Neurobiology Module 9

Structure of cerebral cortex

If we look at structure of cerebral cortex itself, neurons are aligned next to each other. This summation results in extracellular field potentials that are theoretically parallel to the dendritic tree of the pyramidal neuron. Can summate across multiple neurons. Further, the parallel arrangement of pyramidal cells in the cerebral cortex allow these fields to summate across a population of simultaneously active neurons. Creating a large enough electrical field allows it to be recorded at the level of the scalp. See that there are a number of tissues that the electrical field must penetrate in order to be recorded by the electrode on the surface of the scalp. Protective tissues of the brain, skull is biggest blocker of electrical current. The dead skin under scalp also provides a lot of resistance. Synchronously active neurons so the electrical field can summate together and we can record an EEG? Somewhere between thousands and millions, less of a requirement is the EEG is going to be recorded directly from the surface of the brain

Consequences of neuron shape for the summation of electrical fields

Important to remember what pyramidal neurons are. Look at summation across space of these postsynaptic changes in electrical potential. Theoretically, it is mainly in pyramidal neurons where these things add together in such a way that we see large enough electrical fields for brain activity without using a single unit recording (inserting a microelectrode into the neuron itself). The dendritic trees of pyramidal cells are shaped such that electrical fields from post-synaptic potentials have a greater ability to sum together across the neuron. Usually the stellate cell (another common neuron of the CNS), electrical potentials coming from all different directions to cancel one another out. But for pyramidal neuron, aligned down long central branch of the dendritic tree and can summate. Relatively large electrical fields. Some possibility it can be recorded without penetrating the neuron itself

Neural mechanisms of sleep and wakefulness: the ascending reticular activating system

ARAS. Found through experimentation with animals that would cause them to remain unconscious. General concept proposed by Moruzzi and colleagues (1940s-1950s) due to loss of consciousness induced by brainstem lesions. Contains many of the nuclei already discussed as components of diffuse modulatory neurotransmitter systems: PMT complex (ACh; brainstem center of the cholinergic diffuse modulatory system), Dorsal raphne nuclei (5-HT; for serotonergic signaling to regions of the cerebral cortex and connects down the spinal cord), Locus coeruleus (NA; origin for noradrenergic signaling in the brainstem). All of these nuclei part of the ascending reticular activating system Induces: reticular formation- "net" of neuronal structures rather than dense nucleus. Extends across midbrain, pons, and medulla. Reminder: origin of reticulospinal tract (descending motor pathway involved in automatically maintaining an upright stance and being able to override it to voluntary control our posture). Extends across an extensive proportion of the brainstem

REM sleep

Also called paradoxical sleep. Some states of this sleep would never be seen in the waking state. Mainly in the early morning. Eyes move rapidly in bursts. Highly active brain, wake-like EEG. Very hard to distinguish from waking. Need other ways to measure. Brain metabolic rate higher than waking state. Vivid, complex dreams (esp. during bursts of eye movement). Can act out our dreams. Body is paralyzed, nearly complete loss of skeletal muscle tone. "paradoxical sleep." High level of brain activity while the rest of the body is shut off. High sympathetic nervous activation. Higher heart rate, higher respiration. Thermoregulation temporarily shuts off. Some very basic aspects of homeostasis are shut off. Higher HR and respiration (irregular)

Functional states of the healthy brain

Awake: active brain, movable body. Non-REM sleep: idling brain, moving body. Rate of brain activity decreases with increasing depth. Not a lot of information transmission. High amplitude, low frequency. Body can still move like when in waking state. REM sleep: active brain, paralyzed body. Brain is active as it is in waking state. Brain not responding to external stimuli, only internal stimuli (dreams)

EEG rhythms in general

Certain states have dominant rhythms. The lowest range of EEG rhythms we observe are delta. Anything lower than 4 Hz. 4 peaks in a second. In a healthy individual, only dominates when the person is in deep sleep. Also seen in patients in comas. Next higher rate of EEG rhythms is theta. 4-8 Hz. Healthy individual seen in drowsiness, light sleep, and REM sleep. Alpha is between 8-12 Hz. Typical of waking EEG. Wakefulness, relaxation, drowsiness, and eyes closed. Beta is also a common feature of normal, waking EEG. 12-25 Hz. Active wakefulness and focus. Gamma range of EEG activity, never dominates the EEG. 25-70 Hz. Component of wakeful, normal EEG. High gamma. Cannot be measured at the surface of the scalp in adults. 70-150 Hz. Measured intracranially and in very young infants

Influences and origins of circadian rhythms

Circadian rhythms: vary on a cycle of approx. one day. Observed in almost all land animals. Cycles of behavior and physiology. In the cells too. Physiological and biological processes, not just behavior. Continue in the absence of explicit lightness/darkness cues. Environment cues that influence the circadian rhythm. A number of different physiological function measures that are varying on a circadian rhythm. Can look at alertness, body temperature (reaches minimum during the night), growth hormone (maximum during sleep), cortisol (stress hormone; highest in morning and decreases during the day), potassium secretion by kidneys (mainly in daytime). Operate even in the absence of light. Without cues, or under artificial cues: behavior and physiology can decouple. Physiology: roughly 24 hour cycle. Behavior: up to 30-36 hour cycle (wake: 20 hours, sleep: 12 hours). Tend to continue on 24 hour rhythm, regardless of the external cues being provided. However, behavior changes considerably. Can ended up operating on a much longer cycle (feels normal). Cues induces synchronization, not rhythmicity (intrinsic to cells of the body and brain). Desynchronization can compromise sleep quality (between patterns of sleep and wake; physiological circadian rhythms)

Reminder: neural circuitry for rhythmic firing

Continuous excitatory input is translated into rhythmic activity via inhibitory interneurons. Activity in two excitatory interneurons alternates. An excitatory interneuron that has been firing for a while will be inhibited by incoming feedback. Another possibility from our section on movement. Could be some circuitry in the connections between neurons (instead of being intrinsic to the neuron itself) that is imposing a rhytmic pattern of firing

Reminder: circadian variation in cortisol release

Cortisol levels are highest at the beginning of the day and after meals

Sleep deprivation and its consequences

Cumulative effects: distractability, unforgiving, difficulty thinking clearly, social disinhibition (drunk). After about one night of sleep deprivation. More than one night. Greater difficulty with social interactions, reduced self-control, increased drive for food and sex, aggression, compromised immune function (couple nights), painful joints. Extreme sleep deprivation. Dysfunction in CNS. Difficulty with thermoregulation (body temperature drops), physical weakness, hallucinations, paranoid delusions (rare; even for a mentally healthy person). About 1/3 adults in America are sleep deprived. If left unchecked, linked to many potentially lethal health outcomes: cardiovascular disease, cancer, stroke, diabetes, hypertension. Sleep deprivation alone is not the sole cause. Increased risk of accidents on the road, falling asleep when driving

EEG patterns in comatose patients: delta rhythms

Delta dominating the EEG with very high amplitude behavior. Very slow. Not many peaks within one second of time. Delta could precede an improvement or deterioration of their state. Have to see what is going to happen next

Reminder: classifying neurons, other classification schemas

Dendritic tree shape: stellate cell and pyramidal cell. Always looking at pyramidal neuron morphology. Connections. Incoming sensory info: sensory neuron. Outgoing motor info: motor neuron. Between neurons: interneuron. Axon length: pyramidal is Golgi type I or projection neuron. Stellate is Golgi type II or local circuit neuron. Gene expression

Reminder: classes of neurons in the lateral hypothalamus involved in feeding regulation

Distinguished by peptide neurotransmitter produced. Widespread effects in brain. Both: have widespread connections in CNS. Are promoted by reduced leptin levels. Are associated with increased feeding behaviors. MCH neurons: many monosynaptic connections to most of cerebral cortex. Prolongs consumption during a meal. Orexin neurons: initiates feeding (meal initiation)

The functions of sleep and dreaming cont.

Dreams are impossible to measure objectively. Research on function of dreaming study REM sleep instead. REM sleep deprivation induces accumulated need. Waking people up right when they hit REM sleep. REM rebound: relative increase in REM (vs. total sleep) following deprivation. The next night, enter REM sleep earlier. Physiological pressure/need for REM sleep that accumulates when you are selectively deprived of it. Activation-synthesis hypothesis of dreaming: memories and associations stored in cerebral cortex are activated by discharges of pontine neurons (via thalamus). Cortex works to synthesize these disparate neural events into a sensible whole. During REM, see bursts of activity in the pons. Activity propogates to the cortex via the thalamus. Results in activation of existing associations in the cortex. Representation of objects, memories, places. Random which aspects of restored memories are going to be activated by a given pontine burst. Cortex works to synthesize this information to create a narrative. Cannot explain recurring dreams of complex, full stories (above theory says period of activation is random). Does not seem to explain our dreaming experiences

EEG patterns in comatose patients: burst suppression

EEG help a lot to decide a level of care for patients that are unresponsive. Burst suppression is when there is a period of time where there is a burst of oculatory brain activity, and then it is suppressed. Then, will see another burst. Predictive of poor outcomes or potentially death, a vegetative state. Really negative sign. Might be preceded by delta

Human electrophysiology

Electroencephalography (EEG). Electro: electricity (measuring electrical activity in the brain). Encephalon: brain. -graphy: writing. Writing and collecting the electrical activity of the brain. Electromyography (EMG). Recording the electrical activity of muscles. Electro-oculography (EOG). Electrical signals associated with the eyes. Electrocardiography (ECG). Electrical activity associated with the heart

Reminder: a cellular mechanism for rhythmic firing

Excitatory activation via NMDA receptors allows both Na+ and Ca2+ entry. Cell depolarizes, firing occurs. Ca2+ entry opens Ca2+-activated K+ channels. Cell hyperpolarizes, inactivating NMDA channels. Cell returns to resting potential, and NMDA channels are again ready for activation. Have talked about rhythmic firing in the spinal cord for the generation of motor patterns. Creating periods of time of unresponsiveness

Extreme sleep deprivation: the stories of Randy Gardner and Peter Tripp

Extended periods of sleep deprivation. Pretty well-studied during. Randy Gardner record: 264 hours. High school science fair project. Set world record. Examined by emerging sleep experts at the time. Extremely unpleasant experience, hallucinations. Slept a lot and recovered, returned to normal functioning. Shouldn't read too much into the resilience of the human brain following sleep deprivation. Peter Tripp record: 201 hours. Did not recover. After attempt (8 days), never returned to normal psychological functioning. Extreme consequences of sleep deprivation

Petley's own EEG using eyes open and eyes closed

Eyes open, EEG dominated by fairly high frequency activity. Low amplitude peaks that are varying quite quickly with time. Not much alpha. As soon as she closes her eyes, can see a much higher amplitude level of activity and a low slower. Alpha

Polysomnographic features of the sleep cycle cont.

Figure of brain rhythms and what they look like. Stages all look very alike. Can be very difficult to sort through. Key feature of REM sleep is the absence of muscle tone. If not paralyzed, going to have a certain level of tension in the muscles (even if not necessarily contracting them). No tonus. Clear EEG features of stage 2 non-REM sleep. Have a huge K-complex. Burst of high frequency activity called a spindle. Getting into slow-wave sleep of non-REM (stages N2 and N3, or stage 3 and 4). High amplitude, low frequency activity. Delta range of EEG bands. Higher and higher proportion of time experiencing Delta waves (biggest difference between stage 3 and 4 non-REM)

Changes in sleep across the lifespan

From childhood to adolescence. Total sleep time and percentage of slow-wave sleep decrease. Increased percentage stage 2 sleep (typical of adult sleep patterns) and earlier REM sleep onset. Total sleep time decrease only observed for recordings made on school days. For adolescents, start to fall asleep later at night and get up early (probably sleep deprived). From early to older adulthood: all aspects of sleep affected. Reduced total sleep time, sleep efficiency (greater tendency to wake up in the night), percentage of slow-wave sleep, percentage REM sleep. Longer time to fall asleep, more percentage stage 2 sleep. ~10 minutes less sleep per decade of life. Total sleep time may not decline beyond 60 years of age. Also takes longer for us to fall asleep

Polysomnography

Going to a sleep lab to undergo a sleep study. Looking at sleep and deciding to diagnose a sleep disorder. Respiratory or neurological in nature. Many types of sensors. Polysomnography includes: EEG, EOG, EMG, ECG. Respiratory measures, like abdominal and thoracic excursion (bands around chest and stomach, how much body is expanding), oximetry, nasal pressure. Body position sensor, snore volume. Video recording

Abnormal oscillatory firing: seizures

Happens in epileptic seizures. Extensive feedback circuitry of cerebral cortex makes it vulnerable to excessive synchronized excitation. Allows different regions of cortex to work together (one to influence the other). Whether it be from higher order cortex to lower. Comes at a cost, cerebral cortex can be close to over excitation (fairly easily). So, in the case of people that have epilepsy, there is excessive abnormal excitation (can be debilitating to their lives). Seizure: pathological synchronized activity across all or a portion of the cerebral cortex. 7-10% of people have at least one in their lifetime. To have epilepsy, must experience them repeatedly. 0.7% of people experience them routinely (epilepsy). Many possible causes. Increased excitability due to abnormal Na+ channels (much more excitability). Increased excitability due to inadequate GABAergic (most common inhibitory) neurotransmitter (synthesis, transport, release, or receptors). Many possibilities that can lead to this overexcitation of cerebral cortex. On an EEG, see pretty normal brain activity before and after. During seizure, very high amplitude, lower frequency activity. Lots of synchronization, a lot of neurons are firing at the same time

Studying sleep

Hard to know what technology to use. When sleep science emerged, only one type of technology to study brain function in an alive human was EEG. When other technologies came out (PET, fMRI), are they compatible with the person sleeping. Certainly fMRI is not and is loud and uncomfortable. PET has been applied to look at regional changes, blood flow, and cerebral metabolism during sleep deprivation and actual sleep. However, most of our understanding is from EEG

The functions of sleep and dreaming

Hard to pin down physiologic purpose of sleep. Theories of Restoration: sleep provides a period of rest and recovery. Preparation to awake again (restoring some capacity to recover from something that happened during wakefulness). Failures to support these theories: no toxins made during waking which is destroyed during sleep. Unclear what is restored. Theories of Adaptation: reduce risk of predation or other harm. Conserve energy. Evidence: energy usage during sleep is the minimum to stay alive. Saying it doesn't necessarily restore anything

The intracellular timing mechanism of SCN neurons

How are neurons of suprachiasmic nucleus accomplishing this goal of maintaining a strong internal circadian rhythm. Many species show cellular circadian rhythms. Genes controlling circadian rythmicity are known as clock genes. Using many fruit flies. Examples of clock genes (mammals): period (per), cryptochrome, and clock. Variants of all of these. Clock genes produce proteins that inhibit their own transcription when they enter the nucleus. Have a protein being produced and when that protein makes its way into the nucleus, it prevents production of that protein. Inhibiting itself. Amount of time necessary for this cycle to be carried out is the circadian rhythm. Takes about a day. Genetic transcription is highest/protein levels are lowest in the nucleus around midday. Genetic transcription is lowest/protein levels are highest in the nucleus in the middle of the night

Neural mechanisms of sleep and wakefulness: general principles

How does brain control what stage of sleep we are going to be in. Transitions. The diffuse modulatory neurotransmitter systems (in the brainstem) are crucial for controlling sleep onset and the stages of sleep. Noradrenergic, serotonergic, cholinergic. Especially: norepinephrine and serotonin: wakeful stage. Acetylcholine: different subpopulations (different parts of origin) crucial for REM, others more active during waking. Influence rhythmic firing of thalamus that block sensory information flow to cortex. Different parts of sleep that make us more or less susceptible to stimuli. Modulatory systems important for input into the thalamus to determine whether the thalamus will send information on to the cortex. Additional descending inhibition blocks motor output during REM. Do not want motor output during REM sleep

Biological clocks of the brain: the suprachiasmic nucleus

One structure that shows the most evidence for acting like a biological clock. Two tiny nuclei just above optic chiasm. Part of the hypothalamus. All neurons of SCN express strong rhythmic activity and changes in metabolism on a circadian cycle. Rythmic patterns of activity in those suprachiasmic nucleus neurons is influenced by patterns of environmental light cues. Possible by input from the retina. Targets of retinal ganglion cells other than those in the superior colliculus and the thalamus. Receptors are that sensitive to light in the retina are retinal ganglion cells. Small tract that is part of optic nerve conveys lighting into to suprachiasmic nucleus. Receives input from photosensitive retinal ganglion cells to entrain to environmental lighting levels. Via retinohypothalamic tract. Respond to general luminance, not detailed aspects of vision. General information about lighting levels. Lesions abolish circadian rhythms, but not sleeping altogether. Sleeping will occur to light-dark cycles if present. Damage to suprachiasmic nucleus, see circadian rhythms of being being abolished. Will still sleep, but not consistent with a circadian rhythm. Other mechanisms available for controlling the sleep cycle. Animals can use cues in terms of lighting to regulate sleep and wake

Reminder: signals involved in feeding regulation

Orexigenic signals: promote feeding behaviors. Satiety signals: reduce feeding behaviors

Neural mechanisms of wakefulness: orexin and excitation of the thalamus

Orexin (aka hypocretin): hypothalamic peptide neurotransmitter crucial for wakeful alertness. Produced by lateral hypothalamus. The most important neurotransmitter for wakefulness. Axons of orexin-ergic neurons (that produce orexin) project widely throughout brain. Strongly excite cholinergic, noradrenergic, serotonergic, dopaminergic, and histaminergic (induce sleepiness when blocked) modulatory systems. Excites other neurotransmitter systems that are active during wakeful state. Promotes wakefulness. Inhibits REM sleep. Facilitates certain types of motor behaviors. Involved in regulation of neuroendocrine system (hormone secretion) and autonomic nervous system

Neural mechanisms of wakefulness: orexin and excitation of the thalamus

Other modulatory neurotransmitter systems fire at their maximum rate in anticipation of waking and/or during arousal: locus coeruleus, brainstem and (basal) forebrain nuclei of cholinergic system, and midbrain histaminergic nuclei. Effect on thalamus very important. Collectively synapse directly on entire thalamus, cerebral cortex, and many subcortical nuclei. Promote excitation. Suppresses rhythmic firing (esp. by thalamus). Firing in a way that allows sensory information to reach the cortex. Ensure thalamic relay of sensory information to cortex. Wakeful state characterized by high levels of orexin, serotonin, noradrenaline, acetylcholine, dopamine, histamine. Have physiological factors that will induce body into state of sleep

Intracranial EEG: electrocortiography (EcoG)

Performed not in healthy individuals. Portion of brain surgically removed to treat epilepsy or to remove a tumor. Some of our best understanding of how the human brain works comes from patients undergoing this kind of monitoring. Direct access to the functioning of the brain

The sleep cycle

Peter Tripp experienced hallucinations. Within 90-minute period, should go through non-REM sleep, one cycle of REM sleep, and then into next sleep cycle. All 4 (actually 3) stages of NREM and REM sleep experienced within roughly 90 minute cycle. The sleep cycle, and other cycles that operate over a period shorter than a day are called ultradian rhythms. Hypnogram, typical way to convey what sleep has been like. Stage 1 is lightest stage of non-REM sleep (still looks a lot like waking state). Reach deepest sleep in stages 3 and 4. Then come back up through stages to reach REM sleep. Tend to skip stage 1 when progressing back through non-REM sleep after REM. Typically in first half of the night. In second half of night, might not reach these deep sleep stages. Instead, going to sleep a progressively longer amount of time in REM. Spend the most time in stage 2 of non-REM

REM sleep

REM sleep is paradoxical and very unusual. Cortex active much like in the awake state. Reduced activity in frontal lobe. Extrastriate visual areas (associated with processing more complex features) of visual input much more active than in wakeful state. Dreaming. NE and 5-HT activity are minimal prior to REM onset. Subpopulation of cholinergic neurons in brainstem neurons appears to induce REM sleep (REM-on cells). Ascending and descending connections: ascending is thalamus, promoting wake-like cerebral activity (but sensory information still not making its way to the cortex). Some regions more active than wake, others less active. Desceding is motor pathways, induce paralysis. Important to make sure that we do not act out our dreams. Extrastriate visual areas especially active. Frontal lobes considerably less active

Practices for good sleep hygiene

Regular hours of bedtime and arising. Do not eat heavy meals near bedtime. Avoid napping during the daytime. Exercise in the late afternoon or early evening. Minimize caffeine intake and cigarettes smoking within 8 hours of bedtime. Don't look at the clock during the night. Write down worrisome thoughts, then let them go. Keep a comfortable temperature in the bedroom. Slightly cool is better than slightly warm. Do not use alcohol as a sleep aid

Reminder: synaptic integration

Remind ourselves of what happens with synaptic integration. When synaptic neurotransmission happens. In particular, in postsynaptic membrane, EPSP or IPSP for ions. When we are measuring EEG, essentially seeing the summation of these postsynaptic phenomena

Effects of sleep restriction as shown on the MSLT

See that reduction in sleep onset on the MSLT as a function of sleep restriction. See that participants were restricted to only 5 hours of sleep per night. Progression from 1 day to 7 days. See that increase in sleep restriction, leads to a reduction in sleep onset on the MSLT. See fastest level of sleep onset with the highest amount of restriction

Polysomnographic features of the sleep cycle

Sensors around the eye to look at eye movement. Sensors of the chin to look at muscle activation. Super important for being able to distinguish REM sleep. Then, EEG sensors on the top of the head for looking at changes in brain rhythms

Oscillatory activity of thalamic pacemaker cells

Similar pattern of firing as seen in the spinal cord. Pacemaker cells of the thalamus have special ion channels that allow them to generate rhythmic firing even in the absence of excitatory input. Have their own intrinsic mechanisms within the neurons that is going to create periods of time where they will fire and will not fire. See in example that the neurons are being artificially stimulated using a current in way that the thalamic pacemaker cell will have a burst of action potentials and then cell membrane will hyperpolarize and be unresponsive. These neurons are capable of generating this rhythmic activity even in the absence of stimulation. Can be the point of origin for the bursting and slow oscillatory activity

Scalp-recorded EEG

Since the intervening tissues (meninges, skull, muscles, and skin) provide resistance against current flow (and making it more difficult to record the EEG), more neurons must be synchronously active for the EEG to be measured from the surface of the scalp. Thousands to millions of neurons must be synchronously activated for activity to be recorded at the scalp. Fields need to act together

The functions of sleep and dreaming

Sleep deprivation leads to cognitive deficits. Sleep may have special importance for learning (REM sleep). Sleep improves recall (vs. equal period of time without sleep). "Memory consolidation." Patterns of neural activation observed during learning replayed during sleep (rodents). May be part of memory consolidation process. Special relevance of REM in learning: duration of REM increases after intense learning experiences. Some tasks only improve after sleep if REM is experienced. Special relevance of stage 2 non-REM (N2) in memory consolidation: spindles may reflect integration of information between hippocampus and cerebral cortex (via the thalamus). May be especially important for verbal memory retention. Words lists with better recall demonstrated more stage 2 non-REM

Why do we sleep?

Sleep is observed in all mammals, birds, and reptiles. Some very fundamental physiological requirement for sleep. REM only seen in mammals and some birds. Not necessary for other animals. Sleep need: ~3-18 hours/day. Most likely need relates to brain function. First deficit following sleep deprivation. Grazing animals sleep the least. Like 3 hours. Predators sleep the most. Remarkable adaptations in some animals requiring long-term locomotion: dolphins and whales must swim continuously. Birds that fly for prolonged periods (swifts, frigatebirds, etc.)

How do we define sleep?

Sleep: a readily reversible state of reduced responsiveness to, and interaction with, the environment. Note its differentiation from: Coma: sometimes irreversible. Not readily reversible. General anaesthesia: reversible only after anaesthesia wears off

Subjective measures of sleepiness

The Stanford Sleepiness Scale (SSS). How sleepy are you. Very simple. Just choose one of the descriptions that matches your correct state. Will indicate how sleepy you are

The intracellular timing mechanism of SCN neurons

This process of circadian rhythm regulation by clock genes is happening individually in each one of the neurons of the suprachiasmic nucleus. Each one of these neurons is essentially acting like a little clock. Synchronization provided by retinal input, indicating environmental cues of light and dark. Otherwise they are all kind of drifting and acting on their own

Falling asleep and non-REM sleep

Transition to sleep involves reduced activity in wake-promoting modulatory neurotransmitter systems (ACh, NE, 5-HT). Distinctions within populations that produce acetylcholine. Subset of cholinergic neurons in brainstem increase activity with non-REM sleep onset. Rhythms of non-REM sleep generated (in part) by thalamus. Consequence of changes in the neural signaling of neurons in the thalamus. As we progress through phases on non-REM sleep. High amplitude, low frequency as we get farther into stages of 3 and 4 in the EEG. Bi-directional excitatory connections permit rhythm propagation between thalamus and cortex. Rhythms can originate in either one of these places. Largely originate in thalamus, but other places too

Neural control of the sleep cycle

Increased activity during REM sleep. REM-on cells. Look at patterns of connections in the brainstem that are associated with the cycling between non-REM and REM. Increased activity in REM state for REM-on neurons. Also have REM-off cells that are not cholinergic, noradrenergic, or serotonergic. Show higher level of activity at the end of the REM state. Activity then decreases to permit REM to happen again. Cyclic alternation between REM and non-REM sleep. Combination of excitatory and inhibitory between populations of neurons. Gradually leading to either excitation or inhibition. Have cholinergic neurons in the brainstem reticular formation that are REM-on neurons. They are exciting the REM-off population and also exciting themselves. As soon as REM starts, there is a rapid increase in cholinergic activity (associated with REM period). However, during duration of REM, the REM-off neurons are being gradually excited. Reach a certain point (of excitation) when they will shut REM off through inhibitory connections. REM-off neurons use serotonin and noradrenaline. REM-off neurons also inhibiting themselves and will eventually reach a level of inhibition where REM is allowed to start again

Special features of stage 2/ N2 sleep

K complex is a huge deflection in the EEG that kinda comes out of nowhere. Seems to be in response to sensory stimuli (like a tap on a wall). Seems to be an inhibitory mechanisms that tries to stop the sensory information from reaching the cortex and waking up the individual. Habituate very rapidly so if you knock on the wall several times in a row, will stop seeing a K complex. Can occur by themselves or for this example, with some high frequency activity on the tail end (those are these sleep spindles). Sleep spindles look like a spindle of yarn. Seem to reflect processing loops between cerebral cortex and thalamus

Non-REM sleep

Majority of sleep. Most of what we experience in a night of sleep Multiple phases: formerly stage 1-4 (now N1-N3). Now say there are only three stages. Eyes move slowly if at all. Dreams, if any, are neither complex nor vivid. Body muscle tension reduced (vs. waking state), little movement. Often shift body. Lowered body temperature. Increased parasympathetic activation: reduced HR, respiration, kidney function, increased rate of digestion. Slower rate of oscillations, higher amplitude oscillations with increasing sleep depth. N# = "deep sleep" or "slow-wave sleep". Most sensory input does not reach cortex. Seeing highly synchronized activity. No opportunity to convey sensory information. Body and brain appear to rest- reduced metabolic rate (in the body and the brain)

Sleep-promoting factors

Many sleep-promoting substances have been identified. Chemicals that build up in the body and central nervous system that are associated with periods of time spent awake. Adenosine: molecular building block for DNA, RNA, and cellular energy storage (ATP). Also used as neuromodulator by neurons and glia. Neuromodulator: a neurotransmitter (kinda) that has no effect by itself, but modulates induced neuronal activity. Influences a neurons response to other neurotransmitters. There are adenosine receptors. Extracellular levels increase during wakefulness (esp. sleep-related brain regions), decrease during sleep. Inhibits modulatory neurotransmitter systems that promote wakefulness (ACh, NE, 5-HT). Receptor antagonists promote wakefulness. Drugs that prevent adenosine from exerting effects, we will promote wakefulness (like coffee and tea)

Biological clocks of the body and their entrainment to the SCN

Most cells of the body show a circadian rhythm (besides those neurons in the suprachiasmic nucleus). Provide some level of circadian rhythm. Under normal circumstances, entrained to SCN. SCN provides synchronizing for all of those other mechanisms. Many mechanisms. Many pathways for how information is conveyed from the SCN. SCN influences activity of the autonomic nucleus. Widespread neural connections (mainly inhibitory) to: other parts of hypothalamus (feeding, metabolism, body temperature, cortisol secretion), midbrain, and other deep structures of the cerebrum. Reduction of temperature itself is valuable for synchronizing circadian rhythms of the rest of the body. See cyclic variations in secretion of cortisol. Circadian rhythms for feeding behaviors and metabolism. SCN targets many parts of hypothalamus, lots of inhibitory. Vasopressin secretion from the SCN itself.

Reminder: cytoarchitecture of the cerebral cortex

Most of the cerebral cortex is neocortex (6 layers). Older regions have less layers. Each layer contains cells with similar size, shape, inputs, outputs, density. Layer I has no neurons. Motor cortex: small layer 4 (input from deep structures) and large layer 5 (output to deep structures). Sensory cortex: larger layer 4 and smaller layer 5. Many pyramidal neurons found in layer 5

Sleep in the bottlenose dolphin

Must always be using locomotion. One hemisphere of the brain is asleep at the time. Alternation. Sleep very high amplitude, low frequency peaks. In humans, indicative of deep sleep. Do not see REM sleep in dolphins

Additional factors in the physiological control of sleep

Must talk about sleep with circadian rhythms. Not just a function of how long we have been awake in regard to how likely we are to fall asleep. Times of day, even when we are sleep deprived, that we are less likely to fall asleep. The Borbely Two-Process Model of Sleep Regulation. Two processes that influence likelihood to fall asleep. Process S is essentially how long you have been awake. Under normal circumstances (you are sleeping each night), will reach a peak right before you fall asleep. Attenuate over the night while you are sleeping. Could talk about adenosine. Process C on the other hand fluctuates throughout the day. During the daytime, we see a very low likelihood of falling asleep. Increased likelihood of falling asleep in the evening. Really the difference between the two factors influence the likelihood to fall asleep. Sleep propensity is a function of both homeostatic sleep need and the circadian rhythm. Rhythm throughout the day

Measuring sleepiness objectively: The Multiple Sleep Latencies Test (MSLT)

Need to bring a patient into the clinic. Measures sleep latency over repeated sleep onset periods. Participant/patient asked to refrain from caffeine or alcohol. Could impact ability to fall asleep. Awoken after 2 hours. Allowed to fall asleep again. See how long it takes to fall asleep each time. Procedure repeated 4-5 times. Polysomnogram used to gauge time of sleep onset. Daytime sleep latencies <5 mins indicative of pathology or sleep deprivation

Look at the activity of a group of six pyramidal neurons in the cerebral cortex

Neural activity that tends not be to synchronized produces many small peaks in the EEG. Firing in a way that is not synchronized. Small peaks varying in time and small amplitude. Neural activity that is more synchronized will produce fewer peaks, but they are larger. Cortex exhibiting synchronized activity. Higher amplitude, larger but slower peaks. Whenever we see slower activity in an EEG, going to see larger peaks. More neurons are being synchronously activated. The switch/transition from synchronized activity to a more desynchronized state of neural brain activity is indicated of switching to a different phase of sleep. Characterizes different stages of sleep

Sleep promoting factors cont.

Nitric oxide (NO): small gaseous molecule, diffuses across cell membrane. Highest levels during waking, rise quickly with sleep deprivation. Found in wake-promoting cholinergic regions of brainstem. Triggers adenosine release. Found throughout nervous system. Interleukin-1: small signaling peptide used by immune system. Synthesized in brain by glia, elsewhere by immune cells. Level rises during waking, peak just before sleep. Direct administration induces fatigue and sleepiness. Affect how prone we are to fall asleep

Thalamic rhythmicity during waking and sleeping

Non-REM sleep versus the waking state. Looking at signaling in the thalamus during waking and sleeping. During non-REM sleep, the thalamus goes into burst mode firing. When thalamus in burst mode firing, will fire a burst of action potentials. Then, enter a period of hyperpolarization where there is no firing or action potentials. As a consequence, sensory info cannot be conveyed to the cortex. In the awake state, under the influence of excitatory neurotransmitters (like acetylcholine, noradrenaline, and serotonin), these neurons in the thalamus enter a tonic mode of firing. When in tonic mode, do not have periods of hyperpolarization. Information can be conveyed to the cortex

How much sleep do we need?

Normal sleep needs highly variable between adults. Tremendous amount of individual variation. Range is about 5-10 hours. Average is 7.5 hours. Commonly 6.5-8.5 hours. Best measure of sleep requirements is degree of refreshment. What is the quality of your energy level in your waking hours

Oscillatory circuitry using only two neurons

Notion of circuitry that only involves two neurons. One excitatory neuron and one inhibitory. See alternation of activity between these two. Periods of time where excitatory neuron is firing and stimulating inhibitory interneuron. Keeps stimulating until the inhibitory starts firing to inhibit the excitatory. Alternation for periods of activity

Functions of brain rhythms

Very important for sleep and waking. Many possible roles have been proposed for brain rhythms. Little definitive evidence for their roles. In some stages of sleep: "disconnect" cortex from sensory inputs by creating slow variations in excitability and periods of time when the cortex cannot receive sensory input (from burst firing in thalamus). Rhythmic firing prevents detailed sensory info from reaching cortex. When afferent information enters the thalamus, can either send info to cortex or it can be inhibited. One theoretical potential circuit. Gamma in wakefulness: oscillatory; synchronize activity in brain regions that are working together (like for example, different parts of the visual field that must work together when analyzing an object). Similar periods of increased or decreased likelihood of firing. Alpha in wakefulness: "idling" state of unstimulated cortex or cortical regions corresponding to unattended stimuli. When choosing to ignore a stimulus. Looking at something more specifically and ignoring other. That part of the brain will exhibit more alpha to inhibit

History of EEG recordings

Was performed directly on the surface of the brain for animals in 19th century. Hans Berger is the founder of EEG use and study in humans. Something meaningful, told you something useful about brain function. Took almost his entire career to demonstrate. Making recordings of his children's brains. Technology for studying brain function. Changed in its characteristics during sleep. Different around tumors. Around time it was accepted as being indicative of brain function (not first created), 1970 EEG was the dominant technology used by neurologists. It was really the only thing available to provide some objective measurement of brain function in the living brain. CT scans discovered right after

Neural mechanisms for oscillatory brain rhythms

Why do we see rhythms and synchronization between different neurons? A central clock (pacemaker): rhythm is generated and imposed by another brain region. Population of neurons acting like a pacemaker. Generating rhythm that can be pushed to other neurons using synaptic connections. Periods of time of increased excitability and reduced excitability. Another possibility: mutual excitation or inhibition: rhythm results from neural circuitry that uses feedback to covert continuous excitatory input into oscillatory activity. Population of neurons can be interconnected in a circuit that produces this oscillatory activity. Using feedback to turn a continuous excitatory input into oscillatory activity

The history of sleep science (and sleep medicine)

William Dement. Father of sleep medicine. Began studying sleep science and application in the 1950s. Little scientific understanding of sleep at the time. 1953: discovered rapid eye movement (REM) and revealed its importance for dreaming. Most memorable and most vivid dreams. Discovered the phases of the sleep cycle. 90-minute cycle. Revealed links between sleep deprivation and hazards like car crashes and adverse health conditions. Important consequences of sleep deprivation. Speculated that ~20% of population suffered from sleep deprivation. Underneath our current estimates, whether that reflects the time and history or he just misestimated the rate of sleep deprivation. Founded the first sleep lab in America. Founded the American Sleep Disorders Association: American Academy of Sleep Medicine. Still just in the growth period of learning about sleep, so much to learn

Subjective measures of sleepiness cont.

Epworth Sleepiness Scale. More fine grain. Often used to screen patients to find out if they should actually go have a sleep study or not. How likely to fall asleep when engaging in a certain activity

Sleep-promoting factors cont.

Melatonin: released into bloodstream by pineal gland. Back of midbrain kinda. Release inhibited by bright light. Level rises in evening, peaks in early morning, falls to baseline around time of rising. Affects of bright light on melatoning. Why should not be using bright devices before bed. Questionable value as a sleep aid