Rhythms of the Brain 1 of 8

Rhythms of the Brain 1 of 8 I. EEG A. Measures current flow during synaptic excitation of the dendrites of a large number of pyramidal cells. 1. 80% of the brain made up of these cells 2. thousands of these cells must fire together to make an EEG signal big enough to see B. Amplitude of the EEG depends upon the synchrony of the cells timing plays the biggest role in the amplitude of EEG wave. C. Rhythms 1. beta (14 Hz) is the fastest with the smallest amplitude 2. alpha (8-13 Hz) associated with relaxed, waking state 3. theta (4-7 Hz) occurs during some sleep 4. delta (less than 4 Hz) is large in amplitude and associated with deep sleep D. Mechanisms and Meanings of Brain Rhythms 1. The generation of synchronous signals a) Synchronization occurs in two ways (1) Pacemaker guides the activity of a large number of neurons (2) Neurons share or distribute timing among themselves by exciting and inhibiting one another (collective method) b) Rhythmic activity in mammalian brain uses both methods (1) Oscillations of the pacemaker cells in the thalamus due to voltage-gated ion channels that allow rhythmic self-sustaining discharges even when there is no input to the cell (a) Thalamic cells synchronized with each other through the collective method (b) These rhythms are transmitted to the brain through the thalamocortical axons 2. Functions of brain rhythms a) No one really knows but there are three ideas (1) Rhythms of the thalamus inhibit or block organized sensory info from reaching the brain during sleep (but why not just shut the thalamus off?) (2) Synchrony binds various areas of the brain that are working simultaneously so that you have a single perceptual experience (3) No direct function but an interesting by-product of neural activity E. Epilepsy 1. generalized seizures: entire cerebral cortex 2. partial seizures: circumscribed areas of the cortex 3. due to extensive feedback circuitry, the cortex is always on the verge of runaway excitiation 4. epilepsy isn t a disease per say but is the symptom of disease

Rhythms of the Brain 2 of 8 a) tumors b) trauma c) metabolic dysfunction d) infection e) vascular disase f) many mechanisms g) may be genetic causes too 5. can result from changes in excitation or inhibition in the brain a) GABA antagonists promote seizures b) Anticonvulsants (1) Prolong the inhibitory actions of GABA (2) Decrease the firing rates of certain neurons 6. Types of seizures a) Generalized b) Partial (1) Absence seizures show very little or no convulsive activity but more like a loss of consciousness. (2) Seizures that start in sensory areas are accompanied by auras (3) Partial seizures can spread and paying attention to where the seizures originate can reveal where the problem is (a) John Hughlings Jackson mapped the somatotopic in this way II. SLEEP A. Intro 1. We spend 1/3 of our lives asleep and about ¼ of that is spent dreaming 2. sleep: a readily reversible state of reduced responsiveness of and interaction with the environment 3. sleep is a universal in mammals and maybe all animals a) can be fatal in animals b) can be fatal in humans (1) fatal familial insomnia caused by rare genetic disorder; it destroys the pacing cells of the thalamus that help turn on sleep B. functional states of the brain 1. REM sleep: awake-like state of the brain during sleep that is accompanied by vivid dreams a) Active, hallucinating brain in a paralyzed body b) Detailed dreams of a bizarre nature c) Looks like an active, awake brain d) Oxygen consumption higher than when awake and working complex math problems e) Sympathetic activity is increased (1) Downward drift of temperature from lose of core controls (2) Irregular heart rate and respiration (3) Engorgement of the genitals regardless of the content of the dreams 2. non-rem sleep: resting state of the brain in which complex dreams are not generated a) seems to be designed for rest b) muscle tension is reduced (1) body capable of movement but the brain doesn t signal for it c) temperature and energy consumption lowered d) increased parasympathetic activity e) neurons oscillate in high synchrony (1) most sensory information is not reaching the cortex f) idle brain but immovable body

Rhythms of the Brain 3 of 8 3. summary BEHAVIOR AWAKE NON-REM SLEEP REM SLEEP EEG Low voltage, fast High voltage, slow Low voltage, fast Sensation Vivid, externally generated Dull or absent Vivid, internally generated Thought Logical, progressive Logical, repetitive Vivid, illogical, bizarre Movement Continuous, voluntary Occassional, involuntary Muscle paralysis; movement commanded by the brain but not carried out Rapid eye movement Often Rare often C. The Sleep Cycle 1. 75% of sleep is non-rem; 25% is REM 2. Move through distinct stages of sleep; about every 90 minutes we complete a cycle a) Shorter rhythms like these within sleep are known as ultradian cycles 3. The stages a) stage 1 b) stage 2 (1) sleep spindles from thalamic pacing cells (2) K complexes c) Stage 3 d) Stage 4 e) Ascend back up but the transition from stage 2 to stage 1 is actually the move into REM 4. more time in deep sleep early in the night and then more time in REM toward morning. Still a 30 minute refractory period between REM stages. 5. How much sleep do you need? a) Ranges from 5 to 10 hours per night b) 6.5 to 8.5 for young adults c) best measure is quality of time the next day D. Why do we sleep? 1. only mammals and some birds have a REM phase a) bottlenose dolphins sleep half a brain at a time; no REM sleep b) Indus dolphins microsleep in snatches of 4 6 seconds at a time but that will be 7 hours per day. 2. Two categories of theories about why we sleep a) Restoration theories: something being repaired or restored in the body (1) No process has been identified (2) No substance has been identified

Rhythms of the Brain 4 of 8 (3) No toxin has been identified (4) However research on animals and humans does seem to support the idea that something is being restored and it is related to brain function, not body function b) Adaptation theories: stay safe and conserve energy when you can t normally function E. Functions of dreaming and REM sleep 1. dreaming occurs in REM and non-rem sleep 2. REM sleep is peculiar in comparison to non-rem sleep 3. REM rebound shows that there is a need for REM sleep a) No psychological harm found from REM deprivation b) REM does not equal dreaming so dreaming might not be the important component 4. Freud s theory a) Dreams are symbolic manifestation of unconscious wishes or desires b) Dreams may help us to conquer anxiety provoking events 5. Hobson and McCarley s activation-synthesis theory a) Dreams result from random activity in the pons being carried to the cortex by the thalamus b) Pontine neurons activate areas of the cortex that elicit emotions and memories c) The cortex attempts to synthesize these things into something meaningful d) This theory explains the weirdness of dreams but does not account for the fluid and meaningful dreams that we sometimes have 6. REM and dreaming might play an important role in memory integration or consolidation a) Depriving humans or rats of REM sleep impairs the ability to learn new tasks b) There might be an increase in REM sleep following the learning of something difficult 7. No scientific evidence of sleep learning; in fact sleep is a very amnesic state F. Neural Mechanisms of Sleep 1. General characteristics a) Sensory afferents are not necessary for the sleep wake cycle b) Sleep requires the participation of several brain areas (1) It is controlled by cells deep in the brain (2) Principles of the control system (a) Diffuse modulatory system most critical in controlling sleep (b) NE and 5-HT systems most involved in wakefulness (c) Some ACh neurons enhance REM events; other ACh neurons are involved in waking (d) Diffuse modulatory system controls the rhythms of the thalamus which controls the rhythms of the cortex; sleep related rhythms seem to block sensory input to the cortex (e) Sleep also involves descending branches of the diffuse modulatory system including the blocking of spinal motor neurons 2. Wakefulness, falling asleep, and non-rem sleep a) Fire more before waking (1) Locus coeruleus (2) Raphe nucleus (3) ACh neurons of the brainstem and basal forebrain (4) Histamine neurons of the midbrain b) Fire more during sleeping (1) Lowered diffuse modulatory system activity (2) A subset of basal forebrain neurons become active before sleep and silent during wakefulness.

Rhythms of the Brain 5 of 8 3. Mechanisms of REM sleep a) REM (1) Visual cortex about equally active during REM and non-rem sleep (2) Increased extrastriate cortical activity (a) Not dependent upon visual cortex activity (3) Increased limbic activity (4) Decreased frontal lobe activity b) Non-REM (1) Visual cortex about equally active during REM and non-rem sleep although it appears to be a bit less active (2) Decreased limbic activity (3) Increased frontal activity c) Control of REM (1) Locus coeruleus activity decreased (2) Raphe nucleus activity decreased (3) ACh neurons in the pons increase activity and seem to initiate dreaming (4) Inhibition of the spinal motor neurons (a) REM sleep disorder is acting out dreams and is caused by disruption of the brainstem mechanisms that lead to atonia (5) Narcolepsy seems to be related to REM control mechanisms (a) Excessive daytime sleepiness (b) Cataplexy: sudden muscular paralysis that is maintained during consciousness (c) Sleep paralysis: loss of muscle control during the transition between sleeping and waking (d) Hypnagogic hallucinations: graphic dreams that are often very frightening that accompany sleep onset and may follow sleep paralysis (e) Narcoleptics go directly from waking to REM sleep without the long periods of non-rem sleep that usually comes first. It seems to be an intrusion of REM characteristics into waking states. Watch the Sleeping Brain video

Rhythms of the Brain 6 of 8 Summary of Cellular Mechanisms of Sleep and Wakefulness (taken from Purves, et. al 1997, pg 509) Brainstem nuclei responsible Neurotransmitter involved Activity state of the relevant brainstem neurons Wakefulness Cholinergic nuclei of ponsmidbrain ACh Active junction Locus coeruleus NE Active Raphe nuclei 5-HT Active Non-REM sleep Cholinergic nuclei of ponsmidbrain ACh Inactive junction Locus coeruleus NE Inactive Raphe nuclei 5-HT Inactive REM sleep on Cholinergic nuclei of ponsmidbrain ACh Active (PGO waves) junction Raphe nuclei 5-HT Inactive REM sleep off Locus coeruleus NE Active 4. Sleep promoting factors a) Muramyl dipeptide: a produce of bacteria cells walls (1) Somehow increased following sleep deprivation (2) Associated with the immune system (3) May be released by bacteria in the intestines b) Interleukin-1 is synthesized by the glia and in macrophages; it stimulates the immune system and may promote sleep c) Adenosine is a neuromodulator that works throughout the brain (1) Caffeine and other substances used to keep people awake are adenosine agonists (2) Has an inhibitory effect on the diffuse modulatory system for ACh, NE, and 5-HT (3) Activity of the awake brain increases adenosine levels (4) This increasing suppression of these modulatory systems gradually leads to a brain that begins to fall into synchronized activity and enters sleep. (5) After sleep starts, adenosine levels slowly begin to fall which allows the activating systems to return to activity and to awake the brain. (6) High levels of adenosine might be a cue that the brain needs rest (a) Possible that glycogen depletion in the astrocytes might increase adenosine release setting up a negative feedback loop 5. Gene expression during sleeping and waking a) The behavioral states of sleeping and waking are different at the molecular level b) Cerebral cortex shows more protein synthesis c) camp levels are lower during sleeping d) expression of genes differs

Rhythms of the Brain 7 of 8 (1) low expression of genes that code for transcription factors that affect the expression of other genes (a) may be related to a lack of learning and memory formation during this state (2) low expression of mitochondrial genes (a) may be related to lower metabolic demands during sleep III. CIRCADIAN RHYTHMS A. Intro 1. fluctuations of various behaviors over an approximately 24 hour cycle 2. does not completely require exposure to light and dark a) exposure to light and dark helps to entrain the cycles B. Biological clocks 1. environmental time cues are called zeitgebers a) light-dark cycle b) availability of food and water c) social contact d) environmental temperature cycles e) cycles of noise and quiet 2. when allowed to free run the cycle makes some changes a) first settles into roughly 25 hour period b) then moves to 30-36 hours with about 20 hours awake and 12 hours asleep c) behavior and physiology do not always cycle together (1) body temp and some other physiological measures stay on a 24 hour cycle (2) this means our behavior and physiological cycles can get out of wack and make things difficult for us (3) an implication is that we have more than one biological clock (4) the best way to resychronize our cycles is to expose ourselves to bright lights. C. The suprachiasmatic nucleus: a brain clock 1. a brain clock requires light sensor fi clock fioutput pathway 2. light helps keep the biological clock entrained but isn t necessary for its running 3. the suprachiasmatic nucleus serves as the biological clock in mammals a) lesions in the SCN do not abolish sleep (1) some debate about its effects your book claims that animals continue to sleep according to the light-dark cycle (2) Purves text claims that destruction of the SCN destroys the circadian rhythm but not the amount of REM and non-rem sleep they occur at random intervals b) The photosensitive mechanism in the retina that controls the SCN via the retinohypothalamic tract has not yet been identified but it is not the rods or cones. The primary candidate is a retinal protein called crypotchrome c) SCN probably works primarily by inhibiting areas of the hypothalamus and midbrain to which is connected D. SCN mechanisms

Rhythms of the Brain 8 of 8 1. isolated SCN neurons still change their firing rates, glucose usage, ADH production, and protein synthesis on a 24 hour cycle 2. SCN cells send signals through action potentials but these action potentials are not necessary for their circadian rhythms as shown by blocking the firing with TTX SCN cells still remain rhythmic 3. clocks dependent upon genes a) clock gene transcribed to make mrna b) new proteins send feedback that inhibits transcription decreasing gene expression c) protein levels fall and gene transcription starts again 4. synchrony of SCN neurons not dependent upon action potentials possibly a chemical, electrical, or glial signal allows the synchrony