Dent Lectures Flashcards
Heredity and Behaviour
- selective breeding emphasizes certain traits, including physical and behavioural attributes.
- genetics play a significant role in the distinct characteristics of different breeds, shaping behaviours such as aggression, trainability, or herding instincts.
Greg Mendel Work
- demonstrated heredity through discrete traits in pea plants (round vs unwrinkled) -> at first, focus on discrete traits, hindered understanding complex behaviours, which are often influenced by multiple genes & environmental factors.
- researchers based ideas on Darwanian concepts.
Behaviour Genetics
- distribution of behaviour can vary by breed.
- within single breed, behaviours tend to cluster more narrowly.
- across breeds, behaviour sows a wider distribution, reflecting genetic diversity.
Francis Galton & Gaussian Distribution
- Galton introduced statistical tools (mean, STDEV, correlation to study heredity).
- Reversion to the mean: observed that offspring traits often regress toward the population mean.
- genetic factors - traits that correlate with parents.
- environment factors: introduce randomness, causing a pull toward the mean.
- did a Galton board experiment to demonstrate this.
Hereditary Genius (1869)
- Galton agreed
- first-degree relatives of a ‘genius’ are more likely to be geniuses due to shared genes.
- eugenics -> aiming to enhance the “human gene pool” through selective breeding.
- included ‘inferior race’/racial biased -> had controverses.
Analysis of Variance (ANOVA)
- analyze variance in distributions and partitioning it among different factors. (genetic vs environmental factors/contributions)
- in 1918, ronald fisher demonstrated that mendelian inheritance of discrete genes could explain continuous traits if phenotypes were additive. traits such as skin pigmentation result from additive effects of many genes.
Henry H. Goddard & IQ testing
- moron
- imbecile
- idiot
- objective measure of intelligence
- proposed that ‘feeble-mindedness’ was a mendelian trait - classified individuals based on their genotype.
- received criticism and eventually had to retract his idea.
Ellis Island Testing
Administered IQ tests to immigrants, concluding that many had “low intelligence” -> findings influenced restrictive immigration policies.
Army testing during WWI.
conducted intelligence tests on recruits, linking scored to nationality.
results used to justify immigration act of 1924, restricted immigration to northern europeans, halted immigration from asian countries (mirrored in canada).
Harmful policies - highlights dangers of pseudoscience and misuse of statistics.
Alpha army tests
written intelligence test administered to army recruits during WWI.
criticized for being culturally biased, required knowledge of english & specific culture references (agriculture terms)
Disadvantage to immigrants and non-native english speakers.
Army beta test
a nonverbal alternative test created for recruits with limited english proficiency.
used picture based task.
still biased, as it assumed familiarity with western culture objects and contexts.
Eugenics & forced sterilization
- prevent individuals deemed ‘feeble-minded’ or “unfit” from having children.
- women did it without their knowledge or consent.
- happened in Alberta and Germany (inspired by US policies)
JB Watson & Behaviourism
- focused on observable behaviour and behaviour modification.
- little albert experiment, to fear a white rabbit by pairing it with loud noises.
- radical behaviourism: watson claimed that he could mold any child into any professional role regardless of genetic background. this emphasized the whole of environment over heredity.
Competing Politico-Genetic Ideologies in 1930s
1) Soviet Union:
- rejected mendelian genetics in favour of Lysenkoism (which prioritized environment influence over heredity), led to agriculture failures due to unscientific policies.
2) Germany:
- adopted extreme eugenic policies under Nazi regime.
- sterilization and euthanasia of individuals deemed “unfit”
- expanded to include racial and social cleansing.
Eugenics after WWII
- eugenics: set of beliefs and practices that aim to improve the genetic quality of a human population.
- became stigmatized due to its association with nazi astrocities.
- term was avoided.
- the reason fro rejection was driven by political and moral shifts. Cold war and civil rights movements forced western nations to confront their own racist and eugenicist histories.
Explain the long struggle to find behavioural genes. Is correlation between parental & progeny behaviour necessary and sufficient to demonstrate a genetic contribution to behaviour?
- necessary but not sufficient
- a lack of correlation would rule out genetic contribution. But a contribution does not necessarily indicate genetic contribution, non-genetic factors could also explain the correlation.
- Ronald fisher proposed that continuously distributed phenotypes (behaviour) could be explained by action of discrete genes, aligning with ideas of Galton (evolution through selection) and Mendel (inheritance of traits).
First attempts at evidence.
1) Retrospective studies
2) search for mendelian behaviours
Better approaches:
1) model organisms.
2) experimental breeding.
can select for behaviour in mammals, experiment demonstrated that behaviour could bred into an animal population in relative short amount of time, supporting that behaviour has a genetic basis. (ex., fast rats make fast rats)
Candidate Genes
A candidate gene is a gene suspected to be linked to a specific trait, condition, or behavior based on its known biological function or how its mutation affects other traits. Instead of searching for a single gene responsible for a behavior, researchers study single-gene mutants with known effects to identify potential links between the gene and the behavior.
Pleiotropy
Single gene influencing multiple traits.
ex.) eye colour in fruit flies effecting behaviour.
Back-crossing to control genetic behaviour
- in genetics, back-crossing is used to minimize the genetic background variation between two strains while retaining the specific gene of interest.
- for example, when studying the effect of a dominant red-eye gene on behaviour, researchers back-cross the offspring to one parental strain (brown eye strain) repeatedly.
- each time, the red-eye trait (dominant gene) is selected for, but the genetic background of the offspring is made same as brown-eye strain. Ensures that the only remaining genetic difference is the one responsible for red eye colour.
- background eliminated = clearer comparison.
example with fruit flies:
- testing behavioural effects of a specific gene, involves measuring the time spent in a tunnel.
- suggest that red-eye gene does not have effect on time spent in the tunnel behaviour, instead the other genes in the genetic background are likely influencing the observed behaviour.
Geotaxis in Fruit Flies
- geotaxis can be influenced by genetic background.
- refers to the organisms response to gravity, (+) moving towards gravity, down) or (-) moving away, upwards.
Measurements of Heritability
Phenotype = Genotype + Environment
Var (P) = Var (G) + Var (E) + 2Cov (G,E)
Set Cov(G,E) = 0 (ie., a particular genotype is not more likely to be found in a particular environment)
h2 = Var (G)/ Var (P) = heritability (broad sense)
- more things affecting phenotype, more it spreads out, variance is a measure of how spread out the distribution is.
H2 is measure of relative effect of genetics, not absolute contribution to variance.
Can see if heritability is high cause of increased genetic variability, if environment has not changed.
Estimating heritability from putative isogenic lines
- genetically identical individuals
- Var (P) = 0
- Var (G) = 0
Therefore, variance in selected strain is Var (E)
So any variance between them must be Var (E) (by subtracting this, we can determine genetic variance)
Probably multigenic phototaxis, result reflective of additive genes.
Difference between monozygous (Mz) and dizygotic (DZ) twins is known.
- Mz (share all genes)
- Dz (share half genes)
- model based on variance genes: ACE model
A + C + E = 1
A = additive genetics
C = common environment
E = unique environment
E = 1 - Rmz (r = correlation coefficient)
Rmz = A + C
Rdz = 1/2 * A + C
H2 = 2(Rmz - Rdz) is the equation for the correlation of behaviours difference between Mz and Dz twins.
Mz = higher correlation and heritability.
Anything you can measure, can measure heritability.
- correlation is the flip side of variance.
- genetic techniques are now powerful enough to identify many genes of small effect.
- big peak = high correlation and strong linkage of gene & correlation linked to a particular disorder.
- can do the same thing with dog breeds.
Genes do contribute to behaviour. Need to understand how individual genes work - need mendelian. How can we partially get around this?
- can partly get around this by artificially introducing variation, combining mutagenesis and selection: phototaxis
- look for mutants that effect phototaxis.
behaviours affected by drosophila mutants
- phototaxis
- chemotaxis
- mating
-aggresion
-foraging
-circadian rhythm
-sleep
-associated learning
-geotaxis
-taste
-feeding - drug response
What are two examples of single genes determining behaviours?
(1) Sociality in worms.
(2) Foraging in flies.
What is the limitation of natural variation vs induced mutation?
- limitation is that only genes we identify are the ones that are diverse in that population.
- alternative is to create diversity where there is none, spontaneous mutation or induce mutation and look how that gene effects behaviour.
Explain example (2) Foraging in flies.
- fruit fly larvae must forage for food and have different foraging strategies.
- rovers vs sitters.
- rovers: distribute between two spots. rovers move much faster (when food is there).
- sitters: stay in one spot.
when there is no food, there is the same amount of activity.
both strategies co-exist in nature.
foraging strategy behaves as a Mandelian Trait.
The for gene can be mapped like any other gene (controls the difference between the two strategies)
- rover more dominant over sitter.
- if the gene is completely knocked out, it is lethal, making it easy to map since only viable alleles are observed.
- ‘For’ encodes a cGMP-dependent protein kinase (PKG). gene has exon and intron structures and is alternatively spliced.
- there is no difference in protein sequence between rover and sitter alleles, therefore the difference is likely due to the level of gene expression between the two.
- researchers created transgenic flies by attacking For gene to heat shock promoter. This promoter activates gene when flies are heated. Suggested that PKG activity influences whether the larvae exhibit rover or sitter foraging behaviour.
Which is better? Rover or Sitter?
- Darwinian model tells us it depends on advantage of being rover or sitter for the environmental factors (competitor)
- If low food and high competition, rover must be better.
- if high food and low competition, sitter must be better.
- frequency of each behaviour can fluctuate based on these factors, maintaining equilibrium in population.
Explain example (1) Social Behaviour in worms.
- social phenotype in C. elegans.
- social phenotypes is recessive and correlated with speed on food.
- both social and solitary phenotypes are found world-wide.
- NPR1 gene encodes a G-protein coupled neuropeptide receptor with two alleles defined by single amino acid changes.
- NPR1 is expressed in a subset of neurons.
- social = clump together (high food)
- solidarity = @ border (low food)
- look for gene mutations that cause social worms to become solitary.
- Gcy-35/Gcy-26 are oxygen sensing guanylate cyclase’s that act through cyclic nucleotide-gated ion channels (signalling proteins).
-> expressed in a bunch of neurons, inlcuding same ones as NPR. Signals to mmebrane channels, open, cation flow into neuron and cyclic nucleotide gated channel, depolarize neuron. Oxygen does this.
Worms have a preferred oxygen concentration. Explain.
- they are social cause they are trying to get away from oxygen, prefer lowest oxygen possible.
- can make worms solitary by manipulating 02 concentration, and making the concentration lower.
Where does NPR-1 act?
- expressing it solely in specific neurons (like URX and AQR) does not rescue social behaviour-suggesting NPR-1 acts on a broader set of neurons. exact neural mechanisms remain unclear.
- pheromones regulate social behaviour in C. elegans, with worms avoiding high pheromone concentrations to reduce crowding, indicating that their behaviour is driven by environmental cues rather than social awareness.
- naturally occurring polymorphisms in single genes can cause variations in behaviour, with subtly effects on the nervous system, leading to significant behavioural differences.
Chemotaxis
- the movement of an organism in response to chemical stimulus, either moving toward or away from the chemical.
- solidarity worms move away from high concentrations of oxygen and they move toward pheromones, which are chemicals excreted by other worms. (so they know which environment t go to - where less worms would be).
- olfaction is mediated by G-protein coupled olfactory responses.
Positive vs negative chemotaxis
Valence in chemotaxis refers to whether a chemical signal has a positive (attractive) or negative (repelling) effect on the organisms movement.
C. elegans determines valence at the level of sensory neurons.
- repulsion requires AWB sensoty neuron.
- ORD10 is the odorant receptor necessary and sufficient for detecting diacetyl-normally expressed in AWA sensory neuron.
- the decision to move towards or away from an odorant is determined by neurons that encode the valence of the chemical, AWB neuron is responsible for the repulsive response.
- odorant not originally repulsive but when expressed in AWB neuron, becomes repulsive,
- valence of odorant changes based on which neuron is expressing.
Labelled line for Valence (bacteria vs mouse)
Bacteria:
1) Odorant receptor neurons
- detect odorant
2) Interneurons (first layer)
- identify odorant
3) Interneurons (second layer)
- assign valence/execute motor program.
Mice:
1) Odorant receptor neurons
- detect odorant/assign valence
2) Interneurons (first layer)
- process/execute motor program.
Tracking in Chemotaxis
1) Run & Tumble (bacteria use this strategy)
- move straight (run) & periodically change direction (tumble)
- integrate signals overtime to detect changes in the gradient of the attractant.
- if they are moving towards high concentration, length run, decreasing tumble frequency, overtime, this bias in their random movement guides them to source of attractant.
- before tumbling, bacteria are less likely to move directly up the gradient, after tumbling, their turns are biased to increase the likelihood of moving up the gradient.
2) C elegans mostly follow the bacterial model, worm version of run and tumble is crawl reverse turning where reverse turns (pirouette) more likely when moving down the gradient.
- worms turns are biased rather than completely random, orientating them towards the gradient source more effectively.
Stereo-olfaction
So organisms use a spatial comparison, taking a “snapshot” of odour distribution across different sensors (left vs right) to determine direction.
- worms move through gradients to determine if the concentration is getting stronger or weaker.
- larvae move through gradients and also cast left or right to sense gradients.
- animals with bilateral symmetric sensors (humans) with 2 nostrils, can take a snapshot of the gradient by comparing left and right odorant concentration.
- rats use stereo-smelling to locate odor sources, associating left or right odorants with specific actions but when one nostril is blocked, side is absent, showing contralateral bias (favour the other to use) in response. This is the same for humans.
Fruit fly have bilaterally symmetric chemosensory organs.
- olfactory sensory neurons (OSN’s) express one or in rare cases two odorent receptors.
- a single odorant receptor is sufficient for chemotaxis.
- or83b is required for function of all other ORs.
- in or83b mutant, no chemotaxis to any odorant.
- or42a is sufficient for measurable chemotaxis to a single odorant.
- larvae use run and tumble strategy but with much better course of action.
- head casting (sniffling) explains ability to orient towards source of odorant.
AWC sensory neurons
- role is to detect attractive odorants and label their valence (+) or (-)
- microfluid chips - tiny channels control fluid flow at microscopic scale - allow testing of neuron responses to odorants.
- c. elegans nose is exposed to a flow of control fluid or fluid with odorant (fluorescently labeled to track)
- calcium sensitive GFP measures activity of AWC neurons in the presence or absense of odorants.
- odorant present - no activity.
- in C. elegans, removal, strong peak response, then gradual reduction, does not become strongly active in the presence of an attaractive odorant. it responds to removal or decrease.
- interneuron circuits:
AIY: activates in response to presence of odorants.
AIB: activates when reward.
process signals from AWC over minutes.
opposing roles in downstream neuron responses.
How does AWC influence pirouette behaviour?
- no odorant: increase pirouettes (freq turns)
- presence of odorant: reduced pirouettes
- odorant removal: pirouettes increase again.
All dependent on glutamate, knocking out glutamate neurotransmission eliminates change in pirouettes regardless of odorant.
Restoring glutamate signalling, specifically in AWC restores normal piroutte behaviours.
Motor Circuits
- only 2 layers of ineterneurons connecting sensory neurons to command interneurons that generate reversal behaviour (changing movement direction)
- this simplicity allows researchers to study the direct relationship between sensory and motor input.
- by selectively ablating (removal) specific interneurons, scientist can observe their absense affects the probability of reversal behaviour.
The Case of David Reimer
- infant boy lost penis by accident, creating dilema on how to raise him. Despite being chromosomal male, doctor suggestion raising him as a girl, to test ‘blank state’ theory (behaviour determined by upbringing & environment)
- early reports had success but when hit puberty, this stopped.
- he chose to live as a man showed importance of biological factors, including hormones and innate brain differences.
- case was not a true scientific experiment, lacked proper controls and clear evidence.
Pheromone experiments in C. elegans
- females (hermaphrodites) find certain pheromones repulsive, but males will find those attractive.
- use c. elegans are a model organism to test influence to sexually dimorphic behaviour.
FEM-3 protein
- determines sex in cell-autonomous manner.
- when expressed in nervous system (using pan neuronal promoter rab-3), FEM-3 can make females behave as males.
- limited anatomical differences, does not explain behavioural differences.
- will change specific response to pheromones to be like males.
What is the effect of CEM?
- Hermaphrodites & males both share taste neurons.
but males have CEM, if you get rid of this, male behaviour stays the same.
Courtship in Fruit Flies (CVA)
- olfactory visual cues: mechanosensory cues.
(orientation, tapping, wing extension, courtship song, licking, at tempted copulation, copulation/sperm transfer) - fruit flies more complicated, not just attractive or repulsed by pheromone.
- starts with smell like in C. elegans.
- males emit CVA, key odorant that informs flies who to court.
Essential between extinguishing mates & non mates.
Role of fruitless (fru) gene
- fru is a TF downstream of the sex-determination pathway.
- shows alternate splicing to produce male specific (fruM) and female specific transcripts.
- chaining behaviour in fruitless mutant flies, where males follow each other around in a repetitive manner.
- expressing only the female-specific spliced varient in males causes abnormal behaviour, such as chaining.
- male courtship behaviour requires FruM expression, while female-specific FruF expression reduces male courtship and increases male-male interactions.
Different behaviours like initiation of courtship, tapping and wing extension are controlled by specific neurons. each behaviour has its own distinct anatomical correlate.
Role of fruitless (fru) in song production.
- male flies produce a song using the thoracic ganglion, independent of the head.
- even in headless fly, activating fruitless neurons in thoracic ganglion can generate a normal male song.
- in females, activating fruitless neurons can induce song production, but it differs from males. by masculinizing fru neuron in females thoracic ganglion, the resulting song resembles a male song, demonstrated the critical role of fru in determining the sex-specific nature of song behaviour.
- mute males with wings removed cannot produce courtship songs but still attempt to court females.
- if only sine portion is played, females do not respond as they would to a full male song.
- females have neurons capable of producing song but don’t usually use them. but when masc, they use them and make similar courtship songs to males.
TrAP1 channel
- heat activated ion channel that opens when heated, causing neuron in it to depolarize and become active.
- by expressiing TrAP1 in specific neurons along with GFP for visuals, can see if activating these neurons is enough to trigger specific behaviour.
P2b neuron
- p2b neurons, which are involved in inducing courtship behavior in Drosophila melanogaster, are found in both males and females. However, their functionality differs:
- In males, p2b neurons are integrated into the courtship circuitry, and their activation leads to courtship behavior.
- In females, these neurons are present but are not connected to the circuits driving courtship, so they do not induce such behavior.
PC1 & PCD
- female specific neurons control specificity
- command interneurons respond to songs and pheromone
- pheromone enhances response of PC1 to song.
- mice also rely on pheromones.
- female resident (no pheromones), male intruder comes in, can’t smell him as a mate so she engages in odd behaviour/mounting, not expected.
VMH neurons
- sexually dimorphic subset of progesterone receptor-enhancing ventromedial hypothalamus neurons for female mating.
- progesterone hormone very important for female behaviour ‘love hormone’ mating
- humans respond to AND hormone (similar) - we secrete in our swear - if expose, human body temp. increases.
Putative pheromone activate male & female brains differently.
- females = androgen related compound.
- males = estrogen -related compoind.
- response to putative pheromone may correlate to sexual orientation.
- AND exposure is sufficient to activate VMH in heterosexual females.
- aggression is a successful strategy.
Crustacean posture
- function of antagonistic action of two neuromodulators (serotonin and octapamine)
- serotonin = promotes flexor muscle excitation and extensor inhibition, octamine does the opposite.
- this mechanism interplay induces submissive and dominant stances in crustaceans.
- manipulating serotonin levels alter the perception of social status in crayfish.
- when subordinate crayfish are treated with Sertotin, their behaviour shifts, potentially increasing aggression and challenging their established subordinate states relative to dominant crayfish.
- will increase probability of smaller crayfish winning fights.
- injection with octapamine decreases aggression reinforcing subordinate behaviour.
Dominance status is reflected in the response of synapses to serotonin.
- in isolated and dominant animals, serotonin enhances B ESPS, in subordinates, it inhibits.
- depends on social status & context.
- nervous system and status vary with social experience.
- dominance hierarchies are encoded in our brains.
When fruit flies are fighting, explain the brain circuits and how it is sexually dimorphic.
- males and females fight over food.
- wing threat, boxing, fencing.
- in males, there are dominance hieracheries (not in females), this reflects learned social roles. losers spend less time near resources and avoid aggression, solidifying their subordinate status.
- flies recognize a familiar opponent, familiar loser avoids fighting a known winner, while aggression persists with unfamiliar opponents, indicating that dominance is context dependent and influenced by prior interactions.
- the sex of the nervous system determines fighting style.
- males = lunges.
- females = head butts.
- if you masculinize the females, the fighting style will change.
- elav = panneuronal promoter
- tra = sex determining gene
- neurons that release Tachykinin-like peptide regulate aggression.
- neuropeptide promoter driving heat sensitive trpA cation channel. if activated, neurons that express that peptide get aggressive behaviour from those fruit flies.
Tachykinin-releasing neurons
- sexually dimorphic fruitless-expressing neurons (male)
- specific for aggression
- little effect on courtship - aggression specific.
What does aggression in male mice start with?
- olfaction
- vomeronasal olfactory gland neurons respond to urine (calcium imaging)
- olfactory information ends up in the ventromedial hypothalamus.
- a sexually dimorphic subset of progesterone receptor expressing VMH neurons necessary for male aggresion.
- different neurons in mouse ventromedial hypothalamus respond to males & females.
- pharamocogenetic inactivation of VMH inhibits aggression.
- activating VMH cells, optogenetically provokes aggression (light makes mouse attack, off - goes back to normal)
Dominance in mice
- dominance hierachies are important in aggression in social animals (mice)
- determine outcome of physical interactions, such as mouse pushing each other out of tube
- these hierachies are transitive, meaning if A defeats B, B defeats C, A will also defeat C.
mPFC medial prefrontal cortex
- AC (anterior cingulate)
- PL (prelimbic)
How can you alter dominance status in mice?
- changing strength of synapses can alter.
- higher ranking mice have stronger and larger amplitude excitatory potentials (ESPs) compared to lower ranking mice.
- can manipulate synapses and change the dominance hierachy, adding more channels, more response to glutamate, more response to ESPs in dominant mouse. can also make poison channel to decrease.
The neurobiology paradigm
- sensory input -> sensory neuron -> interneuron (metabolism) -> motorneuron -> behaviour output.
- worms increase feeding in response to food & serotonin - neuronal input cells tells us this information.
- C. elegans, like most organisms, exhibit satiety.
- insulin is important, if KO, will not see much effect on re-feeding.
C. elegans can follow two developmental paths
- in a bad environment, poor food, a lot of worms, will enter different environment phase called Dauer (metabolism) to adapt to surviving the bad times.
- they catch a ride with passing insects, get a ride to a place with better food and conditions.
- significant changes in response to environment cause to enter Dauer. (based on sensory input)
ASI neuron
prevents worms from entering Dauer state.
DAF-2
- DAF-2 insulin receptor in C. elegans, when activated by insulin, inhibits DAF-16, preventing worm from entering Dauer state.
- No insulin, DAF-2 inactive, DAF-16 remain active, triggering entry into Dauer.
- Insulin signalling regulates entry into Dauer.
- DAF-28, insulin-like pepide, plays role in regulating Dauer.
- DAF-2 regulates fat - independent of Dauer formation. When Daf-2 inhibits Daf-16, fat accumulation occurs independently of Dauer.
- usually Daf-16 normally promotes fat breakdown and energy expenditure.
- so you gain fat and go into dauer.
Tubby (Tub1)
- in worm
- regulates fat via neurons
Drosophilia metabolism
- drosophila regulates food metabolism through insulin, similar to humans.
- insulin releasing neurons in fly release insulin into hemolymph (blood) influencing metabolism, critical role in regulating glucose levels.
- drosophilia insulin-like peptides (Dilp) are released upon feeding.
How is insulin release regulated by fat?
- fat bodies, similar to adipose tissue in humans, send signals to the insulin-releasing neurons in brain.
- when fat bodies from well-fed flies are combined with brain in tube, promote insulin release.
- fat bodies from poorly fed flies, do not release insulin.
- must be some diffusible signal released by fat that tells brain to release insulin-like peptide.
Regulation of fat requires tubby & leptin pathway
- tubby acts in a hormone pathway in mammalian brain.
- obese mutant is a mutation in leptin.
- tubby expressed in brain.
- diabetic is a mutant in the leptin receptor.
- activation as the opposite effect on POMC (promote satiety release food intake) & AgRPINPY (promote hunger and increase food intake).
Effect of Melanocortin Signalling
- inhibits eating, downstream of POMC neurons.
- POMC neurons require Mcr4.
- AGRP neurons do not require Mcr4.
Mcr4r
- act in PVH (paraventricular hypothalamus) to regulate food intake but not energy consumption.
- PVH is downstream of arcuate nucleus, integrate signals related to hunger and satiety.
- does not regulate metabolism. if human has leptin mutation, can inject synthetic mutation.
Drosophilia mutants: per gene
- has 3 mutants:
long
short
arrhythmic - per changes periods / phases of circadian rhythms.
- if completely knock out this gene, activity is arhythmic.
- if per is effected, but not KO, there will still be effect on cycle periods.
How does per act on the brain?
- through a diffusible substance
- brain transplants identify the suprachiasmatic nucleus as the mammalian pacemaker.
- cycle period determined by genotype of SCN graft.
- cloning of per gene identified a TF that cycle.
- per is involved in a feedback loop that regulates its own transcription.
Negative feedback loops are fundamental feature of clocks. What is an example of this?
- clock-BMAL1 dimer is (+) regulator of per gene. when there is high enough concentration of per gene, it will cause negative feedback by inhibiting clock-BMAL1.
Per (P), Timeless (T), double time (DBT), clock (C), cycle (B), contribute to the clock.
- DBT stabilizes interaction between P & T (ensuring they bind) - once bound/stable, they translocate into the nucleus, interact with B & C, inhibit expression of genes that produce P & T, creating neg- feedback clock that regulates circadian clock.
- if they fail to interact, DBT degrades P & T.
What happens if you inject mouse SCN with TTX?
Arrhythmic activity
how do organisms adapt to a new time zone?
- entrainment of SCN by specialized retinal ganlgion neurons. (drives it)
- not driven by light sensitive rods & cones.
- maybe rods and cons limit rather than activate.
- RGSc (retinal ganglion cells) most important for circadian rhythms.
- circadian clock genes are expressed widely.
- drosophilia antenna have circadian sensitivity to odor (independent of the brain) - odorant sensitivity is autonomous to the cells.
Sleep as Behaviour
1) Wake
- sensation: vivid, externally generated.
-thought: logical progressive
-movement: continuous, voluntary
2) NREM
- sensation: dull/absent
-thought: logical
-movement: episodic, involuntary
3) REM
- sensation: vivid, internally generation
-thought: illogic, bizzare
-movement: commanded but inhibited
hallucinations
dreams
waking sleep pattern
rapid eye movement
What is the strongest determinant of sleep deprivation?
- sleep homeostasis - common to all organisms.
Why do we sleep?
energy conservation
avoid predators
repair stress
consolidate memory - role in learning - REM sleep = enhanced learning
place cells in hippocampus
- place cells fires when rats visit particular location within cage.
- novel patterns of awake neuron firing repeat during REM sleep.
- evidence for memory replay in humans.
the stress hypothesis
- suggests that sleep deprivation can be fatal, but it is difficult to test due to strong urge to sleep. to address this, researchers used a turntable with rates, where one rat is kept awake and one allowed to sleep, if awake rat falls asleep, risks falling into cold water. experiment shows that sleep deprivation leads to death in rats.
Brain is bathed in cerebrospinal fluid
- sleep deprivation in rats does not immediately reveal a clear cause of death, suggesting the damage might accumulate over time and effect the entire body.
- the fluid helps remove toxin produced by brain metabolism, during sleep, moves through brain, potentially helping in toxin clearance.
- sleep increases clearance of dye and B-amyloid from brain.
- something we do in out sleep, but not the reason we sleep.
Atonia in Canine Narcolepsy
- Narcolepsy causes individuals (or animals) to fall asleep inappropriately.
- Narcoleptic Dogs
Exhibit characteristics of REM sleep, such as complete loss of muscle tone (floppiness). - Triggers of Narcolepsy:
Excitement (e.g., cuddles, pets).
Food (a cataplexic stimulus).
Experiment with Food as a Trigger - Dogs love food, and food can be used to measure narcolepsy:
Place a line of treats and count how many are eaten before the dog falls asleep. - Narcolepsy Phenotype
—> Cataplexy: Loss of muscle tone triggered by excitement.
Sudden onset of sleep, especially REM sleep.
Intrusion of REM sleep into the waking state, leading to:
Hallucinations.
Muscle atonia (paralysis).
What is mutated in hereditary narcolepsy?
- oxerin/hypocretin peptide
- narcolepsy: a defect in sleep-wake transition (mouse orexin KO).
where are oxerin releasing neurons, where are their receptors?
- neurons in lateral hypothalamus
- receptors in brain stem (lower order parts of the brain)
orexin releasing neurons
- active when awake (must be active to maintain awake state)
- rate of firing occurs in response to stimuli.
- oxerigenic neurons intergrate information about glucose and fat.
- high [leptin], peptide hormone corresponds to greater fat stores.
- when no glucose, it is active.
- integrate information about multiple inputs including leptin and SCN.
what is sleep homeostasis mediated by?
Sleep homeostasis is mediated by adenosine, a chemical in the brain. Adenosine levels are low immediately after waking but gradually increase with prolonged waking. The more sleep-deprived you are, the higher the adenosine levels. Adenosine is constantly produced and removed at steady rates. However, if a drug blocks adenosine removal, it accumulates, leading to reduced wakefulness and increased time spent in slow-wave and REM sleep.
Adenosine and caffeine
Caffeine influences wakefulness by acting on adenosine receptors. Studies in rats show that injecting increasing amounts of caffeine results in more wakefulness throughout the day, with higher doses leading to more time spent awake. If the adenosine receptor is knocked out (KO), rats no longer respond to caffeine, confirming that caffeine’s effects rely on these receptors.
Adenosine plays a key role in sleep-wake regulation. As adenosine levels rise in the brain during the day, it promotes sleepiness by binding to its receptors, signaling the body to rest. Caffeine blocks these receptors, preventing adenosine from signaling sleepiness, making you feel more awake. Conversely, higher adenosine levels lead to stronger sleep pressure, increasing tiredness.
How can you turn off sleep in flies?
- activating neurons with trpA1
- kill flies
What differentiates language from communication?
- Language is characterized by arbitrary symbols. “nada” means “nothing” in Spanish but means “hope” in Serbian (semantic content).
- Language can lie.
- Language has rules of grammar (syntax). This allows combinatorial use of symbols to create many meaningful messages.
o “I see jane run.”
o “I see Jane walk.”
o “I see Dick walk.”
o “You see dick walk.”
Songbirds communicate but they do not use language.
The positional information in animal sounds is inherent to the sound’s generation and is not symbolic, meaning they cannot lie about their location (though some birds can misrepresent their identity). While songbirds can combine song elements in various ways, combinations outside their dialect do not convey meaningful information, as the semantic content remains unchanged.
Honeybee waggle dance
- dance conveys direction and distance, allows dead reckoning.
- angle of the dance relative to gravity indicates azimuth of the food relative to the sun.
- length of waggle part of the dance is proportional to distance to the food.
- bees receiving the message are not just using odor.
Brain damage that results in speech deficits correlates with specific brain regions
- broca’s area
- wernicke’s area
Theory of universal grammar (UG)
- Existing human languages exhibit a limited number of all the possible grammars.
o “Paolo eats the pear” conforms to UG.
o “Paolo eats the no pear” violates UG. - Humans learning languages don’t make mistakes corresponding to non-existent grammars.
Models to explain grammatical bias
- Two (extreme) models of gramma distribution.
- Evolution to equilibrium.
- Random Drift (founder effect)
- Both models probably apply to some degree.
- An attempt to deduce grammar bias based on rate of change.
Humans can learn non-UG languages
Humans can learn non-Universal Grammar (non-UG) languages, though Universal Grammar (UG) languages are easier to learn. In a study, German speakers were taught real Italian grammar (UG) and a fake, non-UG version of Italian. Similarly, they were taught regular and non-UG versions of Japanese. Results showed that participants learned UG languages more effectively, suggesting that our brains are more tuned to UG structures than non-UG ones.
What brain area is more important for real grammar?
Broca’s area
FOXP2
transcription factor expressed in brain
language areas with variant FOXP2 are impaired just thinking about verbs.
many organisms have FOXP2 in their brain but don’t have language.
it is involved in song-bird communication (increases in area X)
Human FOXP2 differs by two amino acids from all other primates but by only three amino acids from mice.
humanizing the mouse FOXP2 has subtle but significant effects.
