1. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Neuroscience: Exploring the Brain, 3e Chapter 19: Brain Rhythms and Sleep

2. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Introduction Rhythmic Activities –Sleeping and waking, hibernation, breathing, walking… –Cerebral cortex: Range of electrical rhythms depending on state of consciousness –EEG: Classical method of recording brain rhythms from cerebral cortex –Circadian rhythms: Change in physiological functions according to brain clock

3. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Electroencephalogram The Electroencephalogram (EEG) –Measurement of generalized cortical activity –Noninvasive, painless –Diagnose neurological conditions such as epilepsy, sleep disorders, research

4. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Recording Brain Waves –Electrodes to scalp, low-resistance connection –Connected to banks of amplifiers and recording devices –Voltage fluctuations measured (tens of microvolts) –Electrode pairs: Measure different brain regions –Set of simultaneous squiggles, voltage changes between electrode pairs The Electroencephalogram

5. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins EEG records very small electrical fields generated by synaptic currents in pyramidal cells The Electroencephalogram

6. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Generating Large EEG Signals by Synchronous Activity The Electroencephalogram

7. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Magnetoencephalography (MEG) –Recording miniscule magnetic signals generated by neural activity Comparison with EEG, fMRI, PET MEG localizes sources of neural activity better than EEG MEG cannot provide detailed images of fMRI EEG, MEG  measure neuron activity, fMRI, PET  changes in blood flow, metabolism The Electroencephalogram

8. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins EEG Rhythms –Categorization of rhythms based on frequency Beta: Greater than 14 Hz, activated cortex Alpha: 8-13 Hz, quiet, waking state Theta: 4-7 Hz, some sleep states Delta: Less than 4 Hz, deep sleep –Deep Sleep High synchrony, high EEG amplitude The Electroencephalogram

9. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins A Normal EEG The Electroencephalogram

10. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Seizures and Epilepsy –Epilepsy: Repeated seizures –Causes: Tumor, trauma, infection, vascular disease, many cases unknown –Generalized: Entire cerebral cortex, complete behavior disruption, consciousness loss –Partial: Circumscribed cortex area, abnormal sensation or aura –‘Absence’ (childhood)epilepsy : Less than 30 sec of generalized, 3 Hz EEG waves- no seizures The Electroencephalogram

11. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Generalized Epileptic Seizure The Electroencephalogram

12. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Sleep –Universal among higher vertebrates –Sleep deprivation, devastating –One-third of lives in sleep state –Defined: “Sleep is a readily reversible state of reduced responsiveness to, and interaction with, the environment.” Sleep

13. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Three Functional Brain States Sleep

14. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Physiological changes during non-REM and REM sleep Sleep Non-REM: Slow-wave (EEG< 4Hz (Δ)) sleep REM: Fast-wave (EEG > 14Hz (β)) sleep EEG pattern similar to awake states (α, β) Start of REM cycle: activity of cholinergic neurons REM cycle end: Activity of 5HT and NE neurons

15. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins EEG Rhythms During Sleep Sleep

16. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Why Do We Sleep? –Recovery time for brain? –Restoration? Sleep to rest and recover, and prepare to be awake again –Adaptation? Sleep to keep out of trouble, hide from predators Sleep

17. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Functions of Dreaming and REM Sleep –Body requires REM sleep –Sigmund Freud: Dream functions- Wish- fulfillment, conquer anxieties –Allan Hobson and Robert McCarley: Activation- synthesis hypothesis –Avi Karni: Certain memories require strengthening period  REM sleep Sleep

18. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Neural Mechanisms of Sleep –Critical neurons  Diffuse modulatory neurotransmitter systems –Noradrenergic and serotonergic neurons: Fire during and enhance waking state; active at end of REM cycle –Cholinergic neurons: enhance REM events; active during waking; may initiate REM cycles –Diffuse modulatory system control rhythmic behaviors of thalamus  controls cortical EEG  sensory input flow to cortex blocked by slowed thalamic rhythms –Activity in descending branches of diffuse modulatory systems (e.g., inhibit motor neurons) Sleep

19. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Wakefulness and the Ascending Reticular Activating System –Giuseppe Moruzzi: Lesions in midline structure (reticular ‘activating’ system) of brainstem: State similar to non-REM sleep Lesions in lateral tegmentum: Does not cause non-REM state sleep Electrical stimulation of midline tegmentum of midbrain: Cortex moved from slow, rhythmic EEGs of non-REM sleep to alert and aroused state Sleep

20. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Falling Asleep and Non-REM State –Sleep: Progression of changes ending in non-REM state –Non-REM sleep: Decrease in firing rates of most brain stem modulatory neurons using NE, 5-HT, ACh –Stages of non-REM sleep: EEG sleep spindles Spindles disappear Replaced by slow, delta rhythms (less than 4 Hz) Sleep

21. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins PET Images of Waking and Sleeping Brain Control of REM Sleep by Brain Stem Neurons Sleep

22. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Sleep-Promoting Factors –Muramyl dipeptide: isolated from the CSF of sleep- deprived goats, facilitates non-REM sleep –Interleukin-1: Synthesized in brain (glia, macrophages), stimulates immune system –Adenosine: Sleep promoting factor; released by neurons; may have inhibitory effects of diffuse modulatory systems –Melatonin: Produced by pineal gland, released at night-inhibited during the day (circadian regulation); initiates and maintain sleep; treat symptoms of jet lag and insomnia Sleep

23. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Gene Expression During Sleeping and Waking –Cirelli and Tononi: Comparison of gene expression in brains of awake and sleeping rats –0.5% of genes showed differences of expression levels in two states –Increased in awake rats Intermediate early genes Mitochondrial genes –Increased in sleeping rats: protein synthesis- and plasticity-related genes –Changes specific to brain not other tissues Sleep

24. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Circadian rhythms circa = approximately; dies = a day Daily cycles of light and dark –Schedules of circadian rhythms vary among species –Physiological and biochemical processes in body: Rise and fall with daily rhythms –Daylight and darkness cycles removed, circadian rhythms continue –Brain clocks Circadian Rhythms

25. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Circadian rhythms and physiological functions Circadian Rhythms

26. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Biological Clocks (cont’d) –Free-run: Mammals completely deprived of zeitgebers, settle into rhythm of activity and rest, but drifts out of phase with 12 hr day/light cycle Components of biological clock Light-sensitive input pathway  Clock  Output pathway Circadian Rhythms

27. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Circadian rhythms of sleep and wakefulness Circadian Rhythms

28. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins The Suprachiasmatic Nucleus: A Brain Clock –Intact SCN produces rhythmic message: SCN cell firing rate varies with circadian rhythm –Each SCN cell is a small clock –TTX does not disrupt their rhythmicity Suggests that action potentials don’t play a role Circadian Rhythms

29. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins A New Type of Photoreceptor –Berson and colleagues: Discovered specialized type of ganglion cell in retina Photoreceptor, but not rod or cone cell Contains melanopsin, slowly excited by light Synapses directly onto SCN neurons –SCN output axons: Parts of the hypothalamus, midbrain, diencephalons, use GABA as primary neurotransmitter, lesions disrupt circadian rhythms Circadian Rhythms

30. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins SCN Mechanisms (Cont’d) –Molecular Clocks similar in humans, mice, flies, mold –Clock genes: Period (Per), Timeless (Tim), Clock –Takahashi: Regulation of transcription and translation, negative feedback loop Circadian Rhythms

31. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Concluding Remarks Rhythms –Ubiquitous in the mammalian CNS –Intrinsic brain mechanisms –Environmental factors –Interaction of neural processes and zeitgebers (like SCN clock) –Function of rhythms Unknown but arise mainly as a secondary consequence -Sleep research Little known about why we sleep and the function of dreams and sleep

32. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins End of Presentation

33. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanisms of Synchronous Rhythms –Rhythms can be led by a pacemaker. or arise from collective behavior of all participants The Electroencephalogram

34. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanisms and Meanings of Brain Rhythms –Synchronized oscillation mechanisms Central clock/Pacemaker Collective methods (“jam session”) –Thalamus  massive cortical input  influence cortex Neuronal oscillations Voltage-gated ion channels The Electroencephalogram

35. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Functions of Brain Rhythms –Hypotheses Brain’s way of disconnecting cortex from sensory input No direct function, by-products of strongly interconnected circuits Walter Freeman –Neural rhythms coordinate activity, synchronize oscillations, bind together The Electroencephalogram

36. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Biological Clocks –Jacques d'Ortous de Mairan Mimosa plant Leaf movement continues on ‘schedule’ in the dark  sensing sun movement –Augustin de Candolle Plant responded to internal biological clock –Zeitgebers (German for “time-givers”) Environmental time cues For mammals: Primarily light-dark cycle Circadian Rhythms