Development of the Central Nervous System Flashcards
(97 cards)
1
Q
What are the stages of development of the central nervous system?
A
- Prenatal
- Post natal
- Childhood
- Adolescence
- Adulthood
2
Q
What are 2 disorders of neurodevelopment?
A
- Autism Spectrum Disorder
- Williams Syndrome
3
Q
What is brain plasticity?
A
- CNS continues to change throughout our entire life (level of plasticity changes)
4
Q
What must neuronal cells do after formation?
A
- Differentiate (muscle cells, liver cells, neurons, glia)
- Migrate to the appropriate function
- Establish functional relations with other cells
5
Q
What are the 4 key steps of cellular differentiation?
A
- Totipotent
- Pluripotent
- Multipotent
- Unipotent
6
Q
What is the totipotent stage?
A
- Early embryonic cells
- Can differentiate into any cell type of the body
7
Q
What is the pluripotent stage?
A
- Initial differentiation
- Cells can still become many, but not all, cell types
8
Q
What is the multipotent stage?
A
- Cells that can develop into multiple cell types within a class of cells (e.g. neural cells)
9
Q
What is the unipotent stage?
A
- Cells that can only complete their differentiation into one cell type
- Completed differentiation
10
Q
What are the 2 properties of stem cells?
A
1 - Unlimited divisions without differentiation
2 - Potential to differentiate into different cell types
11
Q
What are 3 different types of stem cells?
A
- Totipotent stem cells
- Pluripotent stem cells
- Multipotent neural/glial stem cells
12
Q
What are the 5 stages of embryonic development of the CNS?
A
1 - Induction of the neural plate 2 - Neural proliferation 3 - Migration and Aggregation 4 - Axon growth and synapse formation 5 - Neuron death and synapse rearrangement
13
Q
What are the 3 embryonic germ layers?
A
- Ectoderm
- Mesoderm
- Endoderm
14
Q
What 3 structures form from the ectoderm?
A
1 - Neural plate (thickening in dorsal portion; 18 days)
2 - Neural groove (invagination; 21 days)
3 - Neural tube, Central canal and neural crest (encloses completely; 24 days)
15
Q
What is induction?
A
- Mesoderm triggers formation of neural plate
16
Q
List the early developmental structures of the mammalian brain from anterior to posterior?
A
- Telencephalon (cerebral hemispheres)
- Diencephalon
- Mesencephalon (midbrain)
- Metencephalon
- Myencephalon (medulla)
- Spinal cord
17
Q
What is neural proliferation and when does it happen?
A
- After closure of neural tube
- Mostly in ventricular zone
- Species-specific sequences
- Regulated by chemical signals from floor plate and roof plate
18
Q
What are 3 directions that neural cells can migrate?
A
- Radially
- Tangentially
- Multipolar
19
Q
What are 2 forms of neural migration?
A
1 - Glial mediated locomotion
2 - Somal translocation
(Guided by chemicals that either attract/repel migrating cells)
20
Q
What is glial mediated migration?
A
- Radial only
- Travel along radial glial cells from ventricles -> surface
21
Q
What is migration by somal translocation?
A
- Radial or tangential
- Neuron grows processes, then reabsorbs process to soma moves to that position
22
Q
What are cell-adhesion molecules?
A
- On the surface of cells
- Used for migration, recognition, and adhesion
23
Q
What are gap junctions?
A
- Connexins-connexon
- Neurons form single connecting channel
- Directly communicate and coordinate function
24
Q
What are 3 neuron migration disorders?
A
- Kallmann syndrome
- Dyslexia and schizophrenia
- Lissencephaly
25
What is Kallmann syndrome?
- Abnormal genitals and dysfunctional sense of smell related to failed migration of neurons secreting sex hormones and coding for odors
- Genetic mutation related to CAMs
26
What is lissencephaly?
- 'smooth' brain
- Severe mental retardation
- Sensory/motor impairment
- Short life
- No cerebral cortex
27
What is the growth cone?
- At the tip of a growing axon, it extends and retracts filopodia
- Senses chemicals in the environment
28
What are the 2 hypotheses that describe how the growth cones find their way to the desired target?
1 - Chemoaffinity hypothesis
| 2 - Topographic gradient hypothesis
29
What is the chemoaffinity hypothesis?
- Target-specific chemical labels
- Axons grow into the chemical gradient (target releases chemical)
Hypothesis supported by:
- In vitro studies (no spatial cues, only chemical)
- Discovery of several such chemical labels
30
What is Sperry's classic study of eye rotation and regeneration?
- Rotate eye, then misshoot by whatever degree rotation occurs
- BUT retinal ganglion cells regeneration does not occur in mammals
31
What evidence does not support the chemoaffinity hypothesis?
1 - Targets transplanted in new positions can become incorrectly innervated
2 - It is often the case that the route to the target is circuitous, rather than linear
32
What does the revision of the chemoaffinity hypothesis state?
1 - Pioneer growth cones follow CAMs and other guidance molecules (chemical trials)
2 - Subsequent growth cones follow the pioneer growth cones via fasciculation (tendency of growing axons to follow previous axons)
33
Describe the topographic gradient hypothesis?
- 2 intersecting gradients (up-down and left-right) of chemicals on originating tissues guide axonal growth from one topographic array to another
- Supported by maintenance of topographic integrity (reciprocal position)
34
What is synaptogenesis?
- Synapse formation
| - Neuron-neuron chemical 'talk'
35
What is the role of glial cells in synaptogenesis?
1 - In vitro studies: neurons cultured with astrocytes form 7x as many synapses as those without astrocytes
2 - In vivo studies: synapse-promoting and inhibiting signals interact
36
What are 2 functions of neuronal death?
1 - Neurons that make incorrect connections die
- > Developing neurons are very promiscuous
- > Make lots of connections; not all are essential
2 - New neurons make more focused synapses
-> Cell death increases overall accuracy of synaptic connections
37
What is apoptosis?
- Active process of cell death
- A 'clean' process
- Cellular parts wrapped in a vesicle and removed by scavenger cells
38
What is necrosis?
- Passive cell death
- A 'dirty' process
- Die for other reasons (damage, stroke, etc)
39
What are 2 things that cause neurons to die?
1 - Genetically programmed
| 2 - Competition for target-supplied neurotrophins
40
What is nerve growth factor?
- First neurotrophin to be isolated
- From targets of sympathetic neurons (PNS)
- Therapeutic potential in nerve damage and neurodegenerative diseases
41
What are the 5 functions of neurotrophins?
1 - They promote neuronal growth
2 - They promote neuronal survival
3 - The can function as axon guidance molecules
4 - They can stimulate synaptogenesis
5 - Their absence can actively trigger apoptosis
42
When does the CNS fully mature and what is the last region to develop?
- Late adolescence
| - Prefrontal cortex
43
What does postnatal development of the CNS consist of?
- Synaptogenesis
- Myelination
- Dendritic branching
- Axonal growth
- Neurogenesis
44
What is synaptogenesis and when does it occur?
- Peaks after birth in most brain areas
- Primary visual/auditory cortex = 4-8 months
- PFC = second year
45
What is myelination and when does it occur?
- Roughly parallels functional development
- Sensory areas = first few months
- Motor areas = Soon after sensory areas
- PFC = continues into adolescence
46
What is dendritic branching and when does it happen?
- Parallels pattern of migration
- Deeper layers migrate first and are first to sprout dendrites
- Increasing connectivity
47
What is regressive changes/pruning?
- Periods of synaptic loss/refinement
48
What does postnatal development of the prefrontal cortex include (4)?
1 - Working memory (temporary memory used while a task is being performed)
2 - Planning and carrying out sequences of action
3 - Context dependent inhibition of inappropriate responses
4 - Following rules for social behaviours
49
What did Diamond's study show?
- Infant monkeys made lots of preservation errors
| - Adult monkeys with lesions in prefrontal cortex made the same amount of preservation errors
50
What is the Wisconsin card sorting test and what is it used for?
- Test preservation/frontal lobe function in adults
1 - Draw one card at a time and sort them
2 - Experimenter says whether well sorted
3 - Patient guesses sorting rule
4 - Experimenter changes rule
5 - Patient cannot adjust = preservation error
51
What are 2 types of experiences?
- Permissive experiences (ex. visual development)
| - Instructive experiences (not necessary; can drive/help development)
52
What are 3 studies on early sensory deprivation/enrichment?
1 - Animals reared in the dark = vision problems and fewer synapses in visual cortex
2 - Rats reared in enriched environment = various effects on brain structure/function (thicker cortices, more synapses, more dendritic spines)
3 - Babies with congenital bilateral cataracts = rapidly improve vision post-removal but retain some deficits
53
What happens when retinal ganglion axons are sent to the medial (rather than lateral) geniculate nucleus?
- Auditory cortex becomes organized like visual cortex
54
What are 4 possible mechanisms for how experience effects neurodevelopment?
1 - Direct gene regulation
2 - Neurotrophin release regulation
3 - Regulation of spontaneously active neural circuits
4 - Effects of specific neurotransmitters on development
55
What is adolescence?
- Transition period b/n childhood and adulthood
56
What does adolescent behaviour involve?
- Moody, impulsive, maddening, dopey, clumsy
- Angst, idiocy, haste, impulsiveness, selfishness, reckless bumbling
- High novelty seeking
- High risk taking
- Highly sensitive to peer influence
- Progressively better at balancing impulse, desire, goals, self-interest, rules, ethics, empathy, altruism
57
What happens in the brain during adolescence?
- Massive reorganization
- Axonal branching/pruning
- Progressively increasing axonal myelination (= faster axonal transmission)
- Strengthening of used and loss of unused synapses
- Overall thinning of cortex, but more efficient
- Progressive thickening of corpus callosum
- Enhanced frontal-temporal lobe connections
- Direction of changes is posterior to anterior
58
How did G. Stanley Hall describe adolescence?
- Replicates earlier, less civilized stages of human development
59
How did Sigmund Freud describe adolescence?
- Psychosexual conflict
60
How did Erik Erikson describe adolescence?
- Most tumultuous of life's several identity crises
61
What are the 2 current views on adolescence?
- Adolescents act oddly because brains aren't done; a work in progress; neuronal gawkiness = physical awkwardness
- Adaptive changes, new learning, useful experiences, develop social skills; 'helps get out of the house and into new turf'
62
Why is novelty seeking important in adolescence?
- New experiences
| - New learning
63
Why do adolescents take risks?
- Not due to undervaluation of risk
1 - Normal recognition of their own mortality
2 - Over-estimation of risk
3 - Different risk vs reward weight
64
Why is peer influence during adolescence important?
```
- Development of social behaviour
1 - Develop social skills and bonds
2 - Seek peer approval
3 - Enhanced peer competition
4 - 'wean' from parents, project towards others
```
65
In the adolescent brain, which neurotransmitters are most effective?
- Enhanced sensitivity to dopamine
| - Enhances sensitivity to oxytocin
66
What is the plasticity of the brain like during adolescence?
- High dendritic/synaptic remodeling (greater plasticity/flexibility when needed most)
- High myelination reduces axonal branching and making of new synapses (reduced plasticity)
- Set crucial brain connectivity for later in life
67
What is the plasticity of adult brains like? What 2 processes contribute to this?
- Retains high degree of plasticity
- Most new cells enter apoptosis
1 - Neurogenesis
2 - Experience-induced cortical reorganization
68
What did Fernando Nottebohm find?
- Neuroplasticity and neurogenesis in adult animals (song birds)
69
Which 2 areas of the brain are most plastic in adulthood?
- Olfactory bulb
| - Hippocampus/dentate gyrus
70
How does neurogenesis in olfactory bulbs occur?
- Occurs in subventricular zone
- New stem cells
- Glia-mediated migration
- Interneurons
71
What does hippocampal neurogenesis consist of?
- Occurs in subgranular zone
- New stem cells
- Dentate gyrus granule cells (e.g. environmental enrichment)
- Affects learning/memory
72
What are 5 functions of neurogenesis in adults?
```
1 - Form new memories
2 - Update old memories with new information
3 - Pattern separation
4 - Regulation of mood/anxiety
5 - Adapt to complex environments
```
73
What are some examples of experience-induced cortical reorganization in adults?
- Reorganization of sensory and motor maps
| - Ex. learning an instrument, London taxi drivers
74
How often does autism occur?
- 1 in 68 births (debate on incidence)
75
What are 2 symptoms of diagnosis for ASD?
1 - Reduced capacity for social interaction and communication
2 - Restricted/repetitive patterns of behaviour, interests or activities
76
What are 3 other frequent non-diagnostic co-symptoms of ASD?
1 - 75% are males
2 - Many suffer from intellectual or learning disability
3 - Many suffer from epilepsy
77
How has the prevalence of autism changed over time?
- Diagnoses have increased
- May be due to a change in diagnostic criteria
- More mild cases
78
What is autism?
- Highly heterogenous disorder
- Functions can be impaired or normal or improved
- Even those with severe intellectual disability usually preserve rote memory (musical/artistic abilities, ability to solve jigsaw puzzles)
79
What is a savant?
- Persons with intellectual disability who display amazing and specific cognitive or artistic abilities
- Ex. drawing, playing music, identifying prime numbers, etc
80
How often are people with ASD also savants?
- About 10-30% of people with ASD are savants
81
What are 3 genetic factors of autism spectrum disorder?
1 - It runs in families (5% chance that a sibling of a child with ASD will also have ASD)
2 - If one monozygotic twin has ASD, 60% chance that the other has ASD too
3 - Approximately 5% of cases of ASD explained by a single genetic mutation
82
What are some chromosomes that have been linked to autism?
- Loci on chromosomes 7 and 17
| - Possibly also on chromosomes 2, 5, 11, 15, 16 and X (affecting mostly males)
83
What are 4 genes that have been linked to ASD?
1 - A serotonin transporter on chromosome 17
2 - A TF on chromosome 7
3 - Several genes associated with glutamate action
4 - Neurexin 1 on chromosome 11
84
Is there a greater mutation load in males or females with ASD?
- Females
85
What are 4 de novo genes that are linked to autism?
1 - Chromatin/DNA modification/regulation
2 - Postsynaptic density
3 - Neuronal signaling/cytoskeleton
4 - Activity of many ion channels
86
What is one known environmental factor contributing to autism?
- Thalidomide (for morning sickness)
| - Leads to birth defects including autism
87
What are some mechanisms which are impaired in autism?
- Impaired face recognition
- > increased risk of Prosopagnosia
- > Difficulties recognizing facial emotions
- > Reduced activation of fusiform face area
- > Abnormal amygdala activation
- Reduced activation of mirror neurons system
88
Describe the 4 phases of brain growth in ASD?
1 - Slight prenatal brain undergrowth
2 - Rapid and large brain overgrowth at 6-14 months (predicts severity)
3 - Overall slow down in brain growth rate at age 1-5
4 - By adolescence brain size is no different from that of average healthy brains
89
Where is brain connectivity altered in ASD?
- Lower density in frontal lobe
| - Higher density in temporal and occipital lobe
90
How is oxytocin related to autism (3)?
1 - Children with ASD were shown to have reduced levels of circulating plasma oxytocin
2 - Children with ASD were shown to have a mutated form of the peptide
3 - Studies with OT administration show improvements in emotion recognition, eye contact, sterotypy, socialization and communication
91
What is the prevalence of Williams Syndrome?
- Occurs in 1 of ever 7500 people
92
What are some symptoms of Williams Syndrome?
- Intellectual disability
- Amazing language abilities
- Very poor spatial and drawing skills
- Preoccupation with a single subject/activity
- Sociable/empathetic
- Very good at recognizing faces
- Musical talent
- 'elfin' features
- Many health problems (mostly cardiac)
- Emotional immaturity
93
What is the genetic factor causing Williams Syndrome?
- Deletion in chromosome 7
- Gene for elastin (protein that gives elasticity to organs/tissues)
- 95% of people with Williams Syndrome lack the gene
94
What are some anatomical anomalies associated with Williams Syndrome?
- Small occipital and parietal cortex (poor spatial abilities)
- Normal frontal and temporal cortex (good speech abilities)
- Changes in limbic system (high emotionality)
95
There are 2 different mechanisms of neural migration: Glial-mediated migration and...
- Somal translocation
96
Where are new protoneurons produced in the embryo and what are two ways they migrate from this point of origin?
- Neurons are produced in the ventricular zone of the neural tube
- They can migrate by radial-glial cells or somal translocation
97
Design an experiment to assess whether one factor influences adult hippocampal neurogenesis. Be sure to indicate: the factor you intend to target and why, subject treatment condition, groups, expected outcome, and where specifically in the hippocampus you expect to see changes.
- Ex. enriched vs. unenriched environments
| - Enriched animals will have increased neurogenesis in the dentate gyrus
