a bike by actually riding the bike. - Recent research suggests that REM sleep is important for nondeclarative memory.

Norepinephrine: Function - Vigilance

- Norepineprhine cell bodies located in the Locus Coeruleus (LC). - In the waking state, the neurons are most active, and norepinephrine is released throughout the brain (which is thought to be very important in vigilance - the ability to maintain one's attention to the different stimuli in our environment). - During SWS, these neurons are less active. - During REM sleep, they show no activity at all. - The increased arousal and sleeplessness produced by amphetamine is related to the release of norepinephrine

Serotonin ( also called 5-HT) : Automatic ongoing movements

- Serotonin's cell bodies are located in the Dorsal Raphne Neurons. - During the waking state, their very active. - During SWS, they diminish their activity. - During REM sleep, they're very inactive (close to zero). *** Notice their pattern of activity above is very similar to that of norepinephrine neurons. However, their function is quite different. - During the waking state serotonin is very important in mediating automatic ongoing movements, such as walking about, locomotion. - When the animal attends to a stimulus in the environment, these neurons become less active, and it's thought that serotonin neurons may actively suppress responding to sensory stimuli that would stop ongoing movements. - Note, however, that there is a brief burst of increase in activity as the animal leaves REM sleep. - Most of the serotonin neurons in the brain are located within the raphe nuclei. - Symptoms of narcolepsy involving REM sleep (such as cataplexy) are effectively treated by drugs that facilitate both serotonin and catecholamine activity.

Narcolepsy

- Sleep attack: strong urge to sleep - Cataplexy: muscle weakness or paralysis during waking state. Remains conscious. - Sleep Paralysis: paralysis that occurs immediately before or after sleep. Symptoms: - sleep attacks (can last two to five minutes) - Cataplexy (can last several minutes. Can be caused by strong emotion or physical effort). - Sleep paralysis (occurs just before sleep onset or just after waking. Dreamlike experience called hypnagogic hallucinations) Cause: - loss of function of the orexin system (3 possible mutations that can cause this) - hereditary Treatment: - Methylphenidate (Ritalin) for sleep attacks (also used for ADD). - antidepressants for cataplexy and sleep paralysis (in other words symptoms related to REM sleep. Serotonin and NE are important in activating the REM OFF region. By enhancing them, the REM related symptoms are less likely to occur) - Modafinil (mechanism unknown, but it has been successful in treating some symptoms.)

Stages of Sleep

- Sleep stages 1-3 are termed Non-REM (NREM) sleep, whereas stages 3 is referred to as slow-wave sleep (SWS) . - The various stages of sleep are easily distinguished by changes in the electrical activity of the brain. - Waking: Alpha waves (8-12 Hz) and beta waves (13-30 Hz). - Stage 1 (NREM): theta waves (3.5-7.5 Hz). Increased synchrony of cortical neurons (more neurons active at the same time). Hypnic jerks. This period last about 10 minutes. - Stage 2 (NREM): characterized by irregular activity. Sleep spindles (brief bursts, 12-14 Hertz). K complexes (Precursor to Stage 3 - Delta). - Stage 3: slow wave sleep. Delta wave (<3.5 Hz). Deepest level of sleep. Synchronous neuronal activity meaning many neurons are active at the same time. - REM sleep: EEG is very desynchronized (brain is very active). Beta waves occur along with occasional theta waves (6-10 Hz). Rapid Eye Movements are an important characteristic of REM sleep, giving it its name. During REM sleep, individual is unable to move. Except for the nerves that control our breathing and our eye movements, the nerves controlling our movements are prevented from firing. - During an eight hour sleep period, we go through a number of different cycles and each sleep cycle lasts about 90 minutes. - Each REM episode lasts between 20 to 30 minutes, so there are going to be 4-5 REM periods during a single night.

Metabolic activity

- The metabolism of glycogen within astrocytes produces adenosine, which in turn promotes slow-wave sleep. - Working on a task that demands high levels of mental activity during the day will increase glucose metabolism in the frontal lobes.

Brain Development - 1 function of REM sleep

- The notion that REM sleep functions to promote brain development is supported by the finding that infants with well-developed brains spend proportionally less time in REM sleep than infants with poorly developed brains.

Insomnia

- There are several types of insomnia. Primary: difficulty falling asleep Secondary: difficulty falling asleep due to another condition such as experiencing pain, or psych conditions such as anxiety, meds, or cafffeine. Diagnosis: diagnosis is quite often based on self-reports which is problematic because they are unreliable. Treatments: Nonpharmacological: - CBT - Relaxation techniques -sleep hygiene Pharmacological: - hypnotics (e.g. ambien and sonata) - benzodiazepines (enhance GABA) - histamine antagonists - Insomnia can be caused by sleep apnea. - Damage to the ventrolateral preoptic area (vlPOA) would be expected to produce insomnia. - Which of the following is seen more often in adults than children? insomnia - About 9 percent of the population experiences insomnia as a persistent problem, while 25 percent experiences this on occasion.

Youngstedt (2003)

- asked what the effect of exercise on sleep would be. - Does exercise improve sleep? Their findings were ambiguous. There may be a relationship but it is quite small.

Horne and Minard (1985)

- asked what would be the effect on slow-wave sleep after a day in which individuals engaged in a very high level of cognitive activity but very low level of physical activity - brought participants to the museum, zoo, to watch a movie, etc. then went back to the lab and recorded their sleep. - Waking: Large amount of cognitive activity, minimal physical activity. - Sleep: duration normal; SWS increased. - Conclusion: SWS provides rest after high cognitive activity during waking hours.

Slow-wave sleep (SWS)

- brain activity during slow-wave sleep is associated with thoughts or images, but these are not the narrative sequences that are usually associated with dreaming. - Reports: thoughts, images, emotions (non-narrative). - So if a person is awakened during slow-wave sleep, they do not report dreams. If questioned further, they may report a specific thought, or an image, or an emotion.

Roffwarg et al. (1962)

- conducted a study to try to understand rapid eye movements. - They brought participants into the labaratory and during their periods of REM sleep, they awaken them and ask them to describe the imagery that they were experiencing in their dream. They found that eye movements were very similar to walking eye movements (same type of scene) .

Consolidation of Declarative Memory - (2nd function of SWS!)

- declarative memory refers to recalling episodes of our lives. So for example, remembering what we did last summer on vacation or what we had for dinner last night. We can recall them, think about them, and we can talk about them. - Consolidation of a memory means converting a short term memory into long term memory so that we can, in fact, recall that memory. - Tucker et al. (2006) studied the role of slow wave sleep in both a declarative and non-declarative task. - Declarative learning task: learning a list of paired words - Nondeclarative learning task: tracing a drawing through the reflection of a mirror (meaning the picture was reversed. They want to move the pen in a particular direction, but since it is reversed they needed to move it in the opposite direction. This required a period of time to improve the skill.) -

Bulimia Nervosa criteria

- episodes of binge eating - compensatory behaviors to prevent gaining weight that follow binge eating - critical evaluation of body weight or shape

Binge-Eating Disorder criteria

- episodes of binge eating - distress related to binge-eating - no use of compensatory behaviors

Environmental factors of Obesity

- fast food restaurants - ease of access to snack foods - fructose (type of sugar): doesn't stimulate insulin or leptin (satiety signals) Change in environment: college students experience this for example when they move from their home to campus - A study in 2012 by Small looked at the amount of fruit, vegetables, and exercise that college students consumed or engaged in over their four years. - between the 1st and 4th years: decreased fruit, vegetables, and exercise Food Deserts (certain areas) - low levels of fresh fruits available - increased consumption of fast and processed food

Lucid Dreams

- individual is aware they are dreaming - thought that the prefrontal cortex may be more active in these individuals during the lucid dream. - To test this hypothesis, Strumbreys et al. (2013) used a procedure called transcranial magnetic stimulation. The magnetic stimulation was replaced by transcranial direct current stimulation (tDCS).

Electro-oculogram (EOG)

- measure eye movements.

Anorexia Nervosa criteria

- restricted eating that leads to low body weight - fear of gaining weight - persistent behavior to prevent weight gain - disturbance in self-perception or failure to perceive seriousness of low body weight

Ramanathan et al. (2002)

- studied sleep deprived rats (animals with an extended period of wakefulness). - they found that this led to high levels of metabolic activity in the brain: produces free radicals. Oxidative Stress. - Damaging to neurons. - Conclusion: Low metabolic rate of SWS allows for removal of free radicals to protect the brain from damage.

Buchsbaum et al (1989) - focus on BRAIN

- studied the relationship between slow wave sleep and the metabolic activity of the brain. - SWS: decreased metabolic activity in the brain. (Important because it means there is a decrease in the activity of the neurons). - Conclusion: the brain is resting during SWS

Schwartz et al (2008)

- supported the role of the amygdala in narcolepsy. - the researchers were interested in studying the activity of the hypothalamus and the amygdala in response to emotional stimuli. - in the experiment, they were interested in positive emotion. - Participants were brought into a lab and were shown a series of humorous and neutral images. Researchers looked at their brain activity using the fMRI. They focused on the humerous response. When the humerous image was presented, they could see their hypothalamus showed a large increase in activity. - When they showed the same images, their amygdala was much less active. - For the patients with narcolepsy, the hypothalamus was only weakly activated, whereas the amygdala showed a much bigger increase in activity. In other words, the patients with narcolepsy showed a pattern opposite to the control group. - The results suggeste there is a relationship between the hypothalamus and the amygdala. - In individuals with narcolepsy, without orexin, because of that low activity of the hypothalamus, it is unable to inhibit the activity of the amygdala, and therefore theres a very strong response to the humorous stimuli by the amygdala.

Sleep apnea

- temporarily stops breathing - common cause: airway obstruction Treatment for Sleep Apnea: - surgery to remove obstruction - pressureized air forces airway to stay open (CPAP machine) - John has periods during the night where he stops breathing, causing carbon dioxide levels in his blood to rise. Once the levels get too high, he wakes up, gasping for breath. John suffers from sleep apnea. - A buildup of carbon dioxide in the blood is a characteristic of the sleep disorder known as sleep apnea

Mednick et al (2003) - consolidation of non-declarative memory

- tested participants on their ability to make visual discriminations. - data supported the role of REM sleep in the consolidation of non-declarative memory.

Flip-flop circuits

- the transition from awake to sleep and from SWS to REM sleep both involve flip-flop circuits (Reciprocal inhibition). - Another characteristic of Flip-flop circuits is only one component can be active at a time.

vlPOA (not sure this slide is necessary. I just added)

- vlPOA neurons receive inhibitory input from noradrenergic, serotonergic, and histaminergic neurons. - Electrical stimulation of vlPOA neurons produces signs of drowsiness. - The capacity of circuits involving the vlPOA and the locus coeruleus, raphe nuclei, and dorsal pons to show mutual inhibition may result in the alternation between sleep and waking.

Biological Clocks

1. Circadian rhythms: 24 hr cycle of sleep/wakign patterns 2. Seasonal rhythms: annual cycles Location of biological clock: Suprachiasmatic nucleus (SCN) - this is part of the hypothalamus, and once info about the light-darkcycle in the environment reaches this region, the SCN will then link behaviors to the light-dark cycle. - Ibuka and Kawamaur (1975): studied the role of the SCN in circadian rhythms. They produced SCN Lesions in rats, and then studied their activity levels and their sleep patterns. - Rats are nocturnal animals, so they're most active at night and sleep alot during the day. - In this experiment after the lesions, experimenters found that the animals still engaged in the same amount of sleep, so homeostasis was maintained. - However, the timing was disrupted. So now, the sleep periods are randomly distributed throughout the 24 hours period. SCN also secretes a protein called prokineticin 2 (PK2) - PK2 diffuses throughout the ventricular system of the brain, and then it activates receptors in the SPZ.

Medulla (in the brainstem)

1. Dorsomedial (AP/NST) and Ventrolateral regions within the Medulla: - medulla receives input from the vagus nerve (vagus nerve sends info from the stomach, duodenum, liver) - Medulla has its own glucose detectors The info from the vagus nerve and the glucose detectors within the medulla will activate the medulla when it is time to seek out food. 2. Lateral Hypothalamus: neurons that contain - Melanin-Concentrating Hormone (MCH) that if injected intraventricularly would induce eating - Orexin: if injected intraventricularly would induce eating

Other contributing factors that lead to development of an ED:

1. Genetics 2. Biological factors (premature birth) Theory: the progression of the disorder- 1. unknown genetic or biological factors (distorted perception of body weight?) 2. lead to starvation (restricted diet) 3. remaining symptoms will follow

PER / CRY (proteins synthesized) formation of Negative feedback loop:

1. Low level of PER/CRY gene activation - beginning in the nucleus, where we have to activate the gene that is responsible for coding PER and CRY. There are low levels in the cytoplasm of PER and CRY, and that activates CLOCK and BMAL1. CLOCK and BMAL1 are two gene activators. Messenger RNA for PER and CRY are produced. 2. PER/CRY synthesis - They leave the nucleus and enter the cytoplasm where the proteins PER and CRY are now produced. 3. High level of PER/CRY - When the levels of PER and CRY reach a certain threshold, they become high, they themselves will enter the nucleus, and they will inhibit the two activator proteins, CLOCK and BMAL1. 4. Inhibition of Gene Activators - step 3 with the inhibition of CLOCK and BMAL1 leads to an inhibition of more protein synthesis. So the levels of PER and CRY will drop again in the cytoplasm.

Flip-flop circuit integration (sequence of events)

1. Waking state - all 5 arousal systems are active (ACh, NE, 5-HT, Histamine, LH Orexinergic Neurons). - While the arousal system is active, it is also inhibiting the vlPOA. At the same time, the orexinergic neurons are activating the vlPAG, our REM OFF region. Norephinephrine and serotonin are also contributing to the activation of the vlPAG. The vlPAG then has a strong inhibition over the REM ON region during the awake state. As the waking period lengthens, adenosine accumulation increases and the vlPOA becomes active. Once the vlPOA is active, it will inhibit the arousal system: acetylcholine, norepinephrine, serotonin, and histamine. 2. Adenosine accumulation and removes the inhibition of vlPOA so the vlPOA is active: individual is now in Slow-Wave Sleep. - the vlPOA also inhibits orexin neurons. Therfore, the orexinergic input to the REM OFF is diminished, the REM OFF neurons become less active. As SWS progresses, NE and serotonin also decrease their activation of the REM OFF region. So all the excitatory inputs to REM OFF have been removed. Orexin is no longer activating the vlPAG, and NE and serotonin are no longer activating the vlPAG. The vlPAG then, is no longer inhibiting the SLD, the REM ON region. 3. NE, 5HT, Orexin decrease removing activation of REM OFF: REM sleep begins - The SLD can now activate the different brain regions that mediate the specific characteristics of REM Sleep.

What activates the Lateral Hypothalamus (LH)?

Arcuate Nucleus. - the neurons of the arcuate nucleus contain both NPY and agouti-related protein (AGRP), two other nueropeptides. What activates the Arcuate Nucleus then? - Ghrelin (bloodstream) - Medulla (in particular, NPY neurons in the medulla that have glucose detectors and receive input from the vagus nerve regarding low levels of glucose in the liver).

Seasonal rhythms (2nd biological clock)

Behaviors change as seasons change. The pathway associated with this biological clock: - light enters the eye and info is carried to SCN via the retinohypothalamic track. - Suprachiasmatic nucleus (SCN) - Paraventricular nucleus of the hypothalamus (PVN) - Spinal cord - Sympathetic Nervous system Neurons - Pineal gland - Melatonin secretion (by pineal gland) How does this pathway control seasonal rhythms? - Suprachiasmatic nucleus (SCN) sends info about the ambient lighting to the pineal gland. - Melatonin (Released by the pineal gland during the dark phase of the light/dark cycle so at night. Controls seasonal changes in hormones/beahvior). - Seasonal rhythms are under the control of melatonin secreted by cells within the pineal gland. - For animals that are seasonal breeders, they will experience anti-gonadal function during winter due to increased melatonin levels.

Neuropeptides involved in control of food intake and metabolism: CART and a-MSH

Cocaine and amphetamine regulated transcript (CART) - location of cell bodies: arcuate nucleus of hypothalamus - activated by Leptin - Physiological or Behavioral Effects: suppression of eating, increased metabolic rate a-melanocyte stimulating hormone (a-MSH) - location of cell bodies: arcuate nucleus of hypothalamus (colonized with CART) - activated by leptin - Physiological or Behavioral Effects: suppression of eating, increased metabolic rate; acts as agonist at MC4 receptors

Treatment of Eating Disorders

Cognitive Behavioral - success rate: less than 50% Pharmacological: - fluoxetine may help bulimia, but does not aid anorexia - LDX (lisdexamfetamine) may help binge eating disorder. Alternate therapies: under development - behavioral treatment targeting time needed to consume a meal - deep brain stimulation: cingulate cortex - oxytocin treatment

Drug treatments for Obesity

Drug Treatments: suppress appetite - targets for drug treatment under development included: 1. leptin 2. CCK 3. CART 4. MC4 receptors Drug Treatments: prevent digestion (decreased fat absorption) - Orlistat: helps maintain weight already lost -- GI side effects Drug Treatment: Combination - Naltrexone (opioid antagonist) - Bupropion (agonist)

Fasting phase of Metabolism

Digestive tract is empty Energy for the brain comes from glucose (which comes from two different sources at this stage): - Glycogen is converted into glucose in the liver - Triglycerides are converted into glycerol, then glycerol will be converted into glucose. Energy for the rest of the body is going to come from fatty acids: - Triglycerides in fat tissue will be converted into fatty acids. Triglyceride conversion into fatty acids and glycerol requires the Sympathetic Nervous system (SNS): - SNS activates adipose tissue (where triglycerides are stores) - SNS activates the pancreas (to produce glucagon) - SNS activates the adrenal gland (to produce catecholamines) - During the fasting phase of metabolism, the pancreas secretes glucagon rather than insulin.

Absorptive phase of Metabolism

Digestive tract is full Carbohydrates are converted into glucose - glucose levels in the blood increase, causing the release of pancreatic hormone insulin. - once insulin is present, glucose is available to all cells in the body. - Any excess glucose will be stored as glycogen in short term storage, or as a triglyceride in long term storage. Proteins in our diet are broken down into their constituent amino acids. - then they become available to be recombined through protein synthesis. - any excess amino acids will be taken up by fat cells and converted into triglycerides for long term storage. Fats from our diet are taken into the fat cells and they will be converted into triglycerides for long term storage. During the absorptive phase of metabolism, blood glucose levels rise, which triggers the release of insulin by the pancreas.

Circadian factors

Factors that limit wake and sleep to occur at specific times of the day.

Environmental Factors that signal to start a meal

Example: - time of day - sight/smell of food - sight of others eating

Behavioral Interventions used to treat Obesity

Exercise - burns calories - increases metabolic rate Relationship between stress and overeating may cause them to increase their weight again.

Genetics of Obesity

Genes can influence: - metabolism (2 types) -- Efficient metabolism: more fuel available in their long term storage reservoir. -- Insufficient metabolism: less fuel available for long-term reservoir - non-exercise activity (NEAT): activities such as fidgeting, spontaneously standing up and walking around, or changes in posture. - appetite level Twin studies: 40 to 70% of the differences in body fat are attributed to differences in genetics.

Neural Control of Sleep-Wake Transitions

Homeostatic factors Allostatic factors Circadian factors Flip-Flop circuits - Brain regions - Neurotransmitter systems

PYY and Leptin

Inhibit NPY/AGRP cells in Arcuate Nucleus Leptin - activates CART/a-MSH cells in Arcuate N. -- CART/a-MSH release --- Inhibit MCH and Orexin cells in LH

Physical Activity Factors of Obesity

Lifestyle (level of phsyical activity in one's lifestyle may not be enough to offset the number of calories consumed.)

Important Brain Regions in REM sleep: Striate and Extrastriate Cortex

Low activity in Striate cortex (aka the primary visual cortex) - no visual input High activity in Extrastriate cortex - visual hallucinations: DREAMS Low activity in Prefrontal Cortex - dreams are not well organized

Allostatic factors

Need to stay awake may modify homeostatic factors. - response to stress (mediated by hormones) - hunger (mediated by Orexin). - Ex: An animal may be very sleepy, but if it encounters a predator, the need to deal with the predator, avoid it and stay alive will be stronger than the need to sleep and the animal will therefore stay awake.

Slow-Wave Sleep (SWS) Disorders

Nocturnal enuresis (bed wetting) - Treatment: Behavioral intervention Somnambulism (sleep walking) - Remember that this is not acting out dreams becuase this is happening during SWS. Can occur in children and adults. Can be accompanied by complex behaviors such as eating food while sleep walking. If this occurs regularly the individual may develop sleep eating disorder. - Treatments: drugs that enhance dopamine function (dopamine agonists), and the drug topiramate which is an anti-seizure medication. Night terrors (pavor nocturnes) - this is not to be confused with a bad dream becuase it is occuring in SWS. The individual experiences a terror without the memory of what is causing the terror.

Chronic Sleep deprivation

Not getting enough sleep over an extended period of time, long term sleep deprivation - Chronic sleep deprivation can lead to obesity and diabetes.

Characteristics of REM sleep and Slow-Wave Sleep

REM Sleep: - EEG desynchrony (rapid, irregular waves) - lack of muscle tonus - rapid eye movements - penile erection or vaginal secretion - dreams Slow-Wave Sleep: - EEG synchrony (slow waves) - Moderate muscle tonus - slow or absent eye movements - lack of genital activity - imagery (non-narrative)

REM sleep flip-flop

REM flip-flop: - controls the time in SWS vs REM REM ON neurons (activates REM sleep) - located in portion of the dorsal pons called the Sublaterodorsal nucleus (SLD) REM OFF neurons (suppress REM sleep) - located in the ventrolateral periaqueductal gray matter (vlPAG) in the dorsal midbrain. Inhibitory GABA neurons connect (in both directions) the SLD and vlPAG regions

Control of REM sleep Components by REM-ON region

REM-On cells are actively inhibiting the interneurons in the spinal cord, causing paralysis during REM sleep. Causes paralysis during REM sleep. Purpose: Theory - the motor systems of the brain are rehearsing movements learned during the day without involving the msucles of the body. In other words, Nondeclarative Memory Consolidation.

Function of Sleep (SWS and REM) -

SWS: - allows the brain to rest after high levels of cognitive activity (remove damaging free radicals). - consolidates declarative memory REM: - promote brain development - consolidate non-declarative memory

Satiety Signals - Signals to STOP a meal

Short term signals: stop individual meals 1. Environmental factors (shorten or lengthen) 2. Sensory features of food (shorten) 3. Gastric factors (stomach) - nutrient detectors 4. Intestinal factors - a) duodenum detects fats: releases cholecystokinin (CCK), then: -- bile is released from gall bladder -- slows movement of food into duodenum -- CCK receptors (stomach/duodenum) activate Vagus nerve -- may also signal brain (safety signal) - b) Peptide YY (PYY) -- released by small intestines after a meal -- in proportional to calories consumed 5. Liver - glucose detectors - evidence: experimenters inserted glucose/fructose into hepatic portal vein resulting in a decreased food intake. 6. Insulin (when glucose levels are high) - Insulin receptors in hypothalamus - evidence: research in which intraventricular injections led to a decrease in eating. Long term Signal: Changes brain sensitivity to hunger and satiety signals 1. Leptin - hormone secreted by adipose tissue - Evidence: study of mice with a genetic mutation causing them to be without leptin are obese (Campfield et al. 1995)

Summarized Functions of the 6 Neurochemicals involved in the Neural control of Sleep and Arousal:

Sleep Regulation: - Adenosine Arousal Regulation: - Acetylcholine (ACh): cortical arousal, alertness - Norepinephrine (NE): vigilance - Serotonin (5-HT): ongoing movements - Histamine: novel stimuli - Orexin: exploratory behavior

Sleep/waking flip-flop (transition to sleep)

Sleep neurons of the hypothalamus: - Ventrolateral Preoptic Area (vlPOA) - Adenosine activates vlPOA. - vlPOA inhibits the arousal systems (via GABA neurons) - Causes sleep. Flip-flop circuits can be unstable. Orexin (5th arousal system): - acts as the stabilizer. Activates the fourth other arousal systems, biasing the individual towards waking. Factors which Activate Orexin: - Allosteric factors (hunger and thirst) - Circadian factors (biological clock will activate orexin during waking period). Factors which Inhibit Orexin: - Homeostatic factors (increased adenosine and vlPOA activity).

Obesity Treatments - Bariatric surgery

Sleeve gastrectomy - removes most of the stomach RYGB surgery - removes most of the stomach - takes remaining stomach and attaches it to lower level of the intestine - In 2005, Maggard evaluated the effectiveness of RYBG surgery and found that the avg weight loss 1 year later was 95 lbs. Participants felt less hungry, there was a decrease in ghrelin (decrease hunger), and an increase PYY (increase satiety) Risks of RYBG surgery: - Vitamin B12 and iron deficiencies - Smith et al. (2010) found other adverse effects at 30 days in 5.2% of patients including deep vein thrmbosis (blood clots), pulmonary embolism, nondischarge, and death

REM sleep behavior disorder

Symptoms: - dreams without muscle paralysis: acting out their dreams. Cause: - Damage to the REM regions - Hereditary: genetic neurodegeneration - occurs with other neurodegenerative diseases (e.g. PD) Treatment: - Clonazepam (type of Benzodiazepine. Works by enhancing the GABA system of the brain). a neurological disorder in which the person does not become paralyzed during REM sleep and thus acts out dreams - An effective treatment for REM sleep behavior disorder is the administration of the drug clonazepam. - A key symptom of REM sleep behavior disorder is a lack of paralysis during REM sleep. - REM sleep behavior disorder is the opposite of narcolepsy in that instead of muscle paralysis during waking hours, those with REM sleep behavior disorder lack muscle paralysis during sleep.

Long-term Reservoir - in adipose tissue

The long-term reservoir is in adipose (fat) tissue. Adipose tissue contains triglycerides, or stored fat. Used when short-term reservoir is being depleted. - fat cells convert triglycerides into fatty acids and glycerol. - liver cells convert glycerol into glucose

Astrocytes

The metabolism of glycogen within astrocytes produces adenosine, which in turn promotes slow-wave sleep. - astrocytes receive glucose from the blood vessel and then it delivers lactate to neurons. - the neurons will then take that lactate and convert it into energy. - Excess glucose will be store in the form of glycogen. If a person is awake for a long period of time, this glycogen will be needed so that the astrocytes will then convert the glycogen into lactate, and that lactate will again be delivered to the neuron. - Once that glycogen supply begins to deplete, that is when the astrocytes will begin to release adenysone which will then have an effect on neurons. That effect is that adenosine inhibits neural activity and this causes drowsiness. - The longer an individual is awake, the more they use up their stored glycogen, energy for neurons, and the more adenosine accumulates. So large accumulations of adenosine result in longer periods of time spent in slow-wave sleep. This then allows astrocytes to resupply their glycogen levels.

Retinohypothalamic Pathway

The neural pathway that carries info about the ambient lighting to the SCN is called the retinohypothlamic pathway, and it begins in the retina of the eye. - Photochemical in retinal GANGLION cells: Melanopsin. - sensitive to changes in light - axons of the retinal ganglion cells send this info about changes in light to the SCN

Short-term Reservoir - in Liver cells

The short term reservoir is in liver cells, and it involves two important pancreatic hormones: 1. Insulin (pancreatic hormone) - important in the conversion of glucose into its storage form of glycogen. - insulin is secreted when glucose levels in the blood are high, just after a meal - (In addition to converting glucose into glycogen, insulin is also important in allowing glucose to enter cells in the rest of the body, and it helps transport fats into adipose tissue.) Glycogen - stored glucose. 2. Glucagon (pancreatic hormone) - conversion of glycogen into glucose. - (Glucagon is secreted when glucose levels fall. In other words, after all the glucose from a meal has been used or stored.) Figure 12. 8: effects of insulin and glucagon on glucose and glycogen - We begin with glucose, a simple sugar in the bloodstream, after a meal. - Insulin takes glucose and converts it into glycogen, a complex insoluble carbohydrate that will be stored in the liver cells. - When blood levels of glucose are low, the hormone glucagon is secreted and it will convert glycogen back into glucose.

Causes of Eating Disorders

Theory that maybe symptoms are due to starvation? - eating disorders and starvation demonstrate 1. preoccupation with food and eating 2. ritualistic eating 3. hoarding food and other objects Is increase exercise intended to lose weight? Or a consequence of starvation? Rats given limited access to food did in fact increase their running wheel activity (smith et al. 1989)

Glucose (fuel) entry into cells

Transporter (a specialized protein on cell membranes) carries glucose across the cell membranes Glucose transporter: - on all cells of the body (except nervous system) requires insulin to carry glucose across the membrane. - nervous system cells (cells of the brain and spinal cord) do not require insulin. - (This distinction is very important. It ensures that the brain will continue to receive glucose between meals when glucose levels fall. When glucose levels are low, there is also no insulin in the bloodstream. Therefore, glucose will not be delivered to the cells of the rest of the body, but glucose will still be delivered to cells of the brain.) Source of fuel for all cells except NS: - glucose and fatty acids Source of fuel for NS cells: - glucose - In the experiment by Tordoff and Friedman (1988), reduced eating in a hungry rat was noted after infusions of glucose or fructose into the hepatic portal vein. - Cells of the liver convert glucose into glycogen.

The "ticking" of the biological clock

What allows the Suprachiasmatic nucleus (SCN) to mark intervals of time? (remember, the internal clock still functions even without changes in ambient external lighting). - The answer comes from the pattern of activity within individual neurons. (in other words, the time it takes individual neurons to produce, and then degrade, a set of proteins that are called PER/CRY. - They form a negative feedback loop within the neuron. Simplified explanation of the molecular control of the daily "ticking" of neurons of the SCN: 1. Protein synthesized (The gene is active. messenger RNA leaves the nucleus and causes the production of protein.) 2. High levels of protein inhibits synthesis (The protein enters the nucleus, suppressing the gene responsible for its production. No more messenger RNA is made.) 3. Low level of proteins initiate synthesis (The level of protein falls, so the gene becomes less active again). ***Michael Rosbash, Michael Young, and Jeffrey Hall played a major roll in discovering this mechanism and received a Nobel Prize in physiology or medicine in 2017*** - possible bonus question. Don't have to know.

Eating: Metabolism

Why we eat: - to provide fuel (energy) for our body and building blocks for maintaining our organs. Metabolism: - the chemical reactoins in cells that carry out these functions. - 2 phases: - Absorptive phase (just after a meal) - the source of fuel is in the digestive tract itself. - Fasting phase (digestive tract is empty) - source of fuel now comes from stored carbohydrates in the short term, or stored fat in the long term.

Flip-flop impairment in narcolepsy

Without Orexin: - the decreased activation of the 4 other arousal systems leads to intense daytime sleepiness. - the decreased activation of the REM OFF region (vlPAG) leads to cataplexy (muscle weakness or paralysis). One more brain region that is important in narcolepsy is the Amygdala. - increased emotion activates the amygdala. - When amygdala activates, it activates the REM-ON (SLD) in the absence of orexin (which would usually inhibit the REM ON region). - This is what triggers a Cataplexic episode.

Fatal Familial insomnia

a fatal inherited disorder in which individuals suffer damage to their thalamus. - Causes chronic sleep deprivation, as well as impairments in paying attention, in their memory, a loss of control over their autonomic nervous system and their endocrine system meaning possible elevated body temp or weight loss. - Death occurs about 12 months after onset. While chronic sleep deprivation is a very important characteristic of this disorder, its not clear if that is the actual cuase of death. So the actual cause of death is unknown. - Animal studies do show, however, that prolonged sleep deprivation does result in death. These animals also experience a loss of temperature regulation, a loss of weight, and when death occurs there is no identifiable inflammation or organ damage to explain this outcome.

Metabolic Signals

a) Glucoprivation - having low glucose levels. Will signal the onset of the next meal. b) Lipoprivation - having low lipids (fatty acids) in the blood. Will signal the onset of the next meal. Detectors for both Glucose and Lipids: - Brain: glucose - Liver: glucose and fatty acids (If levels are low, this info is sent to brain via Vagus nerve.) Figure 12.13 - Nutrient Receptors for Glucose and Lipids in the Liver and how they arrive at the brain - Nutrients from a meal are carried from the intestines to the liver, through the hepatic portal vein. - If it's been a period of time since the last meal, nutrient levels will be low. - There are detectors in the liver for glucose and lipids, and when it's determined that glucose and lipid levels are low, these detectors will activate the vagus nerve. - The vagus nerve will then send a message to the brain to initiate the next meal. - Remember, there are also glucose deterctors in the brain which can directly determine low glucose levels. *** The important interal hunger signals we have discussed then are increases in ghrelin, and decreases in glucose and fatty acids, or lipids.

metabolic pathways during fasting and absorption

ch. 12 pt 1 end of vid

brain changes from anorexia

patient with anorexia nervosa showing enlarged sulci, third ventricle, and lateral ventricle.

MC4 receptor (in the lateral hypothalamus)

receptor for Leptin in hypothalamus region of the brain - a-MSH binds to MC4R and suppresses eating - AGRP also binds to MC4R and induces eating

Electromyogram (EMG)

recording of facial muscle movement