Genetics, Development, and Neuroplasticity Flashcards
Define what a gene is. Define what an allele is.
gene = a section of DNA containing information used to build a protein (ex: eye color, blood type, skin color)
allele: variant of a specific gene (blue eyes, green eyes, type A blood, black skin, white skin)
Understand that DNA holds instructions for making proteins
DNA sequence of a gene determines the amino acid sequence for the protein it encodes
DNA builds proteins —> DNA contains genes —> gene sequences form amino acids —> amino acids link together to form long chains —> chains of amino acids = proteins
—> traits determined the function of proteins, which is determined by structure, which is determined by amino acid sequence
(which is determined by genes found in DNA)
DNA—>builds protein
Describe different types of allelic variants (insertions, deletions) and broadly what
effects they might have
Can be insertions:
add one extra base
GGCTATTCC —> GG[CCG]GTATTCC
Can be deletions:
remove one base
GGCTATTCC —> GGCTCC
Can lead to changes in the proteins that are created
or changes in the switches that control when/where a protein is active and how much protein is made
—> frameshift mutation: can change ever amino acid that follows the point of mutation — altering a protein so much that it can’t perform normal functions
Explain how optogenetics works, based on your understanding of genetics
Optogenetics uses light-gated channels
light-sensitive protein from algae —> insert the DNA into specific neurons in the brain —> neuron firing functions on the opening and closing of ion channels —> now they can fire just on light
Explain why it’s probably not useful to say, there’s a gene for ______ [some behavior] or
[some psychiatric disorder] or [some trait].
most human traits are influenced by so many genes that there is no likely systematic cause and effect
nature vs. nurture:You inherit genes from your biological parents that determine your eye color, but do you inherit genes that determine your behavior and personality?
Describe what Williams Syndrome is – what causes it, what the symptoms are, findings related to hypersociality and amygdala activity, why it’s a particularly interesting case to understand connections between genes/brain/behavior
deletion of chromosome 7
(removing 20+ genes that encode for different functions)
PHSYICAL EFFECTS: specific facial characteristics, dental abnormalities, heart problems, differences in growth patterns
COGNITIVE EFFECTS: poor memory, learning difficulties, low IQ, poor visuospatial skills
BEHAVIORAL EFFECTS: hyper-sociality, affinity for music
—-
people with WS show less activity in the amygdala in response to fearful faces
—> greater likelihood of approaching strangers in
WS associated with less amygdala activity
Explain the findings regarding short vs. long alleles for the gene that codes for the serotonin transporter and depression
Different alleles for the gene that codes for serotonin transporter
“Short” alleles produces less mRNA, creating fewer serotonin transporters
“Long” allele produce more mRNA, leading
to more serotonin transporters
People with at least one copy of the short allele
exhibited more depressive symptoms in relation to
stressful life events than those with the l/l alleles
Explain what is meant by gene expression
If all cells contain the same DNA, how is it that we
have such a great diversity of cell types?
Gene expression: A gene is “turned on” and
produces a protein
Differential gene expression makes cell types
different – in development and in adulthood
—> in every cell, biological machinery constantly translates DNA into the proteins needed to carry out vital processes
—> chemical switches attached to the DNA turn genes on or off, telling the DNA to produce certain proteins at certain quantities
—> these proteins are called epigenetic tags, cells contain the same DNA but express different traits
Define what genotype and phenotype are
Genotype: genetic makeup of an organism
• Phenotype: traits of an organism
• Phenotypic variation: organisms differ in their traits
and behavior
Explain the two sources of information that DNA contains
DNA holds two sources of information: sequence and structure
The DNA sequence (or genome, e.g.,
CATTGGATTCCGGA…) —> generates proteins
The DNA structure (or epigenome) —> serves as an
“on/off” switch for gene expression
Provide evidence discussed in class of gene x environment interactions
gene-environment interaction occurs when the effect of an environmental exposure on health and behavior is conditional upon a person’s genotype
Phenotype is the product of gene x environment
interactions: Gene x Environment —> Phenotype
interaction of gene in environment
ex: DRD2 can’t break down alcohol —> genetic predisposition of addiction
Explain the meaning behind the analogy that our DNA is like books in a library
like a library, DNA has different sections (chromosomes), each section has lots of books (genes), each book contains instructions for something
Define and explain what epigenetics and epigenetic mechanisms
DNA methylation: methyl groups “silence” genes
Histone modification: makes DNA less readable by
not allowing it to unwind
Demonstrate a thorough understanding of the series of studies associated with the Agouti mouse, i.e., what happens in the primary study where we look at how changes in methylation affect expression of the mutation on the agouti gene, but also understand
what happens when pregnant mice with these mutations are exposed to BPA and to nutrient-rich diets.
—> mutation of Agouti gene (insertion)
—> mutation leads to a variety of phenotypic changes (yellow coats and prone to obesity, diabetes, and cancer)
But methylation can “silence” the expression of this mutation
—> the mice have the agouti gene mutation, but it’s not expressed; they’re as healthy as mice without the mutation
Greater number of yellow, unhealthy pups were born to pregnant mothers exposed to BPA
—> maternal exposure to BPA decreased DNA
methylation in offspring
Pregnant mothers exposed to BPA
• Greater number of yellow, unhealthy pups were born
• Maternal exposure to BPA decreased DNA
methylation in offspring
But BPA + a nutrient-rich diet (folic acid, soy products): —>had more brown, healthy pups —>maternal nutrient supplementation can counteract negative effects of BPA exposure
Provide examples of some sources of epigenetic variation
factors affecting epigenetic variation: stress, drug use, social interactions, pesticides, smoking, hormones, nutrition
Understand that rearing behavior can affect pups epigenome and lead to differences in anxiety levels
Nurture shapes rat pup’s epigenome
- Pup raised by anxious, low-nurturing mom —>anxious adult
- Pup raised by relaxed, high-nurturing mom —>relaxed adult
Discuss why it is somewhat silly to talk about nurture vs. nature, and especially so given what we know now about epigenetics
in addition to nature and nurture, what makes us who we are is also determined by biological mechanisms that can switch genes on or off
both genetic and subject to environmental influences —> so both!
Explain why it’s valuable to study the astronaut twins.
helps us to better understand how nature and nurture work together
Provide examples of experience-independent, experience-expectant, and experience-dependent
aspects of development and explain why you’d categorize these examples the way you did.
EXPERIENCE-INDEPENDENT: parts of brain = preprogrammed
—-> ex: babies born with reflexes, baby calfs can walk after exiting womb
—-> chemoaffinity hypothesis: axons have pre-specified targets independent from experience (Sperry’s newt experiment)
EXPERIENCE-EXPECTANT: during sensitive period, the brain “expects” to be exposed to experiences such as visual content, sound (voices), and bodily movement; evolution has conditioned brain to expect these stimulating experiences —> needed to activate synapses involved in sensory perception and health brain development
—-> synaptogenesis (formation of synapses) (visual cortex—>prefrontal cortex development) (sensory pathways—>language—>higher cognitive functions)
—-> ex: newborns need to have visual input to develop healthy sight perception
EXPERIENCE-DEPENDENT: Neural connections that form in response to a person’s life experiences — different life situations and circumstance influence how certain areas of the brain develop and continue to grow.
—-> ex: eskimo child knowing how to build igloo
—-> ex: enriched vs. deprived rat environments: animals raised in a complex and engaging environment have more dendrite development and more overall synapses than do animals who are raised in an environment with no stimulation
—-> ex: Held & Hein cats: raised cats in total darkness —> 1hr/day, kittens exposed to light —> one cat was able to walk, the other placed in box and moved around cylinder —> only the kitten who controlled its own motor movements (thus learning the proper relationship between action and visual feedback from the world) developed normal vision —> SHOWED NEURONAL NETWORKS ARE DEPENDENT ON EXPERIENCE (REQUIRE INTERACTION WITH WORLD) IN ORDER TO PROPERLY DEVELOP
Describe in very broad strokes the course of human brain development in utero; I’m posting the HHMI video
Prenatal period:
• 3 weeks gestation: brain and nervous system begin
to develop
• 4 weeks gestation: see major regions of the brain
• 6 months gestation: see gyri & sulci
results, and significance of Sperry’s experiments on newts
goal: how much of the brain is hardwired?
why each nerve fibre has a pre-assigned address?
—> so he cut the optic nerve of an adult newt and rotated its eyeball upside down (nerve fibers regenerate in amphibians)
—> WOULD FIBRES FROM THE EYE GROW BACK INTO THEIR ORIGINAL ORIENTATION IN THE OPTIC TECTUM OR WOULD THEY TWIST AROUND TO MATCH THE WORLD
when the fibres regrew, they plugged into their original pattern
—> led Sperry to conclude that the fibres do not find their destinations by visual experience, but instead by preprogrammed signaling
IN SPERRY’S CHEMOAFFINITY HYPOTHESIS: EACH INCOMING AXON MAKES A CONNECTION WITH THEIR TARGET BASED ON SPECIFIC CHEMICAL SIGNALS RELEASED BY THE TARGET
Explain how plasticity changes over the course of the lifetime
Explain why a two-year-old has more synapses than an adult
tradeoff between plasticity/flexibility and efficiency
Brain is most plastic (flexible) early in life; over
time, it gets more specialized for complex functions
and reorganization/adaptation is harder.
—>young brains: generalized activity without attentional focus; many cholinergic transmitters but not inhibitory ones —> allow for global change —> babies = R&D department
—>adult brains: attention causes widespread cholinergic release, which allows for changes in tissue—this is counterbalanced with inhibition in areas that should not change
Explain graphs depicting different rates of synaptogenesis and pruning for brain areas
involved in different functions
cortical development
pathway development
gray vs. white matter
synaptogenesis (formation of synapses)
- visual cortex—>prefrontal cortex development (prefrontal and lateral temporal cortices are the last to mature) —> [front to back pattern]
- sensory pathways—>language—>higher cognitive functions
- Gray matter volume peaks in teenage years
- White matter volume increases into adulthood
-newborn-2 yrs: synapses formation
4-6 years: synapse pruning
WHY? —> need basic survival skills before critical thinking skills : reduction of synapses leaving more efficient synaptic configurations —> pruning influenced by experience “you use it or you lose it”
Explain how autism spectrum disorder might be conceptualized in part as associated
with differences in synaptic connections
Autism is associated with alterations in synaptic connections
—-> too many, too few, too strong, too weak synapses or in wrong place
—> excitatory and inhibitory synapses = abnormal balance (too many synapses=excitatory=overstimulation, too few=inhibitory=understimulation)
balance between inhibitory and excitatory synapses is thought to be important for establishing critical periods
infants with ASD experienced “hyperexpansion” of brain’s surface in first year of life and subsequent rise in brain volume
Explain why it might be an advantage that our brains take a long time to develop
our delayed cortical development is precisely what enables us to acquire the cultural building blocks, such as language, that make up the foundations of human achievement
tradeoff between plasticity/flexibility and efficiency
Explain what the chemoaffinity hypothesis is
Axons find their way to targets based on molecular cues
Describe some reflexes babies are born with
breathing, eye blinking, swallowing, grasping, Moro reflex (arms out)
rooting (touch cheek, turn head and open mouth for nursing—”rooting reflex,” an instinctive search for food)
Explain the methods, results, and significance of the experiment with the kittens in which one kitten could move of its volition and the other just rode a sled yoked to the first kitten’s movement
ex: Held & Hein cats: raised cats in total darkness —> 1hr/day, kittens exposed to light —> one cat was able to walk, the other placed in box and moved around cylinder —> only the kitten who controlled its own motor movements (thus learning the proper relationship between action and visual feedback from the world) developed normal vision —>
SHOWED NEURONAL NETWORKS ARE DEPENDENT ON EXPERIENCE (REQUIRE INTERACTION WITH WORLD) IN ORDER TO PROPERLY DEVELOP
Explain how we treat children with strabismus and why the timing is important
strabismus: misaligned eye —> visual system did not wire up properly —> favor one eye/bad vision other eye (amblyoplia) —> dominant eye takes over weaker eye’s territory
constraint therapy
—>correction of strabismus must occur during critical period for visual system development
Briefly describe the findings of the study looking at how the sounds of moms’ voices affect brain development in babies born prematurely
Sound of mom’s voice boosts brain growth in premature babies
Infants born prematurely are more than twice as likely to have difficulty hearing and processing words than those carried to full-term, likely because brain regions that process sounds aren’t sufficiently developed at the time of delivery —> babies exposed to mother’s voice SIGNIFICANTLY THICKER AUDITORY CORTICES THAN CONTROL GROUP
Describe what neurotrophins do
neurotrophins promote neural growth and survival
- proteins secreted by neuron targets that enable the development, survival, and function of neurons
- enable neurons to make and keep connections
- prevent neurons from initiating apoptosis
currency over which the neurons and synapses compete for real estate —> drive neurons to makes connections then stabilize those connections
—> promote growth, survival, guide axons, and stimulate development of new synapses
Describe what happens in the brain when rats are kept in standard cages vs. “enriched” cages
ex: enriched vs. deprived rat environments: animals raised in a complex and engaging environment have more dendrite development and more overall synapses than do animals who are raised in an environment with no stimulation
Describe what myelination is and the overall time course of myelination, particularly how certain areas (you should know which ones) are not fully myelinated until late adolescence/early adulthood at least
myelination= formation of myelin sheath around nerve fibers
-Begins ~29 weeks gestation
-many major tracts not fully myelinated until
adolescence and beyond…
some areas of the brain mature faster than others
—> areas associated with reward, motivation, and impulsivity mature early
—> prefrontal cortex matures later in life (logic, reason)
—> teens therefore can be MORE PRONE TO RISKY/IMPULSIVE BEHAVIOR — less likely to think about consequences
—> risk vs. reward: more likely to think the latter outweighs the former
Cajal said, “Everything may die, nothing may be regenerated.” Was he correct?
old dogma —> neurogenesis/plasticity
Dynamic changes in brain structure/function in response to interaction with the external environment or internal goals
Define neuroplasticity
ability for brain to change its neural pathways and develop new functions (in response to learning/experience/damage/etc.)
Describe what happens in a hemispherectomy, why a family might elect it, and how the brains of children respond after such surgeries
Rasmussen’s encephalitis = inflammatory disease that affects 1/2 of brain —> causing severe epileptic seizures
treatment: hemispherectomy
remove 1/2 of brain/cerebrum —> empty half fills up with cerebrospinal fluid
—> REMAINDER OF BRAIN REWIRES TO TAKE OVER MISSING FUNCTIONS
Describe the results of the fMRI study that looked at early blind and control participants while they did auditory and tactile processing tasks. What do these results tell us about plasticity?
Blind more sensitive to touch and hearing
—> cortical space that would have gone to visual input is taken over by other sensory mechanisms
—> fMRI: auditory and tactile tasks activate visual cortex of early blind patients
Brain makes use of available cortical area
Although we didn’t spend a great deal of time talking about it in class, be able to describe some of the key points/themes raised in the Somerville (2016) article
not scientifically accurate
cross-sensory phenomenon is known as synesthesia (heard vs. saw)
subjects’ brains responded to the sound of their phones as they would respond to the presence or proximity of a girlfriend, boyfriend or family member
causation vs. correlation
How are the brains of musicians generally different?
What can we conclude from studies that just compare the brains of people with a skill (e.g., musicians) vs. those without?
brain reflects animal’s actions/goals
differences in behavior reflected anatomically
Omega sign gyrus (present in musicians only, keyboard players had it on left, string players showed it on right)
responsible for motor hand area
Describe the methods and results of the series of juggling studies. What conclusions can we draw from these studies?
juggling training for 3 months:
• MRI before training, during training, and after training
changes in grey matter and white matter —> both increase
significant expansion was found in two areas (the mid-temporal area and left posterior intraparietal sulcus) within the brains of jugglers (important in processing information related to moving objects)
—> learning new skills can alter brain structure
Be able to locate the basal forebrain and describe why it’s an important area, particularly vis-à-vis plasticity.
basal forebrain = contains nucleus basilus, which distributes the cholinergic neurotransmitter [acetylcholine] broadly throughout the cortex
Describe the methods, results, and significance of the study involving two groups of rats, one group with lesions to the basal forebrain
although it is said that practice makes perfect…practicing a task is not enough to change the brain in absence of the plasticity-enhancing powers of cholinergic neurons
lesioning the nucleus basilus in the basil forebrain of group of rats —> task: grab sugar pellets through slot —> two weeks of practice in control group led to 30% increase in the size of the cortical area devoted to forepaw movement and MOTOR SKILLS AND SPEED IMPROVED —> cortical area shrank in affected group by 22% and accuracy for reaching for sugar pellets never improved
THE BASIS FOR PLASTICITY AND IMPROVED PERFORMANCE IS NOT SIMPLY REPEATING A TASK, BUT ALSO REQUIRES NEUROMODULATORY SYSTEMS TO ENCODE THE RELEVANCE OF THE TASK
~~ Adaptive coding
Explain a theoretical model for how rapid changes in plasticity occur
rapid changes to the brain’s circuitry suggests that there does not need to be large-scale rewiring, but instead there are inhibited connections that need to be unmasked
there are many neural connections that already exist —> but bc they are inhibited, they have no effect —> when dominant pathways lose active input, previously-masked ones take over
Explain to explain a theoretical model for how slower changes in plasticity occur
longer-term changes are thought to involve the growth of axons in new areas and the sprouting of new connections
growth of new axons and synapses
Describe the role of neuromodulation in plasticity
What are neuromodulators? What distinguishes a neuromodulator from a neurotransmitter? Can a chemical serve as both a neuromodulator and a
neurotransmitter?
the brain can essentially turn plasticity on and off in particular places at particular times, according to the animal’s needs (relevance)
this is called gating —> (the ability to allow changes to occur only when something important happens)
attention causes widespread cholinergic release, which allows for changes in tissue—this is counterbalanced with inhibition in areas that should not change
cholinergic release tends to be broadly distributed, not precise, and is counterbalanced by inhibitory neurotoassnmitiers of self-modulation
neuromodulators are neurotransmitters that are not reabsorbed by the pre-synaptic neuron or broken down
ex: acetylcholine ~~ neurons that release acytylcholine are called cholinergic (basal forebrain)
phonemes
perceptually distinct units of sound
frog experiment and implications for neuroplasticity
EXPERIMENT 1:
cortical map adjusts itself to available brain tissue
—>nerves from the eye travel to optic tectum
(each nerve fibre has preassigned address in the optic tectum)
—> to understand the principles of plasticity, researchers removed half of the optic tectum during development, before the optic nerves had arrived
—> a full retinotopic map developed on a smaller piece of real estate
SPERRY’S EXPERIMENT 2:
—-> Sperry inserted a third eye into tadpole —> inputs shared the same tectum
SHOWED THAT CORTICAL MAPS CAN COMPRESS OR EXPAND DEPENDING ON AMOUNT OF REAL ESTATE — MAXIMIZING SPACE
NEUROPLASTICITY: BRAIN ADAPTS TO ENVIRONMENT TO MAXIMIZE COMPETITION AND EFFICIENCY
Outline the steps of brain development
brain development: PMDSAP (practice moving different series around me)
- proliferation (cells are reproducing themselves)
- migration (cells are traveling to their destination)
- differentiation (cells specializing for different functions)
- synaptogenesis (creation of new synapses between cells)
- apoptosis and pruning (selective cell death and paring back of synapses)
- myleination (insulting axons to improve speed/efficiency/stability)
sensitive period vs. critical period
Critical period: time in which stimuli MUST occur in order for normal development
ex: developing proper sight
* **correction of strabismus must occur during critical period for visual system development
Sensitive period: time when particular development occurs most easily
ex: learning second language
pathways are developing and refining most rapidly, when brain is most plastic
Autism (ASD)
Synaptic connections between neurons are believed to be altered in autism. There can be too many or too few synapses (see left and center), or synapses may be too strong or too weak or even occur at the wrong place. What’s more, the balance between excitatory and inhibitory synapses may be abnormal (see right). That balance is thought to be important for establishing critical periods—the developmental windows where our environment has the most influence on our brain circuits.
Gray matter vs. white matter in brain development
Gray matter = cell bodies
White matter = axons/myelin
gray matter is where all the thinking happens, the “processing center”
—> gray matter develops quickly in childhood, slows in adolescence —> then declines (makes the adolescent brain very versatile) U-SHAPE GROWTH
white matter is the “super highway” transferring information to different parts of brain
—> develops continuously from birth onwards, slight increase in puberty LINEAR GROWTH
Implications of brain development on the adolescent brain
some areas of the brain mature faster than others
—> areas associated with reward, motivation, and impulsivity mature early
—> prefrontal cortex matures later in life (logic, reason)
—> teens therefore can be MORE PRONE TO RISKY/IMPULSIVE BEHAVIOR — less likely to think about consequences
—> risk vs. reward: more likely to think the latter outweighs the former
Relationship between rapid and slow models of neuron connections
if short-term/rapid connections (unmasking) are found useful to animal, then long-term/slow connections (growth of new axons) will follow
