1
Q
LO
A
- Define Sleep and explain its contribution to health and well-being
- Discuss the regulation of sleep
- Illustrate the homeostatic and circadian control of sleep using the model organism Drosophila melanogaster as an example.
2
Q
What is sleep?
A
- Altered consciousness
- Reduced movement and responsiveness
- Typical posture
- Homeostatic regulation
- Daily rhythmicity
3
Q
What is more specific to sleep in higher animals?
A
- Brainwave patterns
- Loss of muscle tone during sleep
- Sporadic eye movement (REM sleep)
4
Q
Where are cholinergic neurons found?
Tell me about their role in sleep
A
They are found near the junction of the pons and midbrain
- Stimulate cholinergic neurons in reticular activating system then experiments on cats showed the brain activity would shift from being sleep to more awake
- Stimulate thalamus then the slow waves will mimic those in non-REM sleep from awake state
- Brain activity in brain by stimulation or inhibition of different areas of the brain
5
Q
What is an EEG used for?
A
- Can measure brain waves from different locations in the head
- slow wave patterns during non REM sleep are a result of synchronised firing in regions of the brain
6
Q
An EEG recording was taken during the 1st hour of sleep, tell me the different waves seen over the one hour period, and at what times they were seen. Tell me about the frequency range for each wave type
A
7
Q
Whats are sleep spindles?
A
Sleep spindles are bursts of neural oscillatory activity that are generated by interplay of the thalamic reticular nucleus (TRN) and other thalamic nuclei during stage 2 NREM sleep in a frequency range of ~11 to 16 Hz (usually 12–14 Hz) with a duration of 0.5 seconds or greater (usually 0.5–1.5 seconds).
8
Q
tell me some features of NREM sleep?
A
- Reduced physiological activity
- Shift to Parasympathetic activity
- Thermoregulation maintained
9
Q
Tell me about the average sleep cycle
A
- REM periods every 90-120min
- First REM period is shortest
- Most REM sleep occurs late
- Most deep sleep (stage3,4) early
10
Q
How does the sleep cycle vary with age?
A
- Similar amount of REM sleep
- Diminishing stage 3,4 sleep
- Increasing sleep fragmentation
- All varies across ages
11
Q
Whats a polysomnogram?
A
Polysomnography, also called a sleep study, is a comprehensive test used to diagnose sleep disorders. Polysomnography records your brain waves, the oxygen level in your blood, heart rate and breathing, as well as eye and leg movements during the study.
12
Q
What stage of sleep is dreaming associated with?
A
REM
13
Q
In what ways does REM resemble the wake state?
A
- brain activity
- heart rate
- respiration
14
Q
In whats ways does REM sleep diverge from the wake state?
A
- eye movement
- muscle tone less
- suspended thermoregulation (core temp drops and peripheral increases)
- penile erection/vaginal lubrication
15
Q
Tell me about the suppression of somatosensory response and muscle relaxation during REM sleep
A
- GABA NT released which is an inhibitory signal
- Inhibition of different centres that are signalling using a variety of NT
- One in diagram uses serotonin (5-HT) and noradrenaline
- Cholinergic centre and glutamatergic centres also present
- Glycinergic centre goes down to spinal cord
- Due to GABAergic signal initially all of this connected will suffer from inhibition
- Get inhibition of lower motor neuron pathways which results in paralysis during sleep
- Other way around, if go to cortex there is 2 negatives which makes a positive so cortical activity is no repressed which is why we see, with electrodes, a similar brain activity pattern as to when we are asleep
- Explains why relax body but keep brain active when we are asleep
16
Q
What are the areas that are inactivated/ activated during REM sleep?
A
17
Q
Tell me 4 areas of the brain associated with arousal and what are the NT expressed/secreted from here?
A
- Cholinergic nuclei: ACh
- Raphe nuclei: 5-HT/ serotonin
- Tuberomammillary nucleus of hypothalamus: Histamine
- Locus Coeruleus: Noradrenaline
18
Q
Label the following areas/ nuclei and what part of sleep they are involved with
(bottom left)
A
19
Q
Toggle switch
A
20
Q
Sleep/wake toggle switch
A
21
Q
An experiment was done on rats to look at the effects caused by depriving one of sleep. The experiment had 2 rats on a disc. One rat was not allowed to sleep where as the other was. When the no sleep rat would fall asleep, the disc it was on would spin and the rat would fall in the way and wake up. What are some of the side effects the rat experienced from sleep deprivation?
A
- debilitated appearance
- skin lesions
- swelling of the paws
- loss of motor control
- loss of EEG amplitude
- respiratory symptoms
- stomach ulcers
22
Q
Tell me some cognitive impairments of sleep disruption
A
- Inattention
- Changes in cortical EEG responses
- Slower computational speed
- Impaired verbal fluency
- Reduced creativity
- Reduced abstract problem solving
- Learning issues
- Lower IQ scores
23
Q
Name some examples of sleep disorders (dyssomnia)
A
- Primary Insomnia
- Primary Hypersomnia
- Narcolepsy
- Breathing Related Sleep Disorder
- Circadian Rhythm Sleep Disorder
24
Q
Tell me about primary insomnia…
A
Primary insomnia (1-10% population)- most common one
- Initial (Anxiety disorders)
- Middle (Maintenance)
- More common in women & elderly
- Sudden onset
- Continuation (vicious cycle) so hard to deal with
- Drug abuse can make this worse as makes everything heightened
25
Tell me about **narcolepsy**...
* Daytime sleepiness
* ‘Sleep attacks’
* Cataplexy (emotional trigger)
* Sleep paralysis
* Excessing dreaming & waking at night
* **Orexin signalling defect** (orexin associated with the lateral hypothalamic area)- this was found by the research in narcoleptic dogs as slip out of wake state and into REM sleep. Turn over or neurodegeneration problems
26
What are examples of breathing-related sleep disorders?
1. Primary snoring
2. Obstructive sleep apnoea
27
What **primary snoring**?
Tissues in the back of the throat vibrate
28
Tell me about **obstructuve sleep apnoea** and some risk factors associated with this disorder
What advice is given to people with this disorder?
**Obstructive Sleep Apnoea**
* what it is: Blocked airway (blood oxygenation↓, wake)
* risks: risk↑ cardiovascular disease, (pre-)diabetes, depression
* advice: losing weight and not sleeping on the back are advice for people with sleep apnoea to prevent the airway becoming blocked
29
Name some circadian rhythm sleep disorders
* **Normal sleep wake cycle**
* **Non-24h sleep wake syndrome:** Non-24-hour sleep-wake disorder (N24) is a circadian rhythm sleep disorder in which an individual's biological clock fails to synchronize to a 24-hour day. Instead of sleeping at roughly the same time every day, someone with N24 will typically find their sleep time gradually delaying by minutes to hours every day.
* **Irregular sleep wake syndrome:** disrupted sleep that’s often unstructured. Likely sleep for under four hours at a time
* **Delayed sleep phase syndrome:** Delayed sleep-wake phase disorder (DSWPD) is a disorder in which a person's sleep is delayed by two or more hours beyond the socially acceptable or conventional bedtime. This delay in falling asleep causes difficulty in waking up at the desired time.
* **Advanced sleep phase syndrome:** Advanced sleep-wake phase disorder (ASP) is one of several circadian rhythm sleep disorders. These disorders occur in people who sleep at times that seem to be out of order with “normal” sleep times. People with ASP have an “early bird” circadian clock. They fall asleep several hours before a normal bedtime.
30
What two ways control sleep?
* Rhythmically (C)
* Homeostatically (S)
31
What is meant by **eclosion**
The emergence of an adult insect from a pupa or a larva (or nymph) from an egg is called eclosion
32
What is the evidence for a daily timekeeper (circadian clock)?
* Control of overt rhythms
* Entrainment
* Free-running rhythms
* Temperature compensation
33
The molecular clockwork: delayed negative feedback of gene expression
34
SCF-mediated protein degradation
35
SCF-mediated protein degradation of per
36
SCF-mediated light induced protein degradation of TIM
37
Light in early night 'late dusk': phase delay
38
Light in late night 'early dawn': phase advance
39
Remarkable conservation of animal clocks
40
Clock-controlled gene link to output
41
Circadian regulation of sleep (drosophila)
42
Homeostatic regulation of sleep (drosophila)
43
Unnotated abbreviations
* EOG: ElectroOculoGram
* EMG: ElectroMyoGram
* NE: Norepinephrin
* Ach: Acetylcholine
* Glu: glutamate
* 5-HT: 5-Hydroxytryptamine (Serotonin)
* GABA: Gamma-Aminobutyric Acid
* His: Histamine
* VLPO: VentroLateral PreOptic Nucleus
* MPOA: Medial Preoptic Area
* vPAG: ventral PeriAqueductal Gray
* LC: Locus Coeruleus
* LDT: LateroDorsal Tegmental Nucleus
* PPT: PedunculoPontineTegmental Nucleus
* TMN: TuberoMammillary Nucleus
* LH: Lateral Hypothalamus
* ORXN: Orexin
* Clk: Clock
* Cyc: Cycle
* Bmal1: Brain and Muscle ARNT-like 1
* Per: Period
* Tim: Timeless
* Cry: Cryptochrome
* Dbt: Doubletime
* CK1d/e: Casein Kinase 1d/e
* Jet: Jetlag
* Slmb: Supernumerary Limbs B
* Ub: Ubiquitin
* Cul-1: Cullin 1
* E1,2: Ubiquitin Ligase 1,2
* s-LNv: small ventral Lateral Neuron
* LNd: dorsal Lateral Neuron
* DN1: Dorsal Neuron 1
* PDF: Pigment Dispersing Factor
* VIP: Vasoactive Intestinal Peptide
* sNPF: small NeuroPeptide F
* NPY: Neuropeptide Y
* DH44: Diuretic Hormone 44
* CRH: Corticotropin Releasing Hormone
* HUG: Hugin
* DA: Dopamine
44
Sleep homeostat in dorsal fan-shaped body
45
**Sexual dimorphism and behaviour**
**LO**
* **Illustrate the relevance of sexual dimorphism in animal brains and behaviour**
* **Use the example of courtship behaviour in fruit flies to:**
1. **Explain the role of sex determination in courtship behaviour**
2. **Show how complex behavioural patterns arise from the interaction between innate behavioural sequences and sensory inputs**
3. **Explain the molecular principles and neural organization of courtship behaviour**
46
How does the male Manduca Sexta detect a female?
What structures are present in the male than in the female and what does this have a role in?
* Male can detect female pheromone at low concentrations
* Males have a large macroglomerula complex which is absent in female (role?)
* Male antenna onto fame results in the formation of complex which brings up interesting questions
47
Whats meant by **sexual dimorphism**?
Sexual dimorphism is the condition where the two sexes of the same species exhibit different characteristics beyond the differences in their sexual organs. The condition occurs in many animals and some plants.
48
State a sexual dimorphism in birds
Male songbirds (not simple bird calls like we hear every day but a more elaborate sound)
49
What does the male songbird signal to females?
* Species
* Individual identity
* Location
* Readiness to mate
50
What do male songbirds compete with rivals for?
* Territory
* Neighbor vs stranger
51
Tell me about the song motor pathway in the brain
* Reduced in ♀♀
* Song production
* Testosterone\>BDNF (Brain-derived neurotrophic factor) \>
* Seasonal neurogenesis
52
Tell me some features/ characteristics of the birdsong
* Long and complex
* Made up of syllables
* Expiration
* Tympanic membrane vibration
* Pitch and volume modulation
53
How does a male songbird sing?
The avian vocal organ is called the **syrinx**; it is a bony structure at the bottom of the trachea (unlike the larynx at the top of the mammalian trachea). The syrinx and sometimes a surrounding air sac resonate to sound waves that are made by membranes past which the bird forces air. The bird controls the pitch by changing the tension on the membranes and controls both pitch and volume by changing the force of exhalation. It can control the two sides of the trachea independently, which is how some species can produce two notes at once.
54
how does a birds song mature?
NB. Many of these areas are diminished in the female brain
55
Robust nucleus of the Arcopallium (RA)
56
Drosophila sex determination
57
Drosophila innate mating behaviour
58
What neurons were found in drosophila to be involved with courtship
Fru neurons
59
Transgenic GAL4/UAS expression
Tell me about targeted reproter gene expression in creating two transgenes
* P-Gal4, expressing the foreign transcription factor GAL4 in the pattern of promotor P
* UAS-Transgene, which uses GAL4 binding sites (UAS) to produce transgene expression
60
Tell me about the spatial organisation of FruM neurons
**Spatial organisation of FruM neurons**
* NOTE: ♀♀ have Fru-Gal4 expressing neurons (important for receptivity), but these do not express FruM
* Females have Fru-Gal4 expressed by they don’t produce the male Fru protein
61
FruM-marked olfactory (smell) pathways
62
FruM- marked gustatory (taste) pathways
63
More about Fru...
64
What are some possible requirement for male courtship behaviour?
* Male-specific organs?
* Male specific neurons?
* Male-specific molecular signals?
* Male-specific patterns of neural activity?
65
Tell me about courtship requirements in male drosophila
* The female brain is equipped with latent circuitry underlying male-like behaviour
* Females with activated **dsxf brain neurons** court males and females and other Drosophila species
* This function maps to **dsx-pC1 brain neurons.**
* **Cuticular methyl pheromones** trigger male courtship behaviours in activated females
66
Drosophila male courtship circuit
67
Is the male brain dispensible for copulation (sexual intercourse)?
Investigate dsx circuitry in ventral nerve cord
68
A Dsxm male copulation circuit
* Drosophila male has 650 dsxm neurons, with specific subsets controlling distinct steps of the courtship ritual
* Circuit of doublesex-expressing neurons in the equivalent of the spinal cord controls copulation itself:
- Glutamatergic motor neurons that coordinate the joining of genitals
- GABA-ergic inhibitory interneurons that promote release of genitals by opposing the motor neurons
- Mechanosensory neurons that connect to brain and abdominal ganglion
69
Control of female mating receptivity
70
Rejection of courtship by mated females
71
Courtship conditioning in males
72
Tell me about courtship receptivity and conditioning in males
* Drosophila virgin ♀ has Fru-Gal4-marked sensory neurons that promote receptivity.
* Courtship song and cVA promote receptivity via pC1 neurons.
* Transfer of Sex Peptide during mating reduces receptivity in mated ♀ by inactivating the SAG neurons, which connect to pC1.
* pC1 connect to vaginal plate opening descending neurons.
* Repeated rejection by mated ♀ conditions ♂ to reduce courtship via their FruM mushroom body g neurons.
73
Unannotated abbreviations
**Unannotated abbreviations**
* BDNF: Brain-Derived Neurotrophic Factor
* HVC: Higher Vocal Centre
* RA: Robust nucleus of the arcopallium
* LMAN: Lateral magnocellular nucleus of the anterior nidopallium
* DLM: DorsoLateral nucleus of anterior thalamus
* Rt: nucleus rotundus
* SXL: SEX LETHAL
* TRA: TRANSFORMER
* TRA-2: TRANSFORMER 2
* MSL-2: MALE SPECIFIC LETHAL
* IX: INTERSEX
* HER: HERMAPHRODITE
* DSX: DOUBLESEX
* FRU: FRUITLESS
* UAS: Upstream Activating Sequence
* VNC: Ventral Nerve Cord
* CD8: Cluster of Differentiation 8
* GFP: Green Fluorescent Protein
* cVA: 11 cis Vaccenyl Acetate
* ORN: Olfactor Receptor Neuron
* GRN: Gustatory Receptor Neuron
* PN: Projection Neuron
* GPN: Gustatory Projection Neuron
* JON: Johnston’s Organ
* APN: Auditory Projection Neuron
* ND: (7Z,11Z)-Nonacosadiene
* HD: (7Z,11Z)-Heptocosadiene
* 7T: (Z)-7-tricosene
* TRPA1: Transient Receptor Potential A1
* vGlut: vesicular Glutamate transporter
* DA: dopamine
* GABA: Gamma-Aminobutyric Acid
* vpoDN: vaginal plate opening descending
74
**Sexual dimorphism and behaviour**
**LO**
* **Illustrate the relevance of sexual dimorphism in mammalian brains and behaviour**
* **Describe the role of steroid hormone signalling in sex determination and behaviour**
75
Tell me about sexual dimorphism and behaviour of Aspidoscelis uniparens whiptail lizard (all ♀)
* Parthenogenesis (development from unfertilized eggs)
* Pre-meiotic endoreplication (2n oocytes)
* Courtship behaviour stimulates ovulation
* Progesterone associates with ♂-like behaviour
* Progesterone acts in MPOA-equivalent area of hypothalamus
* Oestrogen associates with ♀-like behaviour
* Oestrogen acts in VMH-equivalent area of hypothalamus
76
Human sex determination
77
Tell me about some genetic disorders resulting in intersexuality in humans
Name the syndrome, the mutation that occured and the phenotype seen
78
Signalling via steroid hormone receptors
79
Actions of steroids on the brain
80
Oestradiol-sensitive neurons in the rat brain
81
Steroid receptors in the rat brain
82
Steroid action in rodent utero
83
Tell me about steroid action on sexual dimorphism in the rodent brain in normal male/female and neonatal treated
84
Tell me about territorial marking of rodens of urine in their cage
85
Brain/gonad interaction during puberty and adulthood
86
Impact of steroids of neuronal growth and differentiations
87
Impact of steroids on dendritic spines in ♀ hippocampus
88
Impact of oestrogen on hippocampal synaptic transmission
89
Tell me the impact of testosterone on cultured rat pelvic ganglion
90
Sexual dimorphism in rodent CNS
91
Sexual dimorphism in human CNS
92
**LO II**
* **Illustrate the relevance of sexual dimorphism in mammalian brains and behaviour**
* **Describe the role of steroid hormone signalling in sex determination and behaviour.**
* **Discuss neural pathways underlying sexual and parental behaviour**
* **Provide examples of neuropeptide regulation of social behaviour**
93
Sexual dimorphism in rodent hypothalamus
94
Tell me about sexual differentiation in the spotted hyena
* ♀ larger, more aggressive than ♂
* ♀ socially dominant
* ♀ clitoris (as large as ♂ penis) for:
- urination
- receiving semen
- giving birth
* Deficiency in placental aromatase
* Mother makes androstenedione (this is sensed by foetal exposure of both genders)
* ♀ pups fight siblings from birth
* ♀ have feminine SDN-POA and SNB
* Anti-androgen treatment in utero
- ♂ foetus: penis → clitoris, no prostate, ♀-like bulbocavernosus muscle, Onuf’s nucleus↓
- ♀ foetus: size↑ & elasticity↑ of urogenital meatus (opening), clitoris length↓, glans diameter↑
95
Sexual dimorphism in rodent brain
96
Sexual dimorphism in rodent brain
97
Aromatase+ BNST neurons identify sex of intruder
98
VMH facilitates lordosis in ♀ rats
99
PR+ VMH regulates sexually dimorphic behaviour
100
Sexual experience regulates sexually dimorphic behaviour
101
Neural circuits for sexual behaviour in rodents
102
Pup Retrieval in ♀ mice
103
Impact of MPOAGal neurons on parental behaviour
104
Neuropeptides for sexual behaviour
105
Pair bonding in prairie voles
106
Brain areas (de)activated by a picture of one’s beloved
107
Sex differences in human cognition
