PSYC 460 -- Notes on Sleep (Part II) -- Dr. King

Slide 1: Physiology of Sleep

Slide 2: Sleep is Regulated 
I. We make up for losses. 
II. SWS is made up before REM. 
III. We deduct daytime sleeping from nighttime sleeping. 

Slide 3: Chemical Control of Sleep 
I. Is there a circulating chemical produced during wakefulness that promotes
   sleep? 
   A. If so, it is not in the general circulation. 
   B. Some marine mammals sleep one brain hemisphere at a time. 
   C. Animals with shared circulatory systems sleep independently. 

Slide 4: Chemical Control of Sleep 
I. If there is a sleep-promoting substance, it must be restricted to the brain. 
   A. Adenosine is a prime candidate. 
   B. It is produced in areas of the brain that consume energy very rapidly. 
   C. Adenosine may promote delta activity in the EEG. 
   D. Adenosine antagonists (e.g., caffeine) promote wakefulness. 

Slide 5: Neural Control of Arousal 
I. the reticular formation and ascending reticular activating system (ARAS) 
II. part of the reticular formation (RF)

Slide 6: Neural Control of Arousal
I. Moruzzi & Magoun (1949) found that electrical stimulation of the pontine RF
   causes alerting, and sleeping cats wake up. 
II. Lindsley, et al. (1950) found that midbrain lesions that interrupt only 
    ascending RF impulses, leaving the sensory pathways in tact, cause 
    continuous SWS. 

Slide 7: The RF - Acetylcholine
I. drugs affecting ACh 
   A. agonists - increase cortical EEG signs of arousal 
   B. antagonists - have the opposite effect 
II. There are two groups of ACh neurons that produce cortical arousal and EEG
    desynchrony when electrically stimulated. 
   A. dorsal pontine RF - stimulation here increases cortical ACh release by
      350% 
   B. basal forebrain - anesthetizing these cells eliminates the effect of
      pontine stimulation 
 
Slide 8: The RF - Acetylcholine 
I. During SWS, ACh activity in the cortex is substantially reduced. 
II. During REM sleep and quiet waking, ACh activity is increased. 
III. When an animal is aroused, microdialysis shows increased release of ACh
     in several brain areas including the cortex.  ACh activity is at its
     highest during aroused waking. 

Slide 9: The RF - Norepinephrine 
I. "Pep pills" (such as amphetamine) are NE agonists.  They produce arousal
   and sleeplessness. 
II. This drug effect is mediated by the locus coeruleus in the pontine RF. 
III. Activity in the locus coeruleus of unrestrained rats exhibits a close
     relationship to behavioral arousal. 
IV. The highest activity occurs during behavioral vigilance. 

Slide 11: The RF - Serotonin 
I. Stimulation of the raphe nuclei of the pontine and medullary RF produce
   behavioral and cortical arousal. 
II. PCPA, a serotonin biosynthesis inhibitor, reduces cortical arousal (but
    also produces profound insomnia). 
III. Activity of neurons in the dorsal raphe nucleus is correlated with the
     behavioral activity cycle. 

Slide 13: The RF - Histamine 
I. Cell bodies for this neurotransmitter are found in the tuberomammilary
   nucleus of the hypothalamus. 
II. Axons project to the cortex, thalamus, basal ganglia, hypothalamus, and...
III. ...to the ACh neurons of the forebrain. 
IV. Histamine produces arousal directly by acting on the cortex, and
    indirectly by acting on the basal forebrain ACh system. 
V. Antihistamines that cross the BBB and block H1 receptors in the brain
   cause drowsiness. 

Slide 14: The RF - Orexin/Hypocretin 
I. Orexin (hypocretin) neurons originate in the lateral hypothalamus and
   terminate in the locus coeruleus, raphe nuclei, tuberomammillary nuc.,
   and on the ACh neurons in the pons and in the basal forebrain. 
II. These neurons are active during wakefulness and inactive during sleep. 

Slide 16: Summary 
I. five systems of arousal neurons 
   A. acetylcholine - dorsal pons and basal forebrain 
   B. norepinephrine - locus coeruleus 
   C. serotonin - raphe nuclei of the pons and medulla 
   D. histamine - tuberomammilary nucleus of the hypothalamus 
   E. orexin - lateral hypothalamus 
II. a high level of activity in these neurons keeps us awake, while a low
    level puts us to sleep 
III. but what controls the activity of these arousal neurons? 

Slide 17: Neural Control of SWS 
I. ventrolateral preoptic area - a nucleus in the hypothalamus that uses
   primarily GABA as its neurotransmitter (and a second inhibitory
   neurotransmitter called galanin, a peptide) 
II. these seem to be the primary "sleep neurons"
III. they are active during SWS and quiet during waking 
IV. they send inhibitory impulses to each of the five arousal systems 
V. in turn, they receive inhibitory impulses particularly from the ACh and
   NE arousal systems 

Slide 19: Neural Control of SWS 
I. the sleep-waking flip-flop 
   A. a flip-flop is an oscillating circuit that oscillates between two states 
   B. it has been suggested that sleep-waking is controlled by an analogous
      circuit in the brain (Saper et al., 2001) 

Slide 20: a flip-flop of the electronic variety (in other words, an oscillator)

Slide 21: The Sleep-Waking Flip-Flop
I. VLPA, VLPO, or vlPOA (three abbreviations that mean the same thing = 
   ventrolateral preoptic area (in the anterior hypothalamus--the slide is
   wrong about the location of this nucleus)
   A. Nauta (1946) - destruction of the vlPOA produced insomnia, coma, and death
   B. Sterman & Clemente (1962) - electrical stimulation of the vlPOA produced,
      drowsiness, EEG synchrony, and sleep
   C. activity of single neurons in the vlPOA increases during sleep, and in
      sleep-deprived animals they show especially high rates of activity

Slide 22: The Sleep-Waking Flip-Flop
I. hypocretin/orexin neurons may act to stabilize the flip-flop in the
   waking state
II. Carlson suggests that this may be what keeps you awake during boring
    lectures! 

Slide 23: What Controls the Orexinergic Neurons? 
I. biological clock neurons in the hypothalamus (see next section) 
II. hunger-related signals activate orexin neurons 
III. satiety-related signals inhibit orexin neurons 
IV. the VLPA (vlPOA) also inhibits orexin neurons 

Slide 24: Adenosine
I. sleepiness may be caused by the accumulation of adenosine 
 
Slide 25: Neural Control of REM Sleep 
I. physiological signs heralding REM sleep 
   A. PGO waves first
   B. desynchrony second
   C. REMs and muscular paralysis third

Slide 26: Neural Control of REM Sleep 
I. the peribrachial area in the pontine RF 
   A. surrounds the brachium conjunctivum (superior cerebellar peduncle) in the
      anterior pons 
   B. cells here are most active during REM sleep, and are also active during
      waking - they use ACh as their neurotransmitter 
   C. these cells produce the neocortical activation that occurs during REM,
      but they do not turn REM sleep on (as was once believed) 

Slide 27: Neural Control of REM Sleep 
I. these cells use ACh as their neurotransmitter 
   A. ACh agonists facilitate REM sleep 
   B. ACh antagonists inhibit REM sleep 
II. these cells control some of the phenomena of REM sleep, but do not control 
    REM itself (as we'll see) 

Slide 28: REM-on cells
I. REM-on cells are not in the peribrachial region of the pons, as suggested in
   a previous edition of this textbook! 
II. Rather, the sublaterodorsal nucleus, an AChergic nucleus near the locus
    coeruleus, contains the REM-on neurons. 

Slide 29: The REM Sleep Flip-Flop 
I. the REM-On region 
   A. sublaterodorsal nucleus (SLD) 
   B. in the dorsal pons just ventral to the locus coeruleus 
II. the REM-Off region 
   A. ventrolateral periaqueductal gray matter (vlPAG) 
   B. in the dorsal midbrain 
III. interconnected by mutually inhibitory GABAergic neurons 

Slide 30: The REM Sleep Flip-Flop 
I. orexinergic neurons in the lateral hypothalamus have an excitatory effect on
   the REM-Off region - during waking this keeps REM turned off 
II. serotonin and norepinephrine also excite this region 

Slide 31: The REM Sleep Flip-Flop 
I. at sleep onset these excitatory influences on REM-Off are diminished 
II. during SWS the 5-HT and NE inputs gradually diminish to zero 

Slide 32: Control of REM Sleep 

Slide 33: Control of REM Sleep 
I. description of a cat with lesions in the subcoerulear nucleus 
II. REM sleep and procedural learning (again) 
    "The fact that our brains contain an elaborate mechanism whose 
    sole function is to keep us paralyzed while we dream...suggests that  
    the motor components of dreams are as important as the sensory 
    components.  Perhaps the practice our motor system gets during 
    REM sleep helps us to improve our performance of behaviors we 
    have learned that day." - Carlson, p.235 

Slide 34: Next topic: Biological Rhythms