MIDTERM REVIEW 2P37

Monday, February 10, 2025 8:55 PM

LECTURE TWO:

BRAIN DAMAGE AND NEUROPLASTICITY

Causes of Brain Damage

- Possible causes of widespread (diffuse) brain damage include
○ Prolonged hypoxia (shortage of oxygen)
○ Poisoning
○ Infection
- Common causes of focal or localized brain damage include
○ Cardiovascular disorders
○ Closed-head injuries
○ Tumors

Cerebrovascular Disorders
- Strokes are sudden onset cerebrovascular disorders that cause brain damage
- 5th leading cause of death and the most common cause of adult disability
○ Common consequences are amnesia, aphasia (language difficulties), paralysis
coma
- Goal of treatment shortly after a stroke is to save the tissue that lies within the
penumbra
- Infarct: area of dead or dying tissue (proximal to stroke)
- Penumbra: dysfunctional area surrounding the infarct; tissue in that area may eithe
recover or die

○
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Stroke Types
- Ischemic
○ Disruption of blood supply
○ Clots
○ 87% of all strokes
- Hemorrhagic
○ Bleeding in the brain

Cerebrovascular Disorders
- Cerebral hemorrhage: blood vessel ruptures
- Aneurysm: a weakened point in a blood vessel that makes a stroke more likely
- May be congenital (present at birth) or due to high blood pressure, smoking, or infe
- Two types of aneurysms:

- Cerebral hemorrhaged treatments

○ Clipping

○ Coiling
ection
 ○ Coiling

- Cerebral ischemia: disruption of blood flow to an area to the body

○ Thrombosis: a clot ("thrombus") formed at site
○ Embolism: a clot ("embolus") forms elsewhere and moves to the brain via
bloodstream
○ Arteriosclerosis: thickening of arterial walls (i.e. narrowing of blood vessels)
to fat, cholesterol, and calcium deposits

Ischemia-Induced Brain Damage

- Excitotoxicity
- Excessive neurotransmitter release (esp. glutamate) that spreads out from initial
ischemic site and ultimately results in neuronal cell death
- Big picture
○ Develops over time (not instantaneous)
○ Does not occur equally in all parts of the brain (e.g. more likely in some parts
the hippocampus)
○ Mechanisms of ischemia-induced damage vary between brain structures

Closed-Head Injuries
- Brain injuries that do not penetrate the skull
- Contusions
○ Involve damage to the cerebral circulatory system, producing internal
hemorrhaging and a resultant hematoma ("bruise")
- Concussions
○ Diagnosis given following head injury in absence of overt evidence of contus
or other structural damage (may or may not involve loss of consciousness)

Some Neuroanatomy
- Meninges
○ Protective membranes that surround the brain
§ Dura mater
§ Arachnoid mater
§ Pia mater
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 - Meninges
○ Protective membranes that surround the brain
§ Dura mater
§ Arachnoid mater
§ Pia mater

Contusions
- Brain shifts/herniations
- Dural reflections
○ Between the cerebral hemispheres (falx cerbri)
○ Between the cerebellum and inferior occipital lobe (tentorium cerebelli)
 ○ Between the cerebral hemispheres (falx cerbri)
○ Between the cerebellum and inferior occipital lobe (tentorium cerebelli)

Concussions
- Mild traumatic brain injury (mTBI)
○ Classification
§ Less than 30 minutes of unconsciousness
§ Less than 24 hours posttraumatic amnesia
○ 1.6-3.8 million sporting-related concussions per year in US
○ Single occurrence - good recovery
○ Repetitive - progressive neurological deterioration
○ Once thought to be temporary disturbance of normal brain function
○ We now appreciate that concussions can have long term effects ranging from
hours to years
○ Mechanisms involve diffuse brain injury
§ Structural
§ Chemical
- Chronic traumatic encephalopathy (CTE)
○ Neurodegenerative disease observed in individuals with a history of multiple
injuries (concussions); characterized by dementia and severe mood disturban

Brain Tumor
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 § Chemical
- Chronic traumatic encephalopathy (CTE)
○ Neurodegenerative disease observed in individuals with a history of multiple
injuries (concussions); characterized by dementia and severe mood disturban

Brain Tumor
- A tumor (neoplasm) is a mass of cells that grows independently of the rest of the b
- Tumors can be malignant or benign
- Two broad classes of tumors
○ Encapsulated
○ Infiltrating
- Meningiomas
○ 20% of brain tumors
○ Encapsulated - encased within meninges
○ Usually benign; surgically removable
- Infiltrating tumors
○ Most brain tumors (~80%)
○ Grow diffusely through surrounding brain tissue
○ Malignant; difficult to remove or destroy
○ Glioblastoma (glioma)
§ Most aggressive cancer with brain origin
§ Prognosis: 12-15 months from diagnosis
- Metastatic tumors
○ About 10% of the infiltrating brain tumors grow from tumor fragments carrie
the brain from another body part via the bloodstream
○ Commonly originate from breast cancer or lung cancer

Parkinson's Disease
- Progressive neurodegenerative disorder
○ Affects ~100,000 Canadians (1/500)
○ Described in 1817 by James Parkinson
§ "the shaking palsy"
- Characterized by loss of dopaminergic neurons in the substantia nigra
- Primary classified as motor disorder
○ Poverty of movement (akinesia)
○ Slowness of movement (bradykinesia)
○ Increased muscle tone/rigidity (hypertonia)
○ Resting tremor
- Treatments
○ L-DOPA
§ Levodopa (L-3,4-dihydroxyphenylalanine)
§ Metabolic precursor to dopamine
§ Crosses blood-brain barrier
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 ○ Resting tremor
- Treatments
○ L-DOPA
§ Levodopa (L-3,4-dihydroxyphenylalanine)
§ Metabolic precursor to dopamine
§ Crosses blood-brain barrier
§ Can ease symptoms, but not cure
□ As disease progresses, more L-DOPA required to manage sympto
§ Drug therapy generally becomes ineffective over time
□ Can lead to Levodopa-induced Dyskinesia (LID) : involuntary mu
movements and diminished voluntary movements
○ Deep brain stimulation
§ Only indicated for individuals whose symptoms cannot be adequately
controlled with medications
§ Electrode surgically implanted to stimulate brain
□ Subthalamic nucleus
□ Thalamus
□ Globus pallidus
§ Neurotransmitter/pacemaker delivers impulses that block abnormal elec
signals and alleviate PD motor symptoms

What is Dementia?
- Dementia is the general intellectual deterioration resulting from brain disease or in
○ Memory disorders
○ Personality changes
○ Impaired reasoning
- Alzheimer's Disease (AD) is most common form of dementia
○ Sex difference in occurrence
§ And evidence for sex differences in pathophysiology
○ Risk for dementia increases with age

○
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Alzheimer's Disease Pathophysiology
- Three defining characteristics of Alzheimer's
○ Amyloid plaques
○ Neurofibrillary tangles
○ Substantial decrease in brain volume
- Amyloid Plaques
○ Amyloid (AB) is cleaved from a precursor protein and is normally cleared fro
brain
○ In AD, AB aggregates
§ Forms plaques
§ Damages synapses
§ Induces Tau aggregation
- Neurofibrillary Tangles
○ Tau is a protein that helps stabilize microtubules
○ In AD, Tau aggregates
§ Forms neurofibrillary tangles
§ Leads to microtubule destabilization
§ Spreads to adjacent neurons
- Regional distribution
○ Preferentially accumulates in limbic regions
○ Especially hippocampus

Alzheimer's Disease Biomarkers

om
Alzheimer's Disease Biomarkers
Alzheimer's Disease Treatments
- No cure for AD
○ Available therapies focus on managing symptoms
- Research targeting AB metabolism
○ Many drugs have side effects or show little efficacy

Neuroplastic Responses to Nervous System Damage

- Degeneration: deterioration
- Regeneration: regrowth of damaged neurons
- Reorganization
- Recovery of function

Degeneration
- Anterograde: degeneration of the distal segment between the cut and synaptic term
○ Cut off from cells metabolic center; swells ad breaks off within a few days
- Retrograde: degeneration of the proximal segment between the cut and cell body
○ Progresses slowly; if the regeneration axon makes a new synaptic contact, the
neuron may survive

Neural Regeneration
- Does not proceed successfully in mammals and other higher vertebrates; the capac
for accurate axonal growth is lost in maturity
- Regeneration is virtually nonexistent in the CNS of adult mammals and unlikely, b
possible, in the PNS
○ Schwann cells in the PNS promotes regeneration
§ Neurotrophic factors stimulate growth
§ Cell-adhesion molecules provide a pathway
○ Oligodendroglia in the CNS actively inhibits regeneration

Neural Reorganization
- Reorganization of primary sensory and motor systems has been observed in labora
animals following:
minals

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atory
 § Cell-adhesion molecules provide a pathway
○ Oligodendroglia in the CNS actively inhibits regeneration

Neural Reorganization
- Reorganization of primary sensory and motor systems has been observed in labora
animals following:
○ Damage to peripheral nerves
○ Damage to primary cortical areas
- There is continuous competition for cortical space by functional circuits

Recovery of Function after Brain Damage

- It is difficult to conduct controlled experiments on populations of brain-damaged
patients
- Researchers can't distinguish between true recovery and compensatory changes
- Cognitive reserve (i.e. education and intelligence) is thought to play an important r
recovery of function
- Adult neurogenesis may play a role in recovery

LECTURE THREE
LEARNING, MEMORY, AND AMNESIA

- Learning
○ The acquisition of knowledge or skills through experience
○ The storage process, the creation of memories
- Memory
○ The information that is stored (e.g. the memory of your grandmother)
○ The structure that stores the information (e.g. the strength of synapses in a
particular part of the brain)
- Amnesia
○ Memory loss

Types of Memory
- Short-term/working memory
○ Memory of things that just happened
○ Limited storage: 7 items (+/-2)
- --> consolidation
- Long-term
○ Memory of things that do not currently occupy your attention
○ They must be recalled to recognize
atory

role in
 ○ Limited storage: 7 items (+/-2)
- --> consolidation
- Long-term
○ Memory of things that do not currently occupy your attention
○ They must be recalled to recognize

Patient H.M
- Born Feb. 26 1926; died Dec. 02 2008
○ Henry Molaison
- Had intractable epilepsy that was resistant to the then available anticonvulsive
treatments
- Electroencephalogram indicated that the origin of the seizures was in the medial
temporal lobe (hippocampus)
- Surgical management considered and then undertaken
- Bilateral medial temporal lobectomy
- Medial temporal cortex
○ Hippocampus
○ Amygdala
○ Entorhinal cortex

○
 ○

- Outcome of H.M.'s surgery

○ Successful in reducing seizures
○ His overall IQ increased
○ Memory problems emerged
§ Severe anterograde amnesia
- What was spared after H.M.'s surgery?
○ Short term memory was relatively intact
§ Digit span test
§ Block tapping memory span test
○ Retrograde long term memory

Types of Amnesia
- Anterograde
○ Loss of the ability to create new memories after the event that caused the amn
○ Leading to a partial or complete inability to recall the recent past, while long-
memories from before the event remain intact
- Retrograde
○ Loss of memory access to events that occurred or information that was learne
before an injury or the onset of a disease

Digit Span Test

- Controls
○ First error around 7 digits
- H.M
○ First error at 6 digits
- Short term memory storage limited to 7 items (+/-2)
nesia
-term

ed
 ○ First error around 7 digits
- H.M
○ First error at 6 digits
- Short term memory storage limited to 7 items (+/-2)

Digit Span +1 Test

- Controls
○ Able to repeat up to 15 digits after 25 trials
- H.M able to repeat up to 7 digits after 25 trials

Block-Tapping Memory-Span Test

- Controls
○ Able to repeat a sequence of 5/6 blocks
- H.M
○ Able to repeat a sequence of 5 blocks
Block-Tapping Memory-Span Test
- Controls
○ Able to repeat a sequence of 5/6 blocks
- H.M
○ Able to repeat a sequence of 5 blocks

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What did we Learn from H.M.?
- Medial temporal lobe plays a critical role in memory
- Short-term memory and long-term memory are distinctly separated
○ H.M had problems with memory consolidation
- Memory may exist but may not be recalled
○ H.M exhibited a skill he did not know he had learned
○ Explicit vs. implicit memories
Explicit Memory
- Semantic memory is the memory for general facts and knowledge
- Episodic memory begins with the subject experiencing an event and ends with the
subject remembering or retrieving/recalling specific details of the event

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 -

How is Explicit Memory Stored in the Cortex?

- Fragmentation
○ Living vs. nonliving
○ Animals vs. plants
○ Lives in a particular environment
○ Unique physical features
○ Unique behaviour patterns
○ Emits a distinct set of sounds

Implicit Memory
- Knowledge that is expressed in performance without the subjects phenomenal
awareness that they possess it

-
Procedural Memories
- Responsible for skills and habits
- Autonomic and unconscious
○ Ride a bike
○ Drive a car
○ Tying shoes
○ Playing piano
○ Getting dressed
○ Typing

Neural Circuitry for Procedural Memories

- Basal ganglia - striatum
○ Habit formation
- Cerebellum
○ Store memories of sensorimotor skills

Patient J.K.
- Symptoms of Parkinson's disease starting in mid 70s
○ In Parkinson's the projections from the dopaminergic cells of the brainstem
(substantia nigra) to basal ganglia die
- Impaired implicit memory
○ Couldn’t remember how to turn the lights on
○ Couldn’t remember how to turn the radio on or how to use the TV remote
 ○ Couldn’t remember how to turn the lights on
○ Couldn’t remember how to turn the radio on or how to use the TV remote

Classical Conditioning
- A process in which an individual learns to associate a neutral stimulus (conditioned
stimulus CS) with a meaningful stimulus (unconditioned stimulus US) , gradually
reacting to the neutral stimulus with the same response as to the meaningful one

-
d
Operant Conditioning
- An association between a behaviour and a consequence for that behaviour
○ If the consequences are bad, there is a high chance that the actions will not be
repeated
○ If the consequences are good, however, the actions that led to it will become
probable

Types of Operant Conditioning

- Reinforcement
○ Positive
§ An appetitive stimulus that follows a particular behaviour and makes th
behaviour more frequent
○ Negative
§ The removal of a negative stimulus that follows a particular behaviour t
makes the behaviour more frequent
- Punishment
○ An aversive stimulus that follow a particular behaviour and this makes the
behaviour less frequent
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Habituation
- A decrease in the response to a benign stimulus when that stimulus is presented
repeatedly
○ Ex. Loud noises, smell of smoke

Mechanism of Habituation in Aplysia

- Touching Aplysia's siphon causes it to retract the gill
- Repeated touching causes Aplysia to habituate this

Sensitization
- Unpaired presentations of siphon touch and tail shock does not interfere with sipho
retraction
- Following siphon touch and tail shock pairing the siphon retracts for a longer perio

-
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od
 -

Synaptic Mechanisms of Learning and Memory

- Donald Hebb
○ Changes in synaptic efficiency are the basis for learning and memory
- Long-term potentiation (LTP)
○ Synapses are effectively made stronger by repeated stimulation
○ Firing of the presynaptic neuron is followed by the firing of the postsynaptic
neuron

LTP in the Hippocampus

- LTP occurs throughout the brain, but a high concentration of LTP occurs in the
hippocampus
- Within the hippocampus LTP is most commonly studies
○ The dentate gyrus granulate cell synapse
○ The CA3 pyramidal cell synapse
○ The CA1 pyramidal cell synapse
- A strong burst of electrical stimulation applied to the presynaptic neuron produces
increase in the amplitude of the excitatory postsynaptic potential in the postsynapti
 an
ic
 ○ The dentate gyrus granulate cell synapse
○ The CA3 pyramidal cell synapse
○ The CA1 pyramidal cell synapse
- A strong burst of electrical stimulation applied to the presynaptic neuron produces
increase in the amplitude of the excitatory postsynaptic potential in the postsynapti
neuron
- Repeated high frequency activity of the presynaptic neuron results in a long term
increase in the excitability of the postsynaptic neuron

LTP and Learning and Memory

- LTP can be elicited by low levels of stimulation that mimic normal neural activity
- LTP effects are most prominent in areas that have been implicated in learning and
memory (hippocampus)
- Behavioural conditioning can induce LTP like changes in the hippocampus
- Drugs that influence learning and memory have parallel effects on LTP
- Mutant mice with little hippocampal LTP have difficulty learning

Induction of LTP: Learning

- Induction of LTP dependents on:
○ Glutamate binding to NMDA receptor and inducing Ca2+ influx
○ Postsynaptic neuron most be partially depolarized
○ Co-occurrence of pre and postsynaptic activity

Maintenance and Expression of LTP

- Pre and postsynaptic changes in LTP are only seen in synapses where LTP was ind
- Protein synthesis (structural changes) underlies long-term changes

-
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LECTURE FOUR
HUNGER, EATING, AND HEALTH

Why do we Eat?
- Biological perspective
○ To obtain energy we need to support our everyday activities
○ To rebuild cells and manufacture various hormones, chemicals, and enzymes
○ Ultimately to promote survival
- Social and psychological perspective
○ To socialize
○ To celebrate
○ Form friendships, reaffirm relationships and commitments
○ Stress

Hunger and Satiety

- Two competing behavioural states
○ Hunger - desire for food
○ Satiety - sense of fullness (or satisfaction)
- Complex mechanisms that anticipate future requirements

Source of Energy
- Carbohydrates (starches and sugars)
○ Broken down into glucose, fructose, and galactose (monosaccharides)
○ Immediate source of energy - body will burn glucose first
○ Excess glucose can be stored in the liver and muscles
- Fats (meats, milk products, seeds/grains)
○ Broken down into fatty acids
○ Immediate source of energy
○ Excess can be stored in fat tissue
- Proteins (meats, beans, nuts, seeds)
○ Broken down into amino acids
○ May be turned into glucose, glycogen, or fat depending on needs
○ Used in the body for growth, repair, and energy

Energy Metabolism
- Three phases
○ Cephalic
s
 ○ May be turned into glucose, glycogen, or fat depending on needs
○ Used in the body for growth, repair, and energy

Energy Metabolism
- Three phases
○ Cephalic
§ Preparation to eat
○ Absorptive
§ Energy absorbed
○ Fasting
§ Withdrawing energy from reserves

Hormonal Control of Energy Balance - Insulin & Glucagon

- Insulin
○ Enables glucose to enter the cells (not in neurons)
○ Promotes the use of glucose as source of energy
○ Stimulates the production of glycogen, proteins, and fat
○ Stimulates the storage of glycogen, proteins, and fat
- Glucagon
 ○ Enables glucose to enter the cells (not in neurons)
○ Promotes the use of glucose as source of energy
○ Stimulates the production of glycogen, proteins, and fat
○ Stimulates the storage of glycogen, proteins, and fat
- Glucagon
○ Stimulates glycogen breakdown
○ Promotes the release of free fatty acids from adipose tissue
○ Stimulates the conversion of free acids to ketones

-
 -

Theory of Hunger: Set Point

- Hunger a consequence of an energy deficit
- Each individual has an optimal level of energy resources - set point
- Body seeks to return to this set point - homeostasis

Set Point Theory - What is Monitored?

- Glucostatic theory
○ Glucose levels determine when we eat
- Lipostatic theory
○ Fat stores determine how much we eat over long term
○ Explain how body weight tends to be constant over time
○ Long term regulation

Theory of Hunger: Positive-Incentive Perspective

- Anticipated pleasure
○ Animals driven to eat by the expected pleasure of eating
○ Expected pleasure = positive-incentive value (hedonic value)
- Craving
○ Eating (and the perception of hunger) is initiated by craving
○ Enables you to take advantage of good food (when it's available)
- Multiple factors influence hunger
 ○ Animals driven to eat by the expected pleasure of eating
○ Expected pleasure = positive-incentive value (hedonic value)
- Craving
○ Eating (and the perception of hunger) is initiated by craving
○ Enables you to take advantage of good food (when it's available)
- Multiple factors influence hunger
○ Flavour of the food
○ Knowledge about the food (learning)
○ Time since last meal, amount of food in gut, blood glucose

Factors that Determine WHAT we Eat

- Innate preferences
○ Evolutionarily driven
§ Naturally preferred
§ Sweet and fatty foods - high energy foods
§ Salty food - sodium rich
○ Naturally avoided
§ Bitter tastes - associated with toxins
- Learned taste preference and avoidance

○ Blue jays and monarch butterflies

○ Social transmission of food preference
- Nutritional content
○ Sodium deficiency induces innate drive to consume salty foods
○ Associating salt with flavours
○ Other vitamin and mineral deficiencies must be learned since taste is not obv
§ Thyamine (vitamin B1), depleted rats learn to choose a complete diet w
offered 2 choices - effect weakened when there were 10 choices
vious
when
 ○ Sodium deficiency induces innate drive to consume salty foods
○ Associating salt with flavours
○ Other vitamin and mineral deficiencies must be learned since taste is not obv
§ Thyamine (vitamin B1), depleted rats learn to choose a complete diet w
offered 2 choices - effect weakened when there were 10 choices

Factors that Determine WHEN we Eat

- Most mammals will eat many small meals throughout the day
- With modern lifestyle, we eat fewer large meals
○ Family, daily routines, schedules
- Premeal hunger
○ Eating a meal stresses the body: influx of fuel moves it away from homeostas
○ Signals for a meal (e.g. time of day, smells) evoke a cephalic stage
○ Insulin releases into blood --> decreases blood glucose

Factors that Determine How Much we Eat

- Satiety signals
○ Food in the gut
○ Glucose in the blood
- Appetizer effect
○ Small amount of food may increase hunger
- Serving size
○ The larger the serving, generally the more consumed
- Social influences
○ Even eats eat more in a group

- Sensory-specific satiety
○ More tastes available can lead to more eating - cafeteria diet
○ Satiety is sensory-specific
§ As you eat one type of food the positive incentive value of the food
decreases, but it offered a different food, you will eat again
vious
when

sis
○ Satiety is sensory-specific
§ As you eat one type of food the positive incentive value of the food
decreases, but it offered a different food, you will eat again
Hypothalamic Hunger and Satiety Centers
- A dual-center hypothesis proposed two centers in the hypothalamic
○ One for signaling satiety
§ Ventromedial hypothalamic (VMH)
Hypothalamic Hunger and Satiety Centers
- A dual-center hypothesis proposed two centers in the hypothalamic
○ One for signaling satiety
§ Ventromedial hypothalamic (VMH)
○ One for signaling hunger
§ Later hypothalamus (LH)

Ventromedial Hypothalamus - The Satiety Center

- Ventromedial hypothalamus lesions cause animals to eat excess (hyperphagia) and
become obese, suggesting the VMH could be a satiety center
- Two phases
○ Dynamic phase
§ Excessive eating, weight gain
○ Static phase
§ Body weight maintained over time

Problems with the VMH as the Satiety Center

- Damage limited to the VMH does not consistently increase eating
- Large VMH lesions also affect the ventral noradrenergic bundle that projects to the
paraventricular nuclei (PVN)
- Bilateral lesion of the ventral noradrenergic bundle produces hyperphagia and obes
well
- Bilateral lesion of the VMH increases blood insulin levels
○ Increases lipogenesis (production of fat)
○ Decreases lipolysis (breakdown of body fat)
§ Thus rats must consume more calories to meet demand

Lateral Hypothalamus - The Hunger Center

- Lateral hypothalamus (LH) lesions cause aphagia (refusal to eat), suggesting LH is
hunger center

Problems with the LH as the Hunger Center

- The aphagia (refusal to eat) may be due to lack of responsiveness to sensory input,
as food and water
- Possible motor disturbance
- However: specific lesion of LH cell bodies (sparing passing fibers) resulted in majo
loss of feeding with out loss of arousal and activity
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 loss of feeding with out loss of arousal and activity

Arcuate Nucleus of the Hypothalamus: The Appetite Center

- Neurons of the arcuate nucleus are sensitive to hunger and satiety signals
○ Leptin
○ Gherlin
○ Peptide YY3-36 (PYY3-36)
○ Insulin

Leptin
- Discovered in mice with a mutation in the obese (ob) gene
○ Ob/ob mice have more fat cells than wild type
Leptin
- Discovered in mice with a mutation in the obese (ob) gene
○ Ob/ob mice have more fat cells than wild type
○ Ob/ob mice become obese
§ Even when offered an unpalatable diet or when required to work hard to
obtain food
○ Ob/ob mice do not produce leptin
- Leptin is produced by fat cells (adipocytes)
○ Low levels of leptin increase hunger and decrease physical activity
○ High levels of leptin decrease hunger and increase physical activity
- Long term regulation of feeding behaviour
- Patient with congenital leptin deficiency shows a similar phenotype to ob/ob mice
○ Treatment with the leptin result in normalization of the body weight
○ Before treatment: 3 years old, 42 kg
○ After treatment: 7 years old, 32 kg

Ghrelin
- Produced by endocrine cells in the stomach
- Potent appetite stimulant
- Ghrelin levels rise during fasting
○ Trigger stomach contractions
- Ghrelin levels drop after a meal
- Obese subjects have lower baseline levels of ghrelin than lean subjects prior to eati
but levels do not drop after a meal

Peptide YY3-36 (PYY3-36)

- Produced by cells in the small and large intestine
- Potent appetite suppressant
○ PYY3-36 blood levels are low prior to eating
○ PYY3-36 levels rapidly raise during a meal
- Lower than average levels of PYY3-36 are associated with obesity
- Post meal increases of PYY3-36 in normal weight people are associated with feelin
satiety

Integration of the Hormonal Signals in the Hypothalamus

- Two sets of neurons in the arcuate
○ NPY/AgRP neurons - stimulate appetite
○ POMC/CART neurons - inhibit appetite
- Lateral hypothalamus
○ POMC/CART neurons --> release melanocortin in LH
○ NPY/AgRP neurons --> release AgRP in LH
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 - Two sets of neurons in the arcuate
○ NPY/AgRP neurons - stimulate appetite
○ POMC/CART neurons - inhibit appetite
- Lateral hypothalamus
○ POMC/CART neurons --> release melanocortin in LH
○ NPY/AgRP neurons --> release AgRP in LH
- Paraventricular nucleus
○ NPY/AgRP neurons --> release NPY in PVN

Why is There an Epidemic of Obesity?

- Evolution favoured individuals that
○ Preferred high calorie food
○ Ate to capacity
○ Stored as much energy as possible
- Modern lifestyle
○ Decline of home cooking
○ Larger portions, junk food
○ TV, internet, video games
○ Lack of physical activity
 ○ Decline of home cooking
○ Larger portions, junk food
○ TV, internet, video games
○ Lack of physical activity

Why do Some People Become Obese While Others Do Not?

- Energy input differences
○ Craving for high calorie foods
○ Cultural norms
○ Large cephalic phase response to sight and smell of food
- Energy output differences
○ Exercise
○ Basal metabolic rate
○ Diet induced thermogenesis
- Genetics interact with body energy input and output

Treatment of Obesity: Semaglutide

- Glucagon like peptide-1 (GLP-1) analogue
○ GLP-1 stimulates insulin and inhibits glucagon
§ Reducing glucose levels
○ Ozempic
- Bariatric surgery
○ Treatment indicated only for extreme obesity
○ Two different procedures mostly used

○
LECTURE FIVE
HORMONES AND SEX

What are Hormones?

- Hormone - chemical messenger produced by and released into the bloodstream fro
endocrine glands

- Act as chemical messengers in the body to regulate many body functions (e.g. hung
reproduction) and brain functions (e.g. emotions and mood)

Classes of Hormones
- Amino acid derivatives
○ Synthesized from a single amino acid (tyrosine and tryptophan)
○ E.g. epinephrine
- Peptides and proteins
○ Short and long chains of amino acids
○ E.g. adrenocorticotropic hormone (ACTH)
- Steroids
○ Synthesized from cholesterol (fat)
○ E.g. estradiol
om

ger,
Control of the Posterior Pituitary
- Paraventricular and supraoptic nuclei
○ Magnocellular neurons
§ Oxytocin
□ Contractions of uterus - parturition
□ Contraction of the mammillary glands - lactation
□ Social behaviour
§ Vasopressin or antidiuretic hormone (ADH)
□ Controls water balance - production of urine
□ Social behaviour
Testosterone Levels in Men
- Daily variations
○ Morning peak
○ Evening nadir

- Season variations
○ Summer peak
 - Season variations
○ Summer peak

HPG Axis
- Females
- Negative feedback

- Positive feedback
 - Positive feedback

- LH stimulates the production of progesterone and ovulation

- FSH stimulates the production of estradiol and follicular development

Rat Sexual Behaviour: Male

- Mount (a)
○ Forepaws clasped against females hindquarters
- Mount with intromission (b)
- Ejaculation (c)

®
Testosterone and Male Sexual Behaviour
- A castrated male rat loses interest in mating because testosterone is no longer prod
- Behaviour is restored with testosterone treatment - the activational effect; hormone
briefly activate behaviour

- Males with different sexual drive don’t show different levels of testosterone
- Testosterone replacement return them to their initial levels of copulation

Testosterone and Male Sexual Behaviour: Human

- Castration in humans leads to reduction in sexual interest and behaviour
duced
es
Testosterone and Male Sexual Behaviour: Human
- Castration in humans leads to reduction in sexual interest and behaviour
○ Effects are variable:
§ Asexual
§ Loss of ability to have erection but maintain sexual interest
§ Continue to copulate
- Level of male sexuality is not correlated with testosterone levels in healthy men
- Increasing healthy male testosterone levels does not increase sex drive

Neural Circuitry that Regulates Male Sexual Behaviour

- In male rats, the medial preoptic area (mPOA) coordinates copulatory behaviour
- mPOA sends axons to the ventral midbrain, then to the basal ganglia to coordinate
nurturing
- mPOA also sends axons through brainstem nuclei to the spinal cord to coordinate
reflexes of copulation

- Pheromones help coordinate reproductive activities

- The vomeronasal organ (VNO) - specialized receptor cells that detect pheromones
activate male arousal
- VNO information is sent to the accessory olfactory bulb, which then projects to the
medial amygdala, and in turn to the mPOA

Rat Sexual Behaviour: Female

- Estrous cycle - every 4-5 days
○ Four stages: diestrus I, diestrus II, proestrus, estrus
- can

e
 - VNO information is sent to the accessory olfactory bulb, which then projects to the
medial amygdala, and in turn to the mPOA

Rat Sexual Behaviour: Female

- Estrous cycle - every 4-5 days
○ Four stages: diestrus I, diestrus II, proestrus, estrus
- Receptive. Around ovulation - "behavioural estrus"
- Behaviour: lordosis

- Full solicitations
○ Female darts toward the male and runs or hops away
- Partial solicitations
○ Touchback: female pauses in front of the male
○ Runby: female runs past the male
- Interception

-
e
Estrogens and Progesterone and Female Sexual Behaviour
- Estrogens are important for female proceptive behaviour
- The subsequent production of progesterone increases proceptive behaviour and act
receptivity
- A female without ovaries will respond to a combination of estrogen and progestero
treatments

Testosterone and Female Sexual Behaviour:

- Estradiol's role on female sex drive is unclear
- Testosterone increases the proceptivity of ovariectomized and adrenalectomized fe
rhesus monkey
- Correlations are seen between sexual motivation and testosterone in healthy wome
- Testosterone has been found to rekindle sexual motivation in ovariectomized and
adrenalectomized women

Neural Circuitry that Regulates Female Sexual Behaviour

- In female rats, the ventromedial hypothalamus (VMH) is crucial for the lordosis
response through steroid actions
○ Estrogen increases dendritic trees of neurons in the VMH
○ Estrogen also stimulates production of progesterone receptors
- VMH sends axons to the periaqueductal gray in the midbrain, which projects to the
medullary reticular formation
- This in turn projects to the spinal cord via the reticulospinal tract
tivates

one

emale

en

e
 response through steroid actions
○ Estrogen increases dendritic trees of neurons in the VMH
○ Estrogen also stimulates production of progesterone receptors
- VMH sends axons to the periaqueductal gray in the midbrain, which projects to the
medullary reticular formation
- This in turn projects to the spinal cord via the reticulospinal tract
- As the male mounts, sensory information, via the spinal cord, and descending
information from the brain evoke lordosis

-
e