1. Organisation of the motor system
Visual cortex
Somatosensory
cortex
Cerebellum
Basal
ganglia
Prefrontal cortex
Supplementary
motor cortex
Pyramidal
tract
Premotor
cortex
Primary
Motor nuclei
of the thalamus
Brainstem
Extrapyramidal
Motor pathways

2. Motor system includes Tracts Basal Ganglia (regulator)
Corticospinal tract (Pyramidal tract )
Extra-pyramidal system
Basal Ganglia (regulator)
Cerebellum (regulator)

3. Motor regulators Motor control systems outside the cortex
Cerebellum -controls neural ‘programs’ for the executionl of skilled movements
Basal ganglia - a group of subcortical forebrain nuclei (caudate nucleus, putamen (= striatum), globus palludus, subthalamic nucleus) - modulate patterns of motor activity

5. MOVEMENT DISORDERS
Parkinson disease
Huntingtons disease

6. PARKINSONS DISEASE
Effects dopaminergic neurons
Neurons are lost from substantia nigra
Rarely presents before 50 years
Neurodegenerative disease

7. Neuropathology of Parkinson’s disease
nigro-striatal pathway degeneration
leading to a depletion of striatal dopamine
some degeneration of other dopamine pathways too
Striatum
Dopamine
Glutamate
GABA X

8. CLINICAL FEATURES
Characterized by:
Tremors
Rigidity
bradykinesia

9. X Huntington’s disease Onset of symptoms usually at 30 to 45 years
Genetically determined (single dominant gene)
Causes degeneration of the output neurones from the striatum, reducing inhibitory modulation of motor function
Progressive disease causing involuntary muscle jerks
Striatum
Dopamine
Glutamate
GABA X

10. HUNTINGTONS DISEASE
Inherited disorder
Autosomal dominant
Males females equally affected
Presents during the 4th decade
Chorea which worsens with time
Cognitive disorders
Dementia

11. Motor control systems outside the cortex
Cerebellum -controls neural ‘programs’ for the executionl of skilled movements
Basal ganglia - a group of subcortical forebrain nuclei (caudate nucleus, putamen (= striatum), globus palludus, subthalamic nucleus) - modulate patterns of motor activity

12. GROSS STRUCTURE

13. Feed-back and feedback
control circuits

14. Cerebellar connections
Input:
Sensory cortex (somato, visual)
Vestibular system
Spinocerebellar tract
Output:
Motor cortex
Thalamus motor nuclei
Extra-pyramidal tracts

15. The main functions of cerebellum:
body equilibrium
regulation of muscle tone
coordination of movements

16. A t a x i a
means disturbances of equilibrium of the body and coordination of movements.
Cerebellum lesion produces cerebellar ataxia

17. Cerebellar ataxia Attactic gait – patient can’t to walk
Disorders of equlibrium – patient can’t to stand
Intention tremor – is dynamic tremor (it is more expressed while moving and disappears while rest)
Nystagmus
Dysmetria (disturbed ability to gauge distances)

22. Sleep

23. Why Do We Need Sleep? Adaptive Evolutionary Function
safety
energy conservation/ efficiency
Restorative Function
body rejuvenation & growth
Brain Plasticity
enhances synaptic connections
memory consolidation

25. The ascending arousal system promotes wakeB. A.
(A) In the 1970s and 1980s, the neurochemistry of several brainstem ‘arousal’ centers was elaborated. In the contemporary view, the ascending arousal system consist of noradrenergic neurons of the ventrolateral medulla and locus coeruleus (LC), cholinergic neurons (ACh) in the pedunculopontine and laterodorsal tegmental (PPT/LDT) nuclei, serotoninergic neurons (5-HT) in the dorsal raphe nucleus (DR), dopaminergic neurons (DA) of the ventral periaqueductal gray matter (vPAG) and histaminergic neurons (His) of the tuberomammillary nucleus (TMN). These systems produce cortical arousal via two pathways: a dorsal route through the thalamus and a ventral route through the hypothalamus and basal forebrain (BF). The latter pathway receives contributions from the orexin and MCH neurons of the lateral hypothalamic area (LH) as well as from GABA-ergic or cholinergic neurons of the BF. Note that all of these ascending pathways traverse the region at the midbrain-diencephalic junction where von Economo observed that lesions caused hypersomnolence.
Fuller, PM, Gooley JJ, Saper CB. Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms 21(6): (2006)
Slide by Patrick Fuller, PhD and Jun Lu, PhD
Modified from Fuller et al., J Biol Rhythms, 2006

26. Hypocreatin (orexin)

28. Sleep/Waking “Flip-Flop”
vlPOA= ventrolateral preoptic area
ACh = acetylcholine
NE = norepinephrine
5-HT = serotonin

29. Narcolepsy VS Insomnia

30. 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
Melatonin, ramelteon, and agomelatine are all agonists for melatonin 1 (MT1) and melatonin
2 (MT2) receptors [87]. Ramelteon has an affinity for both receptors that is 3–16 times greater
than melatonin, and it has a longer half-life. Agomelatine also has a high affinity for melatonin
receptors, in addition to acting as an antagonist at serotonin 5-HT2C receptors to decrease
anxiety as well as promote sleep. Both MT1 and MT2 play a role in sleep induction; MT1
activation suppresses firing of SCN neurons, and MT2 receptors are involved in entraining
circadian rhythms. Melatonin and the SCN impact sleep and wake in several ways. The SCN
receives light signals from the retina, which are transmitted to the dorsal medial hypothalamus
(DMH). The DMH acts as a relay center for signals to regions involved in sleep and wake
maintenance, including inhibitory inputs to the VLPO and excitatory inputs to the LC [14,
95]. Melatonin acts through MT1 receptors to suppress firing of SCN neurons, thereby
disinhibiting the sleep-promoting neurons in the VLPO, suppressing excitatory signals to
wake-promoting regions, and increasing sleepiness [87].

32. Biological Clocks Suprachiasmatic nucleus Pineal gland
A nucleus situated atop the optic chiasm responsible for organizing circadian rhythms.
Pineal gland
A gland attached to the dorsal tectum; produces melatonin and plays a role in circadian and seasonal rhythms.

34. SCN and sleep Wild type animal with period of ~24h Tau mutant
Basics of Sleep Guide: Chronobiology
SCN and sleep
5/18/2018
5/18/2018
Wild type animal
with period of ~24h
Tau mutant
with period of ~20h A
SCN lesioning B
Transplanting SCN
of donor with ~20-h period C
SCN lesioning
abolishes circadian rhythm
Wild type animal acquires
period of donor (~20h)
Modified from Ralph and Lehman, Trends Neuro 1991
Scheer-Shea Set #8 34 34

35. Coffee

36. Coffee
During waking, brain consume ATP

37. Coffee
During waking, brain consume ATP
adenosine

38. Coffee During waking, brain consume ATP adenosine
Adenosine bind to A1 receptor
Inhibit acetylcholine neurons

39. Coffee During waking, brain consume ATP adenosine
Adenosine bind to A1 receptor
Inhibit acetylcholine neurons
Caffeine and Theophylline are A1 antagonist

40. Sleep stages
Awake
Stage 1
Stage 2
Stage 3
Stage 4
Slow wave sleep

41. Sleep stages Awake Stage 1 Stage 2 Stage 3 Stage 4
Rapid eye movement sleep (REM)
Slow wave sleep
(NREM)

42. Types and Stages of Sleep: NREM
Stage 1 – eyes are closed and relaxation begins; the EEG shows alpha waves; one can be easily aroused
Stage 2 – EEG pattern is irregular with sleep spindles (high-voltage wave bursts); arousal is more difficult

43. Stage 3 – sleep deepens;; theta and delta waves appear; vital signs decline; dreaming is common
Stage 4 – EEG pattern is dominated by delta waves; skeletal muscles are relaxed; arousal is difficult

45. REM Sleep Presence of beta activity (desynchronized EEG pattern)
Physiological arousal threshold increases
Heart-rate quickens
Breathing more irregular and rapid
Brainwave activity resembles wakefulness
Genital arousal
Loss of muscle tone (paralysis)
Vivid, emotional dreams
May be involved in memory consolidation

47. REM Dreaming NREM Dreaming “vivid and exciting” “just thinking”
~3 per night
Longer, more detailed
Fantasy world
nightmares
“just thinking”
Shorter, less active
Logical, realistic

48. Dream theories Activation synthesis theory Continual activation theory
Sensory experiences are fabricated by the cortex as a means of interpreting signals from the PGO activity.
Continual activation theory
Encoding of short term into long-term memories.
NREM sleep processes the conscious-related memory (declarative memory),
REM sleep processes the unconscious related memory (procedural memory).
Dream theories

49. Sleep Disorders insomnia sleep walking, talking, and eating
nightmares and night terrors
narcolepsy
sleep apnea
IM: Activity Handout 6.2: Which Sleep Disorder Is It? 49

50. Sleep Disorders
Insomnia: persistent problems in falling asleep, staying asleep, or awakening too early
Sleep Apnea: repeated interruption of breathing during sleep
Narcolepsy: sudden and irresistible onsets of sleep during normal waking hours

51. Sleep disorders
Nightmares: anxiety-arousing dreams occurring near the end of sleep, during REM sleep
Night Terrors: abrupt awakenings from NREM sleep accompanied by intense physiological arousal and feelings of panic

52. Sleep Disorders Somnambulism…sleepwalking
40% of children will have an episode, peaking at between years of age;
Can be induced if arouse children during NREM;
associated with complete amnesia,
Occurs within 2 hours of falling asleep.. EEG..reveals both waking and sleep signals. Considered benign.

53. Coma & Brain death Definition:
Greek in origin – “deep sleep or trance”
It refers to an unconscious state characterised by a lack of both arousal and responsiveness

54. language

55. Broca Aphasia (Expressive aphasia)
Left hemisphere
Broca's aphasia - Sarah Scott - teenage stroke

56. Wernicke Aphasia (Receptive aphasia)
Left hemisphere
Wernicke's Aphasia Interview with Amelia Carter

57. (right hemisphere)

58. Prosody of speech
(right hemisphere)