Neuroscience Exploring the Brain 3 e Chapter 19

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 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Electroencephalogram • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Electroencephalogram • EEG records very small electrical fields generated by synaptic currents in

The Electroencephalogram • Generating Large EEG Signals by Synchronous Activity Copyright © 2007 Wolters

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

The Electroencephalogram • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Electroencephalogram • A Normal EEG Copyright © 2007 Wolters Kluwer Health | Lippincott

The Electroencephalogram • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Electroencephalogram • Generalized Epileptic Seizure Copyright © 2007 Wolters Kluwer Health | Lippincott

Sleep • 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. ” Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sleep • Three Functional Brain States Copyright © 2007 Wolters Kluwer Health | Lippincott

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

Sleep • EEG Rhythms During Sleep Copyright © 2007 Wolters Kluwer Health | Lippincott

Sleep • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sleep • Functions of Dreaming and REM Sleep – Body requires REM sleep – Sigmund Freud: Dream functions- Wishfulfillment, conquer anxieties – Allan Hobson and Robert Mc. Carley: Activationsynthesis hypothesis – Avi Karni: Certain memories require strengthening period REM sleep Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sleep • 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) Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sleep • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sleep • 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) Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sleep • PET Images of Waking and Sleeping Brain • Control of REM Sleep by Brain Stem Neurons • Narcolepsy: Insights into REMHypocretin defic, receptor mutation, KO mice Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Narcolepsy, cataplexy: receptor mutation Hypocretin deficiency, Copyright © 2007 Wolters Kluwer Health | Lippincott

Narcolepsy, mice: Knock-out of gene for Hypocretin precursor peptide Copyright © 2007 Wolters Kluwer

Sleep (slow-wave) • Sleep-Promoting Factors – Muramyl dipeptide: isolated from the CSF of sleepdeprived 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 on 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Sleep • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Circadian Rhythms 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Circadian Rhythms Circadian rhythms and physiological functions Copyright © 2007 Wolters Kluwer Health |

Circadian Rhythms • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Circadian Rhythms Circadian rhythms of sleep and wakefulness Copyright © 2007 Wolters Kluwer Health

Circadian Rhythms • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Circadian Rhythms • 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, diencephalon, use GABA as primary neurotransmitter, lesions disrupt circadian rhythms Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Circadian Rhythms • 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 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

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

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

The Electroencephalogram • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Electroencephalogram • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Circadian Rhythms • 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 Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins