Neuroscience Flashcards
What is wrong with the nature vs nurture argument and what is its impact?
• False dichotomy between environments and genes:
o You cannot have any behaviour without the underlying biological mechanisms
o All biological mechanisms are in their present form due to the environment
• Very political concept-
o Theories of social class
Poor people are poor because they are unable not to be: innate features define social class
o Authorities and social development of poor communities
Why is it assumed that there is a biological basis to behaviour?
- Behaviour is often species specific
- Behaviour has an evolutionary history: Homologous behaviours are often shared by related species
- Behaviours change with developmental changes to the individual
- Behaviours change with biological changes
- Behaviours can run in families
Describe the development of evolution theory and the people involved in it
• Lyell- Used tectonic movements of plates and erosion to determine that the Earth was millions of years old
• Malthus- Described geometric population growth and interspecies competition as resources deplete
• Linnaeus- Organise kingdom in terms of organism similarity and differences- showed that organisms are similar to each other in systematic manner of ways
• Darwin and Wallace- Theory of evolution
o Common morphology between species is because of common descent and organisms can be categorised according to morphology
o Comparative neuroanatomy between species-brain parts developed according to evolution- shared homology
What is the concept of survival of the fittest?
• Survival of the fittest
o There are limited resources and there is competition for these resources
o Individuals who are best suited to their environment will survive and reproduce
o They will pass on their characteristics to their offspring (via inheritance)
What is fitness?
• Fitness, from an evolutionary point of view, is reproductive success
o Relative to direct competitors in the population
o The genetic contribution of an individual to the next generation’s gene pool relative to the average for the population, usually measured by the number of offspring or close kin that survive to reproductive age
What are the fundamental elements of evolutionary psychology?
o Brain causes behaviour
Breaks it down in 3 important categories-
• Function
o What is the goal to be achieved?
o Evolutionary psychology usually hypothesises about this first
• Algorithm
o What computations are used to achieve the goal?
• Implementation
o How are the computations physically implemented?
o Modularity
The mind is a large number of functionally specialised components
o Variation
Mental traits can change subtly from individual to individual within a population
o Inheritance
The mental traits that humans possess are the ones generated by genes selected over the course of human evolutionary history
o Selection
Some variants of mental traits provide an advantage to the individual in certain environments
Adaptative problems can only shape selection when the problem is one that has been repeatedly faced by the species in question and affect reproduction
Natural selection will retain genes that cause interactions with the environment tat lead to the reliable construction of the functional mechanisms that solve adaptive problems (ONLY ADAPTATIVE PROBLEMS)
o Development
Evolutionary approaches take selection to shape how genes interact with then environment by virtue of feedback loops between the genes in question and the structures that they cause to develop
What is artificial selection and is it the same as natural selection?
- Artificial selection often does NOT have the same results as natural selection
- Artificial selection is the intentional reproduction of individuals in a population that have desirable traits. In organisms that reproduce sexually, two adults that possess a desired trait — such as two parent plants that are tall — are bred together
What is the concept of psychobiology?
- Behaviour and other mental traits contribute to fitness
* For mental traits to be affected by evolutionary selection pressures, they must be inherited
What did Galton contribute to psychobiology/statistics and what movement was he one of the founders of? Who else supported this movement?
• Galton and Anthropometry
o Laboratory where he measured people’s physical attributes and performed psychometric testing and tried to see if physical attributes could predict mental ones
o Through demonstration of normal curve distribution with pinhole device with choice points and balls- the more choice points the balls had to go through, and the more balls there were, the more likely they would fall in the shape of a standard curve
o Theorised that human trait distribution also follows the normal curve
o Encouraged eugenics- thought that by breeding ‘superior’ humans with one another, would get perfect population
Pearson also encouraged eugenics and thought that ‘lower’ races could only become superior if the fittest were bred
Eugenics program all around the world during Nazi time, even in Victoria where wanted to sterilise those seen as inefficient such as homosexuals, slum dwellers, prostitutes, alcoholics and those with low IQ but this was abolished after the 2nd world war
Describe the Tryon experiment and what it determined
• Can breed cognitive traits genetically
• Tryon 1940-
o Rats trained to run through mazes to find food and number of errors done after several trials were recorded
o Rats with few errors were bred within their kind whilst rats with lots of errors were bred within their kind
o After several generations, saw two distinct curves- bright rats and dumb rats: the two populations had distinctly separated
Describe Kotrschal’s guppy experiment and what he found
• Guppy Kotrschal et al
o Bred big brained guppy fish together and small brained guppy fish together for several generations
o Found that big brain female (not male) fish were better at finding hidden food
o But found that big brained fish also had smaller number of offspring- outlines the difference in values between artificial selection for traits found culturally appropriate and appealing vs natural selection and fitness which requires for genes required for survival to be passed on to a large number of offspring
Is it always easy to see why a behaviour has evolved?
- It is easy to see how some behaviours increase fitness, such as aggression and competition for resources or intelligence and acquisition of resources, but not so much for others
- Just because a trait is useful for something, does not meant that that is exactly why the trait evolved
Be able to explain how at least one physiological trait could have been shaped into its present form via natural selection (hint: genetic polymorphisms)
Drug resistance by genetic polymorphisms-
• A gene can take multiple forms (alleles) that produce different versions of the same protein
• Different alleles can arise spontaneously via mutation
• Within a population, the mixture of alleles can change over time via natural selection:
o Alleles that confer a reproductive advantage will be represented in future generations more than alleles that do not
• For example, through selective pressure, mutations that are resistant to antibiotic may become more favourable to have and these will be passed on whilst non-resistant phenotypes will not live long enough to be passed on, making a resistant population
What is an adaptation?
o An inherited and reliably developing characteristic that came into existence as a feature of a species through natural selection because it helped to directly or indirectly facilitate reproduction during the period of its evolution
What are by-products?
o Traits that do not affect fitness but are linked to other adopted traits
What is noise/random effects in evolution?
o Random variation in a trait that does not affect fitness
What are exaptations?
o A feature, now useful to an organism, that did not arise as an adaptation for its present role but was subsequently co-opted for its current function
What is a spandrel?
o Features that now enhance fitness, but were not built by natural selection for their current role (when by-products become useful)
How do SSDRS increase fitness and what is an example
How do SSDRs increase fitness?
• Some behaviours have a very obvious relationship to fitness
o Confer a differential reproductive advantage in their niche
• Consider the species-specific defensive responses (SSDRs)
o Deer mice in Oregon
Took deer mice from pacific coast (where natural predators are stoats) and from the desert of Sierra in Oregon (where natural predators are snakes) and put them both in their respective and opposite territories. Found that deer mice placed in the opposite
What is a proximate explanation of behaviour?
Proximate (how):
An explanation in terms of immediate factors, relevant and potentially measurable in current time/structure
What is an ultimate explanation of behaviour?
An explanation in terms of the process and forces of evolution/function
What is a contemporary explanation of behaviour?
An explanation of the current form of a behaviour in terms of present-day
What is a chronicle explanation of behaviour?
An explanation of the current form of the behaviour in terms of a sequence
What are Tinbergens 4 explanations of causes of behaviour and what type are they?
Mechanism (causation) -Contemporary/Proximate Ontogeny (development) -Chronical/Proximate Adaptative value (function) -Contemporary/Ultimate Phylogency (evolution) -Chronical/Ultimate
What is Tinbergens’ causation explanation of behaviour?
Mechanism (causation):
Causal explanations in terms of what the behaviour is and how the behaviour is constructed. These explanations can include physical morphology, molecular mechanisms, other underlying biological factors, or external stimuli
What is Tinbergens’ development explanation of behaviour?
Ontogeny (development)
Developmental explanations for sequential changes across the lifespan of an individual. Often these explanations are concerned with the degree to which the behaviour can be changed through learning. Imprinting or issues of learning
What is Tinbergens’ function explanation of behaviour?
Adaptive value (function) Functional explanations regarding the utility of the current form of the behaviour with regard to increasing an organism’s lifetime reproductive success
What is Tinbergens’ evolution explanation of behaviour?
Phylogeny (evolution)
Evolutionary explanations that describe the history of the behaviour, such as which ancestor first possessed this trait, what was the antecedent to this behaviour, and what selective pressures in the past have shaped this behaviour
What are the 4 outcomes of interaction between animals on fitness and what do they involve?
Mutualism/reciprocity -Initiator benefit, recipient benefit Selfishness -Initiator benefit, recipient cost Altruism -Initiator cost, recipient benefit Spite -Initiator cost, recipient cost
How are altruistic genes able to survive?
• Your relatives are highly likely to share the same genes as you
• Altruistic act for person with an altruistic gene altruistic gene will survive (therefore indirect fitness- ensuring survival of gene through self-sacrifice)
• Assume there are genes for helpful behaviour (Hamilton, 1963)
o An altruistic act confers a cost to the donor, but it gives a benefit to the recipient
o However, if the recipient is related to the donor, then there is a chance that the genes for helpful behaviour will receive the benefit (but in another person)
When is altruism advantageous?
• Whilst there is a cost to the individual carrying copies of these genes, there is an advantage to the genes in the population if: relatedness x benefit > cost
o This might be if people are your kin
o This might be if you live in a community with a lot of other altruistic people
• Acts can appear altruistic in the short term, but if it is reciprocated later, both donor and recipient benefit in the long term
What does the indirect survival of altruism affect?
• This might affect:
o Maternal and paternal love
o Grandparent effect
Grandparents live to take care of offspring- selects for the genes of longevity
o Non-breeding relatives
Might explain homosexuality: non-breeding relatives live to take care of other relatives
What is the basis of trade?
o You give something that is of low value to you to someone who values it highly
o They give you something that you value highly but is of low value to them
What are the conditions of reciprocal altruism?
o There is a low cost to donor and high benefit to recipient
Trade a surplus for a deficiency
o Must have a reasonable chance of receiving reciprocation
Propinquity- need to be close to one another
o Must be able to delay immediate gratification
Humans are the best at this (Fehr and Rockenbach, 2004)
o Must be able to remember and punish cheaters
System works a lot better and everybody is fairer if you can identify and punish cheaters (Fehr and Rockenbach, 2004).
Describe Fehr and Rockenbach’s experiment on cheaters
• Pot of money at start and everyone has to contribute a little bit into the common good (which is doubled and distributed equally to everyone in experiment)
• People start to realise that they can get away with not giving as much to common good and then get a benefit
o Everyone starts to contribute less and less so people get less money overall
• Then allowed people to punish other people that don’t contribute as much as they should
• Everyone suddenly started to contribute to common good
Are human societies self-regulating?
Yes
What are most moral codes based on?
Most moral codes are based around issues of fairness or following authority
What are the 2 ways in which you can convince organisms to contribute to the common good?
• 2 ways in which you can get people to contribute to a common good
o Individuals identify cheaters, get angry and punish them
o Authority that controls behaviour of people in community
What is the Wason selection task and the result of this task?
• People were asked to analyse the Wason selection task in two different contexts:
o Describing the rules of a social contract
o Being asked to detect cheating
People are much more likely to solve the Wason selection test if it is presented as a test to detect intentional cheating
Much easier to do than abstract problem
o People may have modules to detect cheaters (specific for this type of problem)- built in parts of the brain specific to detecting blatant cheaters
Why and How has intelligence developed?
• Development of intelligence
o Need to have cognitive abilities to detect if someone’s cheating
o To remember who they are
o To maintain these relationships
• The demands of the social context drives the evolution of general problem-solving abilities in order to maximise personal fitness in this context (e.g. Tooby and Cosmides, 1992)
o Remembering interpersonal interactions
Expecting to get altruistic thing back if you gave
Episodic memory
o Transitive inference in hierarchical power relationships
o Deception
To be a good cheater, need intellectual skill
o Planning
o Arguing and getting your way
• Became smarter because others became smarter: need to get smarter than cheaters
What is the advantage of cohesive social groups?
• Cohesive social groups provide overall advantages to fitness to the members of the group
Describe Frans De Waal monkey study and what came from it
• Frans De Waal
o Monkey gives rock to experimenter to get reward
o When monkeys treated unfairly:
If give one grapes and one cucumber, create unfair situation
If monkey sees the other getting grapes, will refuse piece of cucumber given and will react poorly and refuse to eat the cucumber piece
• Human morals and ethics have evolved
o Biological basis in sense of fairness and ethics because sense is present to some degree in monkeys
• Biological basis to maintain fairness, equity and fair trade
What is evolutionary psychology falsely used to justify?
o Aggression Within communities/groups Between communities/groups Within sexes Between sexes o Inequality People are in the situation they’re in because of an innate quality: not because of social unfairness o Social Darwinism o Eugenics • Most people concentrate on the idea of competition driving evolution
What are different ways to increase fitness?
• Many ways to increase fitness
o Accidental adaptations
o Sexual selection
o Inclusive fitness and reciprocity
What is the basis of sexual selection?
• Sexual selection- depends on the advantage which certain individuals have over others of the same sex and species, in exclusive relation to reproduction, sometimes resulting in adaptations which are detrimental to survival itself. Two component processes:
o Same-sex competition (intrasexual competition)
To gain preferential access to mates through competition of the same sex
Mostly done by males
o Mate preferences (intersexual competition)
One gender might prefer specific features of the other sex
Mostly done by females
• A special case of natural selection-most important thing in evolutionary fitness
o Competition within a sex for mates
o The choice of with whom to mate
o Selection of a partner who will maximise the fitness of the offspring through:
Conferring healthy traits to offspring
Parental investment
What does sexual selection select for?
• Selection pressure on traits that reliably signal health and/or parental investment
o Physical traits signalling health, determining attractiveness
o Behavioural traits, signalling competitiveness and parental investment
How is human attractiveness determined and amplified?
• Attractiveness almost entirely determined by culture and time
o Fashion amplifies and exaggerates type of features
What are attractive features amongst every culture and what is each linked to?
o Facial symmetry-prefer symmetry (both men and women)
Linked with health advantages- better immune system
o Hip-waist ratio of about 0.6-0.65 for women, as well as fat on hips, breasts and buttocks
Linked with lower risk of cardiovascular diseases: signal for fitness and signal for nonpregnancy (Welborn, Dhaliwal and Bennett (2003))
o Shoulder-hip ratio for men
Signifies strength and athletic ability
o Clear skin
o Lustrous hair
o Full lips
o Good muscle tone
What are 3 middle level evolutionary theories?
o Theory of Reciprocal Altruism
o Theory of Parental Investment and Sexual Selection
o Theory of Parent-Offspring Conflict
What are 3 specific evolutionary hypotheses from the middle level evolutionary theory of Parental Investment and Sexual Selection?
- Hypothesis 1: In species where the sexes differ in parental investment, the higher investing sex will be more selective in choice of mating partners
- Hypothesis 2: Where males can and sometimes do contribute resources to offspring, females will select mates in part based on their ability and willingness to contribute resources
- Hypothesis 3: The sex that invests less parentally in offspring will be more competitive with each other for mating access to the high investing sex
What are the specific predictions derived from the hypothesis that Where males can and sometimes do contribute resources to offspring, females will select mates in part based on their ability and willingness to contribute resources
Prediction 1- Women have evolved preferences for men who are high in status
Prediction 2- Women have evolved preference for men who show cues indicating a willingness to invest in them and their offspring
Prediction 3- Women will divorce men who fail to contribute expected resources, or who divert those resources to other women and their children
Describe different behaviours in terms of the fitness advantage they confer
• Some behaviours act to increase fitness of the individual
o Aggression
o Adaptability and behavioural flexibility
• Some behaviours act to increase the fitness of the next generation
o Maternal love
o Jealousy
• Some behaviours act as reliable signals of fitness
o Music and dancing
• Some behaviours increase collective fitness
o Reciprocity
o Memory, self-control
Is there evidence for common descent of instinctive behaviours?
Yes
What is comparative cognition and the basis of it?
• To some extent, our mental abilities are determined by our biology
• All animals have evolved from common ancestors
• There should be preserved similarities between nervous systems
• But there should also be evolved differences
o Difference in nervous system may make differences
• Therefore, compare and contrast animals to make inferences about the relationship between CNS structure and function of cognition
Why and How do you measure intelligence in animals and what are the problems of doing this? What is a solution?
• Intelligence and problem-solving important determinants of fitness due to adaptability
• Strong selection pressure for intelligence in animals
• But how do you measure intelligence
o Gave various types of animals simple operant task to learn and saw how long it took them to solve it
But bees turned out to be much more adaptable than a human baby
• But would you get a human baby to solve the same problem as a bee?
• Species specific difference in ability to do things
Process not indicative of intelligence, but indicative of ability to do the specific task
o Gave various types of animals one task then another which is structurally similar but involves different types of things
Learning set- ability to transfer learning from a task to a new task which is similar
Start to see types of patterns of results that you’d expect
• Based on ability to transfer learning
What is the null hypothesis of intelligence?
o Comparative psychologists have wanted to understand evolution and nature of general intellectual capacity by exploring performance of non-human vertebrates in a variety of learning tasks, in the expectation of demonstrating superior intelligence in species more closely related to man
o It has however proved difficult to establish that any observed difference in performance is due to a difference in intellectual capacity rather than to a difference in contextual variables like perception or motivation
o Basically, is difference that we’re seeing because of intelligence, or some other factor based on the test which has nothing to do with intelligence or cognition?
Is the null hypothesis relevant within people?
• Null hypothesis basis of problem of intelligence testing between people
o Difference seen in performance because of intelligence ability or difference in ability to do the test?
Describe the problem of anthropomorphism based on the Horowitz experiment
o Put bowl of food in front of dogs
o Some dogs chained up so couldn’t get to bowls of food, and the other dogs were loose (and ate the bowls of food)
o Owners did not know if the dog had eaten bowl of food or not
Two rooms:
• One where dog ate the bowl of food
• The other where it didn’t
o Would scold the dog for eating bowl of food whether or not it has eaten bowl: dog would do ‘guilty look’ whether or not they had eaten bowl of food
o Guilty look not because did something wrong: instead submissive look in the face of anger
o Therefore ability to look at an animal and infer its mental state not very accurate: can misinterpret behaviour
What is the problem of cognition?
• To what extent is complex human-like behaviour simply the result of simple learning processes?
o Spontaneous problem solving vs learning, discrimination and generalisation
o A problem of inference
Inferring a mental state from behaviour
• To what extent is human problem solving any different?
o Complexity from simple processes
What is Morgan’s canon of interpretation?
- In no case may we interpret an action as the outcome of the exercise of a higher psychical faculty, if it can be interpreted as the outcome of the exercise of one which stands lower in the psychological scale
- The canon doesn’t exclude the interpretation of a particular activity in terms of the higher processes, if we already have independent evidence of the occurrence of these higher processes in the animal under observation
- If you can explain a behaviour through a simple process then don’t need a higher more complicated process for that sort of thinking
What was Thorndike’s view on animal intelligence?
Thorndike (1911)
• No such thing as insight in animal kingdom, but simple and dumb learning processes that produce apparently intelligent behaviour
What were Kohler’s views and experiments on intelligence?
• Behaviour cannot be reduced or explained by reducing it to simple mental processes- have to explain behaviour in terms of combined mental processes
o The sum of parts is different than its whole
• Kohler wanted to see if chimpanzees would get bananas suspended up in the air: solution dependent on environment around them and the chimpanzee
• Sultan experiment
o Tried to see if chimpanzees understood tool use and how to use it
o Put chimpanzee in cage with short stick with food out of reach of chimpanzee and short stick + chimpanzee but within reach of long stick + chimpanzee, as well as a large stick in separate cage that was out of reach of chimpanzee but within reach of short stick + chimpanzee
o Found that chimpanzee solves the puzzle (had sudden insight into whole of problem when eyes on solution) with knowledge of tools used in the past
What were Epstein’s experiments and views on human intelligence?
- Replicated Kohler’s banana in the air experiment
- Trained pigeon not to fly
- Shaped pigeon so that if it pecked banana, it got rewarded
- Then put block on floor with target and if pigeon pushed block over to target point, then got a reward
- Training behaviour independent, wanted to see if pigeon would combine the together to get both rewards
- Epstein argued that Kohler’s experiment worked because chimps had already played with tools, not because of sudden insight- and sum of parts were the whole because they had the parts together
Describe Weir et al’s crow experiment
- Tube with worms for bird at the bottom
- Bird given a straight piece of wire and has to figure out how to get basket out with worms using wire
- Crow made curved wire to solve problem despite no previous experience with puzzle, but had had experience with curved wires
- She did not show insight or purposeful tool manufacture due to the fact that in each first trial, she tried first with the straight wire without bending it, but did show evidence of reinforcement history
What is the role of tool practise in behaviour and problem solving?
• Intelligent behaviour in animals doesn’t arise spontaneously, but occurs with practice (some element of reinforcement but above instrumental learning)
• Use of tools only occurs if
o Opportunity to play
o Watch others
• But the use of the tools is entirely novel for each situation and is not a repetition of past (reinforced) behaviour
Are animals able to plan tool use? Describe Osvath’s experiment
- Can chimpanzees plan for the future
- Learnt to get rocks and throw rocks at people and liked to watch people run when he threw the rocks
- Removed the rocks yet he kept finding more rocks
- Through video surveillance, found that at night, was breaking pieces of concrete and storing them into hidden stash
- Future planning- making tool for future use
What is self-recognition?
• Have to have some idea as your body as yourself
Describe the marking test (Reiss and Marino) and who it works on?
• Put mirror in dolphin tank
• Get dolphin to come up and swim to the trainer in the tank
• The trainer will put a visible mark on the dolphin in an area that is hard to see, or just pretend to put a mark (to see if the dolphin, when it had a mark, was just checking itself out because of perceptual capture )
• Dolphin will look at mark, or try to find mark, on themselves
• Also passed by:
o Humans
o Primates
—-Initially not recognise themselves but will recognise themselves after a bit
—-Use the mirror to look at bits of itself -to reference and observe themselves
o Elephants
• Theory of own self- first step in theory of mind
What is an intentional stance and an example of this regarding altruism?
• A person intends to do something
• Need to find what the goal of that behaviour may be
• To do help, need to understand that the person needs help and what it wants
• Warneken, Tomasello
o Altruism in children and chimpanzees
Prosocial behaviour in children- requires understanding of what the person needs and wants by looking at person’s behaviours
Prosocial behaviour in young chimps as well- chimp helped person pick up sponge (with no verbal cues)
What is the theory of mind and how was it tested nonverbally by Call and Tomasello?
- Another individual wants/believes something different than the self
- Human theory of mind is closely tied to language
• Nonverbal false belief task- Call and Tomasello
o Performance of children and great apes
Person 1 hides banana in a box and leaves the room (doesn’t know that banana has been switched), another person switches the banana in another box. Asked to indicate where person 1 will think the banana is
In children, kicks in at 5 years old (whether verbal or non-verbal)
• Autism- fail false belief but pass true belief and control task
• Specific language impairment- completely fine with every task
In great apes, pass the false-belief test
Why is theory of mind evolutionary essential?
- Need theory of mind for reciprocal altruism and reciprocal trade (where can figure out what other individual needs)
- Need theory of mind for deception and cheating- can see what people know and exploit what the other person does not know
How did Darwin influence psychology?
• Continuity between species
o Comparative psychology
Allows us different perspectives on intelligence that only studying people doesn’t allow us to do
• Variation of intelligence seen in people is extremely small
• Instinctive behaviours
o Major influence on James, Freud and ethology
• Developmental theory
o Progress through stages of development
• Morals
o Adaptive significance of behaviour rather than theological doctrine
• Individual differences
o Study of the variation between individuals
What are genes, what is their purpose and how are they passed on?
• Genes are locations on chromosomes
o Basic unit of heredity
o Encode functional RNA and proteins
o Transmission of genes to offspring is the basic process of inheritance
Chromosomes replicated in germ cells and passed on to next generation
o Locations on chromosomes are certain genes important for certain characteristics
Are genes the same in everyone?
• Genes can vary between and within people
o Genes in same location, but version of gene may be different from person to person
What is homozygous?
o Homozygous-one version of gene on both chromosomes
What is heterozygous?
o Heterozygous- one chromosome has one gene, the other has other gene version
If one dominant over the other, phenotype will express dominant gene
What is the heritability quotient of a trait and how does it work?
• Heritability is the component of the variance of the phenotype that can be explained by heritable factors
o Heritability increases when genetics are contributing more variation or because non-genetic factors are contributing less variation: what matters is the relative contribution
o Heritability is specific to a particular population in a particular environment
o Heritability of a trait should not be interpreted as a measure of the extent to which said trait is genetically determined in an individual
o Assumes no epigenetic interference
• Heritability quotient- H^2
o H^2= V(g)/V(p)
What are identical-monozygotic twins?
o Identical-monozygotic twins
Come from same sperm and egg and shared placenta, which then splits into 2 individuals
What are fraternal-dizygotic twins?
o Fraternal- different to each other -dizygotic twins
Two separate sperms and eggs at time of fertilisation
Separate placentas- two different individuals born at the same time
How is heritability tested?
• Test heritability through twin studies
• Heritably estimates done by looking at similarity of traits between these types of twins
• Calculate the correlation between siblings on some phenotype
o Monozygotic twins raised together
o Dizygotic twins raised together
o Monozygotic twins raised apart
o Adopted siblings
• Differences in these correlations can be used to estimate V(g) and V(e)
What are assumptions made to test heritability through twin studies?
• It is assumed that P=A+C+E=1
o A-variance from additive genetic components
o C-variance from a common family environment
o E-variance from a unique personal environment
• Correlation of monozygotic twins=A+C=1-E
• Correlation of dizygotic twins=0.5A+C
• Correlation between monozygotic twins raised apart=A
• Correlation of adopted siblings=C
Describe the minnesota study (Bouchard et.al.)
• Bouchard et.al
o Studied mental and physical traits of identical twins reared together as well as dizygotic twins reared apart to assess the relative contributions of genetic and environmental factors on the physical, mental and personality traits that creates human individuality
o Found different of ratios of similarities between the twins
o Correlation (monozygotic twins reared apart)/correlation (monozygotic twins reared together)= A/(A+C)
Physical traits- very similar, mental traits- there is strong genetic component and environmental contribution
o Bouchard estimated the heritability of a personality to be about 40%
o Bouchard estimated the heritability of intelligence to be around 70%
o But because individuals are likely to seek outlets for their innate tendencies regardless of what environment they are reared in, one will never be able t provide a definite or undisputed estimate of heritability for any given trait
What is the phenotype?
• Measurable expression of a trait is the phenotype
o Phenotype- physical measurement that trait
What is phenotypic variance the sum of?
• Phenotypic variance (Vp) = Vg +Ve+ Vge
o Vg- genetic variance
Additive components (Va) + dominance components (Vd) + gene interaction effects (epistasis-some genes modulate expression of other genes) (Vi)
o Ve- environmental variance
Common environmental (Vc)+ unique environment (Ve)
o Vge- gene-environment interactions
How is quantitative analysis of traits done?
• Studying ‘genetic architecture’
o Characterise quantitatively a behavioural phenotype in a given population/strand derived from nature or by artificial selection
o Examine the changes in phenotype in sets of progeny from test crosses between different populations
o Infer statistically the number of genes responsible and their interactions
o Look at entire genome of individuals code sequence of individual and look to see if there are variations of phenotype relations with that of the entire gene
After breeding bright and dull rats into two specific traits, what did Tryon (1940) do?
• Tryon (1940)-continuation
o Wanted to see if there was a single gene responsible for intelligence
o Got dull rats and bright rats and bred them together(F1)
o Got animals from (F1) and bred them together
o Bright strain and dull strain did not reemerge- therefore brightness and dullness not a single gene and is a polygenetic trait (associated with many genes)
How is quantiative trait loci mapped?
• Quantitative trait loci are mapped by identifying which molecules markers (such as SNPs) correlate with an observed trait
• Then sequence the actual gene that cause the trait variation
• We can identify sections of the chromosome that are linked to the trait statistically:
o We know the locations of some variable ‘markers’ on the chromosomes
o We can calculate whether the changes in the expression of a trait is linked with polymorphisms at these sections of the DNA
Single nucleotide polymorphisms
• Some specific nucleotide positions in a species’ genome are highly variable
• By mapping the sequence of DNA in many individuals, the locations of high inter-individual variance can be mapped across the genome
• This variance can then be correlated with variance in a trait
Can make a manhattan plot- probability that variation in that part of the genome correlates with variation of a trait
• Then check is specific genes in that region are driving variation
How are single gene approaches to studying psychological traits conducted?
- Studying the contribution of likely candidates for a phenotype based on what is known about their neurobiological bases- what sort of biological mechanisms that could underly a trait
- Got sample and scanned the genome see what gene is there psychological tests to determine prediction of performance in specific task
What is a potential marker for alcoholism?
o Alcohol dehydrogenase as a marker for alcoholism
Describe Goldberg and Weinberg’s study on COMT
Goldberg and Weinberg
o Tested difference in working memory
Found association between COMT polymorphisms and prefrontally-based executive functions and neurophysiology
Describe COMT
o Catecholamine-O-Methyltransferase (COMT), enzyme that helps break down neurotransmitters as a marker for cognition
• There are two different types of COMT gene-
o High activity and thermostable- Valine amino acid variant
o Low activity and thermolabile- Methionine amino acid variant
What are two ways of conducting single gene approaches?
• Techniques
o Testing people with polymorphisms of the gene
o Genetically modified animals
Describe a leptin single gene study made with mice
Mice-genome manipulated so that leptin has been disrupted so that animal has no longer produced it
• Mouse that has lost leptin gene has lost ability to stop eating
• Leptin is important for its regulation of appetite
Easily done with CRISPR- which inserts new genes in animals to see if it produces change of behaviour
What are problems with twin studies?
• Twins as representative of the population
o Are twins treated differently or similarly as other kids? Are they appropriate as a population sample?
• Contextual nature of the results
o Very had to replicate results from lab to lab or using different measures of the same trait
o Laboratory specific effect-suggests estimate types are not very precise
• Mis-estimation of differences in V(g) and V(e)
o Miss out dominance and interaction effects (ignoring these genetic contributions), therefore may overestimate A
o Monozygotic twins raised apart- assumed that the variation between these is only determined by their genetic component but could be an underestimation of a common environment for these twins (kC)
• No estimation of V(ge)
Describe the Jack Yufe and Oskar Stohr case study
• Case study: Jack Yufe, Oskar Stohr
o Born in Jamaica
o Oscar was taken to Germany and put into the Hitler youth (catholic) whilst Jack was brought up Jewish
o When came together for Minnesota twin study, they hated each other because of huge variation in political views but noticed they had a lot of similarities
Breaking tension in room by sneezing
What are problems of single gene analysis?
• Ignores the important contribution of background genotype to phenotype
o Effects of genetic manipulation might vary from strain to strain
o Effects of a gene might depend on other genes being present of absent (epistasis)
• Redundancy and pleiotropy in mechanisms obscure the ability to draw relations between genes and traits
• Ignores roles for adaptation and developmental effects
o The apparent changes in phenotype might not be due to the direct effect of the gene, but due to compensatory changes during development
Animal as it develops adapts to the fact that it doesn’t have that gene- gene changes developmental trajectory in a way that is unpredictable
• CRISPR twins- Modification China
o Used CRISPR to delete CCR5 receptor for girl to prevent her from catching HIV
o Girl has altered psychological profile due to downstream effects
What is redundancy?
o Redundancy- more than one gene produces the same effect, so knocking out a gene might have no visible effect on a trait
Lots of redundancy in biological systems
What is pleiotropy?
o Pleiotropy- a single gene might contribute to more than one trait
What is the problem with quantitative analysis?
• Results do not identify individual genes:
o Necessity for discovering candidate genes at the sections of DNA that are highly associated with the trait
o Follows the effects of multiple genes with small contributions to phenotypes
• Necessity for large pedigrees and cross-mating makes human studies unlikely
o Except Iceland pedigree
• Need large samples
-High risk of false positives
What are problems in behavioural genetics?
• Lack of evidence for any complex psychological trait that is determined by a single gene
o Also a lack of consistency between polygenic studies
Different sets of data can express different things
• What does a genetic marker actually mean
o Is it predictive or useful, or is it just a basis for discrimination
• Vagueness in incorporating a mechanistic role for the gene in the phenotype
• Often a definitional or measurement problem with psychological traits
o Measurements are poorly verified
• Behavioural phenotypes tend to be more polygenic than other traits
What is the purpose of a gene?
• A gene
o Makes other genes (replication during cellular division)
o Makes RNA (transcription)
o Part of DNA sequence (with promoter and enhancer) which produces pre-mRNA which gets edited (by splicing and other stuff) into mRNA which gets translated into a protein
What is the purpose of RNA?
• RNA
o Can be used to regulate genes (go back into nucleus and regulate other genes)
o Can have enzymatic activity (RNA based enzymes)
o Can make protein (translation)
What is the purpose of proteins?
• Proteins
o Regulate genes (go back into nucleus)
o Have enzymatic activity
o Have a structural role (can form cytoskeletons)
o Are used in signalling (released within organelles in cell or go to other cells)
What are 4 ways in which environments can modulate genetic output?
- Regulate at the level of transcription
Determine whether or not gene is read into mRNA - Regulate at level of translation
Determine whether or not mRNA translated into a protein - Post translation control
Regulation of protein activity
• Post translational modification of proteins can change their structure and hence function
• Change their efficiency levels - Natural selection of genotype
How is gene expression measured?
• Gene expression:
o Measure mRNA (PCR, in situ hybridisation)
How is protein translation measured?
• Protein translation
o Measures concentration of proteins (ELISA, Western blot, etc)
How is post-translational modification measured?
• Post-translational modification
o Measuring protein variants and isoforms (ELISA, Western Blot, …)
Why is there an advantage to measuring genetic activity?
• Can build map in brain/body as to whether or not there is a gene and whether this gene is active or not (dynamic activity) in an individual at different epochs in person’s life
What are epigenetic mechanms affected by?
• Epigenetic mechanisms are affected by these factors and processes: o Development o Environmental chemicals o Drugs/pharmaceuticals o Aging o Diet
What is the purpose of DNA methylation?
• DNA methylation
o Methyl groups (an epigenetic factor found in some dietary sources) can tag DNA and repress genes
What is the purpose of histone modification?
o To read off gene bound to histone, have to slightly unwind genes (needs to be a little bit of looseness)
o The binding of epigenetic factors (can be acetylated) to histone tails alters the extent to which DNA is wrapped around histones and the availability of genes in the DNA to be activated
o Acetylation makes it easier to read, methylation makes gene harder to read
What are histones?
o Histones are proteins around which DNA can wind for compaction and gene regulation
Describe the implications on environmental contributions of Crab et al.’s study
• Crabbe et al.
o Range of mice different strains raised in different labs and set up 3 different labs in US
o Trained them how to run behavioural tests- tried to get everything reliable and consistent in the different
o Mice- open arena-give mice substance- try to see how much they move around arena
o Different results based on where the tests were run
o Subtle effects that are hard to control against that produce changes in behaviour for genetically similar animals (environmental effects)
What are the 4 models of gene-environment interactions?
- Genetic and environmental effects might be independent but additive
a. Phenotypic variation =A+C+E - Some environmental effects might only be seen under certain genetic conditions
- Some genetic effects might only be seen under certain environments
a. An individual may have a genetic predisposition to antisocial behaviour, but not demonstrate this trait unless he or she experiences abuse or neglect in childhood
b. A genetic predisposition may be overcome by protective environmental circumstances
i. For example, individuals with a predisposing to alcohol abuse may live in a culture that forbids the consumption of alcohol - Some genetic effects might influence the environment to which an individual is exposed
a. Alcoholics tend to create an environment that facilitates drinking
i. Alcoholics tend to self-associate with other alcoholics
ii. They have a lot of alcohol in the house
iii. Importantly, children of alcoholics tend to grow up in environments rich in alcohol, increasing their chances of being exposed to alcohol
b. Create a risky environment for themselves and their genetic predispositions are shown
Describe Cooper and Zubek’s 1958 study using Tryon’s rats
a. Cooper and Zubek-1958
i. Got Tryon’s bright and dull rats to see if environment affected them
ii. Raised rats in enriched environmental conditions and restricted environmental conditions
1. Normal environment: 4-8 mice, large tubs, little colony
2. Enriched environment: Large enclosure, running wheels, social colonies, ropes to climb…
3. Restricted environment: social isolation
iii. Bright strain of rats in enriched environment didn’t show any benefit but dull strain of rats did (genetic background of rats determined whether enriched environment had any effects)
1. Saturation effect for bright rats
iv. When restrict environment, didn’t do much to dull strain of rats but stunted growth of bright rats (genetic background of rats determined whether restricted environment had any effects)
Describe Corder et al.’s 1993 study on Alzheimer’s disease in women
i. People carry different versions of this gene:
1. Alleles are ε2, ε3 and ε4
ii. People who contract Alzheimer’s disease at a younger age are far more likely to carry the ε4 allele than is normal in the population
1. Relative risk
iii. Women taking estrogen (hormone therapy) to minimise AD diagnosis are benefited only if they don’t have ε4
iv. Head injury isn’t linked to AD unless there’s also ε4
v. Genetic link between the effect of environment to development of cognitive aspect
Where did the field of epigenetics come from?
• Came from cancer biology
o Found that DNA that suppressed tumors was chemically modified (methylated) in cells that were cancerous compared to those who weren’t
What is an example of epigenetics with locusts and grasshoppers?
• Under condition of food stress, serotonin production changes in nervous system of grasshoppers so that genes get modified, which has hormonal effect which changes grasshopper colouration and encourages aggressive behaviour. They become locusts.
o Locusts and grasshoppers same species- one is just of different genetic activity to the other
What is epigenetics?
• Epigenetics refers to the changes to the functional genotype of the cell
o DNA code is not altered but chemically modified so transcribed and translated in different ways then before
It is chemically modified so that some parts of it become less (or more) likely to be expressed
o This can produce long-lasting and even permanent changes in the phenotype
• Epigenetic switches and markers (which are chemicals on DNA) can help switch on or off the expression of particular genes
• Epigenetic signals from the environment can be passed on from one generation to the next
• Bidirectional Manners of epigenetic regulation
o Physically blocks access to genes by altering histones (winding them more tightly/ unwinding them)
o DNA methylation- involves the addition of a methyl group to particular bases in the DNA sequence
Describe observations made in the netherlands after WWII involving epigenetics
- Nazis occupied the Netherlands- as allies pushed them out, destroyed all ports and bridges in Holland
- After, winter followed: people who lived near river and coastline could get food delivered to them but couldn’t bring it to interior because of lack of bridges
- Huge famine resulted-a lot of children starved
- Found that children in the interior of the Netherlands tended to develop mental health disorders as they got older compared to people who lived near the rivers
- Children in interior have higher levels of methylation on particular genes compared to those who lived on the coast
Describe the Garrett-Bakelman NASA study
• One twin was sent to space for 365 days, the other stayed on the ground
• NASA got the two to go through pre-flight test, during flight and postflight to test markers
o Biochemical
o Cognitive
o Epigenomics
o Gene expression
o Immune
o Metabolomics
o Microbiome
o Proteomics
o Physiology
o Telomeres
• Twin that was up in air showed changes to epigenetic markers and changes to cognitive markers postflight
o Showed massive change in ability to do processing speed tests and attentional tests
What is the problem with inheritance
• Problems with trying to find ‘genes for a behaviour’
o The genetic contribution to a behaviour might be indirect
o It’s not necessarily the type of genes you hold that’s important (the genotype), it’s whether the genes are expressed (the functional genotype)
o The functional genotype is heavily affected by environment
• Inherited variations in phenotypes are heavily determined by subtle variations in common environments that are stable across generations
Why are both nature and nurture involved in behaviour?
- Genes rarely program behaviour
- They might provide a disposition to behave
- This disposition can then be reinforced or eliminated by the environment across development
- So while there may be a genetic component to behaviour, it requires an enabling environment to be expressed
- Expression of behaviour is influenced by culture- have fundamental need but expression is expressed through different types of cultures
- Behaviour itself can be quite flexible but what is occurring at the biological level might be fundamental to the simple motivational and emotional processes that motivate the type of learning that you have from your culture
Describe Francis et al’s study on maternal rats (first part until first behavioural findings)
o Maternal behaviour of rats
Protect their pups in specific kind of way
• Arched back nursing
o Presenting their tits to the pups to allow them to drink
• If pups get distressed, the mum licks and grooms
o High licking/grooming mums (H) vs low licking/grooming mums (L)
Adopt out all the offspring of H and L mums at brith
Give half of each group to H or L mums
Gives 4 groups
• H-H, H-L, L-H, L-L
And undisturbed (C ) or disturbed (w) controls
• H/C, L/C, H/w, L/w
o Is maternity heritable?
o Examine three things
What is the rate of licking or grooming of the L or H mums to their adopted or natural offspring?
Do the offspring show changes in tests of anxiety as adults?
Do the offspring change the type of maternal care they show their own offspring when they breed
o Those who had high maternal care mums and were raised in high maternal care families also displayed high maternal care to their pups
o Those who had low maternal care mums and were raised in low maternal care families also displayed low maternal care to their pups
o Those who had high maternal care mums and were raised in a low maternal care environment gave low maternal care to their pups
o Those who had low maternal care mums and were raised in high maternal care environment gave high maternal care to their pups
In Francis’ maternity study, what was the difference in pups anxiety levels?
Rats raised by H mums are less anxious when adults
• Found by placing pup adults in an open environment
What happening when young changed emotional responses for rest of life
• But not a genetic thing- imprinted by environment
In Francis’ maternity study what was the mechanism for different anxiety levels in the pups and how was this found?
Wanted to see what was happening in the brain of these adults
• Got those who came from high maternal care mums which were given no extra care with stroking paintbrushes
• Got those who came from high maternal care mums who were given extra care with stroking paintbrushes
• Got those who came from low maternal care mums who were given no extra care with stroking handbrushes
• Got those who came from low maternal care mums who were given extra care with stroking handbrushes
Did this through in situ hybridisation
• High levels of glucocorticoid in high maternal care pups (functioning stress response)
• Low levels of glucocorticoid in low maternal care pups (non-functioning stress response)
• Extra handling with brushes equalised differences between high and low maternal pups
• Those who were given care when they were young had low CRH as adults
• Those who were not (so the low, no extra handling group) had high levels of CRH as adults
Nothing to do with genes animals hold- all about functional expression of genes that they had that is important- environment alters this functional expression
Found that low maternal care resulted in tightly bound DNA to histones- high DNA methylation of genes in brain important for glucocorticoid receptors and other stress related gene systems
Found that high maternal care resulted in loosely bound DNA-histones had high levels of acetylation in stress genes
What is the agreed model for “inheritance” of maternal care?
Behaviourally inheritable trait- maternal care
• An animal behaves similarly to mother it is looked after by (cultural transmission)
• Not social learning that’s doing this
This behaviour is inducing an emotional change in the pups- different levels of childhood stress
Emotional change in pups substantiating itself into biology of brain through epigenetic changes to stress axis
Genetic change is maintained for natural life of individuals such that it changes their emotional responses in life- poor regulation of stress and anxiety for low maternal
This emotional expression influences the maternal care that they give later in life an adult
o It’s not the epigenetic regulation of “genes for maternal behaviour.”. It is an indirect effect via emotional regulation
Summary:
• The indirect effect on maternal behaviour:
o Not an environmental effect on genes for maternal behaviour
o Effect is on genes important for emotional regulation
o Poor emotional regulation then spreads to negatively affect other behaviours, including maternal care
Briefly describe the HPA axis (the neuroendocrine response to stressors)
• CRH is made in nerves in the hypothalamus and is released into the pituitary CRM/CRF= corticotropin releasing hormone/factor
• ACTH is released into bloodstream from the pituitary
o ACTH= adrenocorticotropic hormone
• Glucocorticoids are released from the adrenals
o Glucocorticoid= cortisol in humans, corticosteroid in lab rats
• Glucocorticoids have many effects on physiology and CNS to increase capacity to cope with stressors
• Loop is under control of glucocorticoid receptors in cortex, hippocampus and hypothalamus: these inhibit the release of CRH
Why is it hard to see clear links between genes and behaviours?
• This is one of the reasons why it’s so hard to see clear links between genes and behaviours
o Variations in a behavioural phenotype might be due to variations in genetic activity of genes important for other factors (e.g. underlying emotional, motivational, cognitive factors)
o Variations in these factors might be heavily influenced by environmental context
• This is why it’s important to understand the psychological factors that contribute to behavioural phenotypes
What structural features does a neuron have?
• Neuron has: o Cell body o Dendrites feeding into the cell body o One long axon covered in myelin or oligodendrocyte sheaths o Synapse-Space between the two neurons
What are the principles in the neuronal doctorate?
o Neurons are discrete cells
o Information/action potentials in a neuron travels in one direction (from cell body down to synapse)
o Synapse occurrence triggers postsynaptic neuron to form its own action potential
Describe the first part of the Loewi study
• First part
o Dissected out a rabbit heart and left intact the vagus nerve from the base of the brain onto the heart of the rabbit and put it into the solution
o If had correct nutrients in the bath that the heart was in the heart would continue to beat after taken out of rabbit
o If stimulated vagus nerve with electricity, could change rate of heartbeat
Electrical stimulation of vagus nerve which regulated cardiovascular activity in the rabbit
Describe the second part of the Loewi study?
• Second part
o Placed second dissected heart in a different vessel that was connected by a fluid bridge to the original vessel with the first heart
o Showed that if stimulated the vagus nerve and changed cardio activity of heart A, after a period of time, would also change activity of heart B
o Showed that stimulation of vagus nerve produced excretion of water soluble factor which then changed the activity of the cardiac muscle
o Not electrical stimulation directly causing the effect of the nervous stimulation of the cardiac muscle, but the release of some soluble chemical factor driving this effect
What happens at the synapse?
o Vesicles with neurotransmitters come down from the nucleus along microtubules to the presynaptic mass
They will then remain inactive
o An action potential will hit the synapse
o When this occurs, voltage change of the membrane caused by the action potential causes some transmembrane channels to open which are specific to calcium ions
o Calcium ions rush into the neuron which changes configurations of proteins surrounding the vesicles, making them stick to the intracellular presynaptic membrane
o Once stuck, proteins on extracellular presynaptic membrane causes vesicle to open
o Neurotransmitters in the vesicle are released into the synapse
o Once neurotransmitters released into the synapse, receptors on postsynaptic neuron mass are sticky to the neurotransmitters and bind to the neurotransmitters
o When receptors bind to neurotransmitters, they change the electrical gradient in post-synaptic membrane
More negative-makes it less likely for post-synaptic neuron to fire
Less negative- makes less negative, which makes it approach the firing threshold for the action potential
o Electrical chemical electrical system
o More points of control around ability for variable changes
What are the different classes/ subclasses of neurotransmitters?
Cholines
- Primary neurotransmitter from muscular nerves to muscles
- Also in CNS
Monoamines
- Catecholamines
- Indolamines
Amino acids
- Primary neurotransmitter in CNS/ the most abundant
- -Excitatory
- -Inhibitory
Peptides
-Opioids
Lipids
-Endocannabinoids
Nucleosides
-Purines
What is the endogenous ligand of cholines?
Acetylcholine Ach
What are the receptors for acetylcholine?
Nicotinic, muscarinic
What are the endogenous ligand of catecholamines?
- Dopamine DA (main neurotransmitter released in the reward circuit)
- Norepinephrine/Noradrenalin NA (same compound)
What is the endogenous ligand of indolamines?
Serotonin 5HT
What are the receptors for dopamine?
D1-5
What are the receptors for noradrenaline?
Alpha and beta adrenergic
What are the receptors for serotonin 5HT?
14 types of 5HT receptors
What are the amino acid excitatory ligands ?
Glutamate or Aspartate
-Glutamate is the most widespread excitatory neurotransmitter
What are the amino acid inhibitory endogenous ligands?
GABA
-GABA is the most widespread inhibitory neurotransmitter
What are the receptors for glutamate/aspartate?
NMDA (important for learning and memory) and kainite. AMPA and mGlu are the main ones in terms of nervous activity
What are the receptors for GABA?
GABA-A, GABA-B
What is the endogenous ligand of opioids?
Endorphins
What is the receptor for endorphins?
Opioid
What is the endogenous ligand for endocannabinoids?
Anandamide
What is the receptor for anandamide?
Cannabinoid
What is the endogenous ligand for purine?
Adenosine
What is the receptor for adenosine?
Adenosine, Purinergic
Where are neurotransmitters generated and what are the most commonly produced?
• Many neurotransmitters are generated in discrete nuclei that may project widely through the brain
o In every nucleus within the brain there are interneurons which generally release excitatory or inhibitory amino acids
Where are monoaminic neurotransmitters produced?
• For monoamines, only have a few places which release these types of neurotransmitters
o Only 2 nuclei make neurons that produce dopamine
Substantia nigra which projects into the striatal system
Ventral tegmental area projects into multiple parts of the brain important for emotional processing, and into the cortex
o Noradrenaline
Only one part of the brain generates neurons which produce noradrenaline
From this point, spread out around brain and release noradrenaline in various parts of the brain for various functions
o Serotonin
3 main nuclei which produce serotonin neurons but they spread all throughout nervous system to regulate activity of different nuclei in the brain
What is the purpose of receptors?
• Drugs bind to a receptor to generate a biological response
What is the binding mechanism between the ligand and the receptor?
o Binding is usually transient- the drug (ligand) sits in the binding domain for various periods of time (determined by strength of affinity-demonstrated by k coefficient) and dynamically binds through stochastic random process until the drug is metabolised
Will form a complex so that when receptor binds the drug some change in the shape of the receptor occurs such that intracellular tail of receptor produces some biological effect
What are the two major classes of receptor?
- Ionotropic
- Metabotropic
How do ionotropic receptors work?
Common type in the brain
Binding of neurotransmitter to receptor opens an ion channel which produces immediate change in the electrical potential of the neuron membrane
Immediate and rapid changes to neuronal activity
What are examples of ionotropic receptors?
• E.g. GABA- 4 subunits produce an ion channel which cross receptor membrane
o When receptor bound to channel, channel became open and opened to a degree which allows chlorine to come through from intracellular to extracellular space
o Makes interior of neuron more negative
More negative a neuron is, the harder it is for the neuron to generate an action potential which is why GABA is inhibitory
• Sodium ions can also come through some excitatory ion channel receptors to make the neuron more positive and hence encourage action potentials
Describe Type I metabotropic receptor mechanisms
Type I:
• Molecule of transmitter substance binds with receptor
• Receptor activates G protein
• Alpha subunit of G protein breaks away, binds with ion channel and opens it
• Ions enter cell, produces postsynaptic potential
Describe Type II metabotropic receptor mechanisms
Type II
• Molecule of transmitter substance binds with receptor
• Receptor activates G protein
• Alpha subunit of G protein breaks away, activates enzyme which produces second messenger
o The involvement of second messenger systems allows better integration of neural signals and more variation in how the cell might respond
• Ion channel opens
• Ions enter cell, produce postsynaptic potential
What is the speed of metabotropic receptors?
Because of the extra steps, these receptors have slower action
What are the effects of ligand-receptor complexes?
• The effects can be:
o Changing the post-synaptic membrane potential
Hyperpolarisation= less likely to fire
Depolarisation= more likely to fire
o Activating internal signals that can
Change gene expression and potentially the phenotype of the neuron
Increase the number of receptors on the surface making it more/less sensitive
Modify the activity of other metabotropic receptors
Why is neurotransmitter release and activity in the synapse tightly regulated?
• Neurotransmitters release and activity in the synapse is tightly regulated so that quicker pulses are transmitted from one neuron to another (signal sharp and quick so can have it more frequently)
What happens to a neurotransmitter after it has achieved its desired effect on the postsynaptic neuron?
• When they leave the postsynaptic receptor and go back into synapse after having done their job, they are taken back up by the presynaptic neuron by transporter proteins. They are then either:
o Re-packaged into vesicles for more use
o Destroyed by enzymes in the presynaptic neuron
What is an agonist?
drug which mimics a neurotransmitter spatial shape and results in corresponding change in resting potential
What is an antagonist?
drug which blocks a neurotransmitter at its receptor hence making sure that that receptor is not available for binding for natural neurotransmitter
• Antagonist still fits in receptor but shape is slightly different than required for signal production so just blocks the receptor
What are different ways (and some examples) by which agonist drugs can enhance neurotransmitter action?
o Enhancing release of neurotransmitter (L-Dopa enhances the production of dopamine)
o Binding directly to receptor
E.g. THC, Benzodiazepene, Heroin, Nicotine and Ethanol
o Blocking reuptake of neurotransmitter by blocking transporter proteins or reversing transporters so that they actually cause the release of neurotransmitters
E.g. MDMA, antidepressants, Cocaine, amphetamines
Some drugs reverse these transporters
o Blocking enzymes that destroy excess neurotransmitters
Catecholamines, MAOA (anti-depressant drugs which target serotonin and noradrenalin) and MAOB (which targets dopamine)
How do antagonist drugs prevent neurotransmitter and agonist drug action?
o Blocking receptors
E.g. Naloxone, ketamine, anti-psychotics
How do anti-depressant drugs enhance monoamine neurotransmitters? (Give examples)
o Selective serotonin reuptake inhibitors
Fluoxetine blocks reuptake of serotonin because they antagonise serotonin specific transporters in the presynaptic neuron
o Serotonin and norepinephrine reuptake inhibitors
Venlafaxine
o Tricyclic antidepressants
Work on reuptake/transporter
o Monoamine oxidase inhibitors stop degradation of neurotransmitters so increase supply of neurotransmitters
How were the earliest anti-depressants developed?
• Earliest anti-depressants were discovered by accident
o Iproniazid was originally used for tuberculosis but researchers noticed that patients experienced a relief of their depression
o Was then discovered to inhibit Monoamine oxidase (an enzyme that breaks down monoamines such as noradrenaline, dopamine and serotonin) and elevate serotonin
o Reserpine was an anti-hypertensive that depleted monoamines and caused depression
What are the drawbacks of newer MOA’s?
• Newer MOAs were developed but they are still associated with severe side effects
o Were effective for some types of depression but had severe side effects, one of these being tyramine-derived symptoms
• Side product of tyramine is severe in people and MOA inhibitors break down tyramine naturally
• Compounds can accumulate in body and become toxic
What is the focus of the latest anti-depressant drugs and what hypothesis did it lead to? But what is the problem with this hypothesis?
All later effective drugs were designed to increase synaptic monoamines
o Tricyclic antidepressants block reuptake pump, which consequently leaves more neurotransmitter in the synapse
o Selective serotonergic reuptake inhibitors have been developed to block reuptake of serotonin alone.
o This lead to the idea that depression may be related to insufficient cortical or limbic monoamines, NA, DA, 5HT
o But:
There’s a therapeutic lag in the action of anti-depressant drugs (need to be given for 3 weeks)
• Monoamines increase immediately after starting the therapy, but the therapeutic effects can take weeks
Acute effect of anti-depressant drugs can be worse depression when first start taking the drug
• Perhaps it’s not the acute effect of elevating monoamines, but a chronic downstream effect caused by this
Describe the receptor sensitivity hypothesis and how it works with serotonin receptors
• Could be change to sensitivity to monoamines in the brain
• In particular, for serotonin receptors, too many 5HT1A on pre-synaptic neurons and 5HT2A receptors on post-synaptic neurons which have regulatory effects in the pre-synaptic neuron
• Chronic elevation of 5HT causes these receptors to be reduced over time and their sensitivity reduced
• In metabotropic receptors, heightened stimulation of 5HT2A receptors (and other receptors too) causes the neurons to initiate other cellular changes e.g. gene expression
o Upregulation of other receptors
o They start making hormones (called trophins) that initiate formation of new synapses, or that cause the growth of new neurons
• Link to depression may not be amount of serotonin made, but number of receptors on the neurons
• This normalises synaptic function
What is the exogenous agonist/antagonist equivalent to acetylcholine?
Nicotine
What is the exogenous agonist/antagonist equivalent to dopamine?
Cocaine, amphetamine
What is the exogenous agonist/antagonist equivalent to noradrenalin?
Beta-blockers
What is the exogenous agonist/antagonist equivalent to serotonin?
MDMA/ecstasy, LSD
What is the exogenous agonist/antagonist equivalent to glutamate?
Ketamine, PCP
What is the exogenous agonist/antagonist equivalent to GABA?
Benzodiazepenes, alcohol
What is the exogenous agonist/antagonist equivalent to endorphins?
Heroin, morphine
What is the exogenous agonist/antagonist equivalent to anandamine?
THC in cannabis
What is the exogenous agonist/antagonist equivalent to adenosine?
Caffeine
How is L-Dopa produced/used?
• L-Dopa and subsequent production
o Tyrosine is turned into L-Dopa through tyrosine hydroxylase action
o L-Dopa is turned into Dopamine through DOPA carboxylase action
o Dopamine is turned into noradrenaline through Dopamine beta-hydroxylase action
