Sleep Slides available at: Tony Gardner-Medwin, Physiology room 331

n Clinical Problems n Characteristics n Changes in CNS n Deprivation n Control n Good textbook: Kandel & Schwartz – Principles of Neural Science n [ But they nearly all are adequate ] SUMMARY

1.Sleep is not 1 state, but 2 radically different states 2.The brain is not resting, but is active (in altered ways) 3.The brain is (arguably) conscious, but very poor at remembering what it was experiencing. Three conclusions :

INSOMNIA & poor sleep Problems with waking tasks Psychological/ Psychiatric problems Sleep apnoea Shiftwork, jetlag NARCOLEPSY (sudden daytime sleepiness) & CATAPLEXY (sudden paralysis) HYPERSOMNIA (night & day) Principal Clinical Problems associated with sleep Risk of Death Sleep asthma ?? Some cot deaths? ??

Electroencephalogram (EEG) Invasive recording of ‘field potentials’ summed from many cells Single cell recording in unanaesthetised animals (extracellular) Lesions Stimulation Pharmacological intervention Psychophysics (sensory performance) PET, MRI yet to have much impact C C EOG Frontal Parietal Occipital EEG Techniques for studying the sleeping brain

SWS

Slow Wave Sleep REM/Paradoxical Sleep EEG Large AmplitudeLow Amplitude (cf waking) Slow Waves ~ 1 Hz(but theta rhythm in hippocampus) MUSCLESReduced toneTotal relaxation (e.g. in postural & neck muscles) SPINAL Some reductionStrong descending inhibition REFLEXESof motoneurons AROUSALto ‘significant’ stimuliRaised threshold (deep sleep) but often waking from REM PHASICMuscle twitchesSudden eye movements (REM) EVENTSSudden CNS discharges REPORTS‘dreams’ 0-50%‘dreams’ 80%-90% ON WAKING& ‘thinking’

Slow Wave Sleep REM/Paradoxical Sleep ……ctd…. REPORTS‘dreams’ 0-50%‘dreams’ 80%-90% ON WAKING& ‘thinking’ - but NB poor recall unless immediately after rapid arousal % of SLEEP60% - 85%~40% infants ~20% most of life ~15% old age WHENInitially and in cyclesNot initially (except narcoleptics) ~ 90 min cycle

1.Altered neuronal firing patterns & increased synchrony Changes in CNS Activity

AWAKE SWS REM Single pyramidal tract neuron activity in monkey motor cortex

1.Altered neuronal firing patterns & increased synchrony 2.Cutting off sensory inflow, e.g. at LGN Changes in CNS Activity

SWS Awake Responses from cat LGN (lateral geniculate nucleus) to 0.1 Hz visual stimulation. Brainstem sectioned.

1.Altered neuronal firing patterns & increased synchrony 2.Cutting off sensory inflow, e.g. at LGN 3.Cutting off motor outflow by descending inhibition (NB brainstem lesions and 5HT (serotonin) depleters can prevent this) 4.Different “connectivity” of brain, e.g. “PGO” waves (Pons – Geniculate – Occiptal cortex) - visual cortex gets signals from the brainstem instead of from the eyes during REM sleep Changes in CNS Activity

Activity in cat optic radiation (LGN projection to visual cortex). Awake and in paradoxical (REM) sleep

Visual cortex Optic chiasma Optic radiation LGN

1. Decreased sleep latency 2. Microsleep episodes (& can be EEG slow waves) 3. Poor performance in long boring tasks (?=2) but short term performance usually normal 4. Irritability, bizarre statements, paranoia (? ~ cf. schizophrenia) 5.Increased % of SWS on recovery night (though only <~30% of lost sleep is recovered) 6.In animals can -> death after ~ 2 weeks, associated with metabolic and immune abnormalities. Effects of Total Sleep Deprivation Effects of REM Deprivation above, similar to total sleep deprivation Becomes difficult to arouse or shift from REM (5) is opposite: Increased REM on recovery night, and decreased latency to REM Possible improvement of affect in endogenous depression and bipolar disorder

Nuclei of certain known chemical neuro-modulatory systems AcetylCholine: Tegmentum [PGO] Noradrenaline: Locus Coeruleus [Arousal] 5HT (serotonin): Raphe [Arousal, SWS] Arousal and Neuro-modulatory Systems Thalamus Diffuse projection from RETICULAR ACTIVATING SYSTEM (R.A.S.) -> arousal ‘Specific’ sensory signals to thalamus and cortex ‘Non-specific’ collaterals of sensory axons go to RETICULAR ACTIVATING SYSTEM (R.A.S.)

Sleep Please use the Web Discussion Forum for problems/queries Tony Gardner-Medwin, Physiology room 331