1. The Hypothalamus

3. Functions of hypothalamus
Endocrine function
Caloric balance
Osmolarity balance
Thermal regulation
Autonomic balance
Sleep
Affective behavior
Memory
Somatic movements

11. Anatomy of Hypothalamus
Figure 29-4, textbook
Anterior  posterior: 4 regions
preoptic area
supraoptic region
tuberal region
mammillary region
Medial  lateral: 2 zones
medial zone nearest III ventricle
lateral zone
poorly defined nuclei
prominent medial forebrain bundle connecting hypothalamus to other areas
lateral zone will not be considered further; all names nuclei except for lateral preoptic area are in the medial zone

12. Preoptic area
Medial preoptic: LHRH
Lateral preoptic: motor control

13. Motor connections of hypothalamus

14. Supraoptic region Paraventricular: oxytocin and vasopressin (ADH)
Anterior: heat dissipation
Supraoptic: oxytocin and vasopressin (ADH)
Suprachiasmatic: circadian rhythms
Paraventricular: oxytocin and vasopressin (ADH)
Anterior: heat dissipation
Supraoptic: oxytocin and vasopressin (ADH)
Suprachiasmatic: circadian rhythms

15. Tuberal region Dorsomedial: “sham rage” Ventromedial: satiety center
Arcuate: releasing hormones and inhibiting hormones

16. Mammillary region Posterior nucleus: heat conservation
Mammillary nucleus: learning and memory
Posterior nucleus: heat conservation
Mammillary nucleus: learning and memory

17. Table 30-1 The Effect of Stimulation or Lesion of the Principal
Hypothalamic Nuclei
Nucleus
Stimulation of
Lesion of
Suprachia. n.
Adjusts circadian rhythms
Abolishes circadian rhythms
Supraoptic n.
Paraventri. n.
Increased blood pressure
Diabetes insipidus
Lat. Hypotha. n.
Increased feeding
Decreased feeding
Ventromedial n.
Dorsomedial n.
Sham rage
Decreased aggression & feeding
Mammillary body ?
Short-term memory is not processed into long-term memory

18. Plans for Action
(prefrontal cortex)

19. Functions of the prefrontal cortex:
1) Planning
This is the area where volition, thinking ahead, problem
solving are located. Before you can have these, and do them
flexibly, fluently, adaptively, have to inhibit more primitive,
automatic, instinctive behavior patterns; hence
2) Inhibition
3) Selectivity
‘I will do this, I will not do that’

21. Phineas Gage

23. Prefrontal Cortex Damage:
Lack of foresight
Frequent stubbornness
Inattentive and moody
Lack of ambitions, sense of responsibility, sense of propriety (rude)
Less creative and unable to plan forthe future

24. Sleep

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

27. 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

28. Hypocreatin (orexin)

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

31. Narcolepsy VS Insomnia

32. 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].

34. 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.

36. SCN and sleep Wild type animal with period of ~24h Tau mutant
Basics of Sleep Guide: Chronobiology
SCN and sleep
6/26/2018
6/26/2018
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 36 36

37. Coffee

38. Coffee
During waking, brain consume ATP

39. Coffee
During waking, brain consume ATP
adenosine

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

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