1
Q
1.
The Human Brain:
List 3 statments
A
The human brain weighs 1.3 kg and is made up of 100 billion neurons (85 billion??) with 100 trillion connections.
- It is thought to have ten times a many glial cells as neurons.
- It is one of the most the most complex structures in the known universe.
2
Q
- The human brain may be estraordinary but is it in absolute terms?
A
NO:
During the course of our development, humans build big brains, but there are animals that develop bigger brains than ours:
- The elephant has a brain 3.5 bigger than human’s.
- The Blue Whale’s brain is 5 times bigger than ours (Passingham 1982).
3
Q
3.
What is the Encephalisation Quotient (EQ)?
A
A measure of relative brain size defined as the ratio between actual brain mass and predicted brain mass for an animal of a given size, which is hypothesized to be a rough estimate of the intelligence or cognition of the animal.
Actual brain size
___________________________________________Average brain size for a mammal of that body weight
Human EQ = 7.5. Hence, we have a brain 7.5 times bigger than one would expect of an average mammal of our body size (Jerison 1973)
4
Q
4.
Primates as an Order have relatively bigger EQs than other types of animals.
A
5
Q
5.
Brain weight /body weight for primates?
A
Our brain is 3.1 times as big as one would expect for an average primate of our body size.
- Thus, in absolute terms humans do not build the biggest brains on the planet during the course of development. Nevertheless, it is a much bigger brain than one would expect for an average mammal, or even primate, of our body size.
- Our brain size has a profound effect upon all aspects of our development across our lifespan.
6
Q
6
Life Cycles of Primates
A
This is based on hunter gatherers (H-G) as with modern medicine lifespans have been extended extensively.
- P = Prosimians (before money - Lemur etc)
- OWM = Old World Monkey
- LA =Lesser Apes (Gibbons)
- GA = Great Apes (closer genetically)
- HG = Hunter Gatherers
7
Q
7.
Discuss big body development.
A
- In general, animals with big bodies develop slowly.
- However, even when we allow for body size primates develop particularly slowly compared to other mammals.
- The rate of development is correlated with adult brain size.
8
Q
8.
Length of gestation in primates:
A
The length of gestation is determined by the size of brain that needs to be built. However, by such logic, our gestation should last 3 times longer than a chimpanzee’s: i.e., 714 days or 24 months!
Why is human gestation cut short?
9
Q
9.
List brain capacity at birth in %:
- Rhesus macaque
- Chimpanzee
- Human beings
A
Brain capacity at birth (compared to adult)
- Rhesus macaque 60%
- Chimpanzee 46%
- Human beings 23% (less than a 1/4 of adul rate!)
Undeveloped young is a primate feature.
10
Q
10.
In _______________ continues to grow at the foetal rate for _______________ (Bogin 1997). By 3 year of age it is at __ adult capacity and _____ by five years of age (Dekaban & Sadowsky 1978)
A
In humans the brain continues to grow at the foetal rate for two years after birth (Bogin 1997). By 3 year of age it is at 80% adult capacity and 90% by five years of age (Dekaban & Sadowsky 1978)
11
Q
11.
What is human brain weight at:
- Neborn
- Age 3
- Age 5
A
- Newborn’s brain: about 25% of adult size
- Age 3: about 80% of adult size
- Age 5: about 90% of adult size
12
Q
12.
Is it only brain size that is underdeveloped in humans?
A
• It is not just in terms of brain size that we seem underdeveloped at birth:
- Human beings seem to be born before they are fully developed. Our bones do not fully calcify until one year after birth (born in a foetal state)
- Rhesus macaques have a gestation period of 24 weeks, their bones have fully calcified by the 18th week of gestation (way before birth)
13
Q
13.
What does bipedal locomotion make particulalry difficult?
A
- Humans develop a very large brain and yet because of bipedal locomotion the female of the species has a long and narrow birth canal.
- Hence rather than waiting, we push our babies out early.
Img: Human (above); chimpanzee (below)
14
Q
14.
The fontanelles:
Size of neonate’s head relative to the pelvic outlet
A
- At the points where the plates of the skull meet are little gaps called fontanelles. The anterior fontanelle in newborn humans is a diamond shaped aperture of an inch in diameter. It allows the bones to slide over each other slightly reducing the dimensions of the cranium during birth.
- The cranial plates do not grow together until about 2 year of age.
- There must have been intensive selection pressure for large brain in humans, which seems to have started early…
15
Q
15.
(Alemseged et al 2006) Australopithecus afarensis
A
The 3.5Myrs old skull of an Australopithecus afarensis child estimated to be 3 years old (Alemseged et al 2006).
- Brain size estimated at 330 cubic centimetres, about the same as a 3 year-old chimpanzee.
- However, compared to the adult values of its species, the Dikika baby had formed only between 63 and 88% of the adult brain size, which is lower than that of a 3 year only chimpanzees whereby over 90% of the brain is formed.
- This relatively slow brain growth observed in A. afarensis is slightly closer to that of humans, pointing to a possible behavioural shift in this species (Science Daily 2006).
16
Q
16
One cell to trillions:
What is the zygote?
A
- All human life starts with one cell: the fertilized egg or zygote. How can a single cell be responsible for such wondrous complexity?
- A zygote contains the blueprint for our brains and body. Each is comprised of 23 pairs of chromosomes. Each chromosome is packed full of long strands of DNA, which can be divided into functional units called genes.
17
Q
17.
Gene-environment interaction
A
- Although brain development is “gene-driven”, there is also a vital interaction with environment factors.
- All aspects of development are the result of an interaction between genes and the environment. The development of the brain constitutes an interplay between biologically inherited processes and environmental influences (Smith et al. 2003).
18
Q
18
What is the neural groove?
A
The neural groove is a shallow median groove of the neural plate between the neural folds of an embryo.
This becomes the neural tube (27 days) and is the embryo’s precursor to the central nervous system (CNS)
19
Q
19.
What is Encephalisation?
A
- In humans, the cephalic (head) portions of the neural tube grow tremendously and this disproportionate growth is referred to as “encephalisation”.
- Even before closure of neural tube is complete, the cephalic part of the neural tube differentiates into 3 primary spaces, or ventricles that will become the CNS.
- Three clear sections as early as 26 days
- forebrain (prosencephalon)
- midbrain (mesencephalon)
- hindbrain (rhombencephalon)
20
Q
20.
EVENTUAL ADULT BRAIN STRUCTURES
A
- Telencephalon -> cortex
- Denencephalon -> thalamus and hypothalmus
- Mesencephalon -> midbrain
- Metencephlon -> pons, cerebellum
- Mylencephalon -> medulla
Increasing complexity
21
Q
21.
– One of the most sensitive periods in brain development occurs at the very beginning, when the neural tube is closing.
What is
- Anencephaly
- Spina bifida
A
- Anencephaly literally means a lack of cerebralcortex. The neural tube fails to close at anterior (or front) end and babies are born with no brain. The condition is always fatal.
- Spina bifida is caused by a failure of the neural tube to close properly at posterior (rear) end so that part of the spinal cord develops outside the spine, rendering it vulnerable to damage. The condition has varying outcomes.
22
Q
22.
Human brain vs. others?
A
- 25 days human CNS like worm
- 40-50 days like vertebrate
- 100 days like mammalian
- 5 months, primate uniquely human: vast expansion forebrain and cerebral cortex
23
Q
23.
Describe the humna brain at 5 weeks:
A
After the first five weeks, the brain’s gross features are formed by growth and flexion (or bending) of the neural tube’s anterior (front) portions. The result is a cerebral cortex that envelops the subcortical and brainstem structures that started out in line with the cortex along the neural tube. The final gross structural form are the product of continued cortical enlargement and folding.
24
Q
24.
What are the stages of brain cell development?
A
- Birth
- Migration
- Differentiation and
- Maturation
- Synaptogenesis
- Death (synaptic pruning and neuronal)
- Rearrangement
- Mylenation
25
25.
## Footnote
Stage 1: **Cell Birth**
* Neurones are the information super highways of the brain.
* By 7 months of human gestation nearly all of the adult number of 200? billion neurones have been produced.
* To produce this number, about 500,000 neurones must be born _PER MINUTE_ at the peak of brain development.
* Yet the newborn brain is less than a quarter the adult brain volume or weight. Where do you think the extra volume comes from? (dendrites and synapses and glial cells)
26
26
## Footnote
Postnatal brain volume comes from:
►Synaptogenesis - formation of new synapses
►Myelination of many axons (glial cells)
►Increased branching of dendrites
27
27. Stage 1: cell birth
## Footnote
Neuron and Glial Formation:
* The neural tube is the “nursery”for the brain and its cells. The cells that line the neural tube are _neural stem cells_. Stem cells line the ventricles – the **_ventricular zone_**. These cells have an extensive capacity for renewal. They give rise to progenitor or precursor cells.
28
28.
List some stages of cell development
All cells start out the same:
1. Stem renewal
2. Progenitors or precursors produced
3. Neuroblasts (a dividing cell that will develop into a neurono) or glioblasts produced
4. Neuron or glial differentiation
29
29.
## Footnote
Stem cell switch points: **Neuroblast to glioblast** production
* At early stages, a stem cell generates neuroblasts. Later, it undergoes a specific “switch point” at which it changes from making neurons to making **_glia._**
30
30.
## Footnote
Stage 2: Cell Migration
Neurons migrate from the ventricular zone to the surface of the cortex along peculiar cells called radial glia.
https://www.youtube.com/watch?v=ZRF-gKZHINk
(neuronal migration, 11 seconds)
31
31.
## Footnote
**What are Radial glia?**
**Radial glia** transform into astrocytes in the adult brain.
Astrocytes perform many functions including
providing structural support, insulation, and carrying
nutrients.
32
32
Stage 2: **Growth Cones**
**_Growth cones_** dynamically crawl forward dragging the rest of the axon behind them. Their extension is controlled by cues in their outside environment that ultimately direct them toward their appropriate synaptic targets.
The fine threadlike extensions are **filopodia**, which find adhesive surfaces and pull the growth cone and therefore the growing axon in a particular direction.
33
33.
How is the cortex built?
Cortex built from the i_nside out_
* First neurons lie in the deepest cortical layers, whereas the last to migrate push through them to the cortical surface (building up the layer of an onion).
* Six cortical layers are constructed, but at different rates in different parts of the brain (e.g. Nowakowski & Hayes 1999; Chugani et al. 1987; Huttenlocher in Johnson 2002).
34
34.
## Footnote
Describe disruption of cortical development
* Anything that disrupts the normal timeline of cortical construction has profound effects on cortical formation.
* Neuronal migration is severely disrupted by chronic maternal alcohol abuse resulting in fetal alcohol syndrome with cognitive, emotion and physical disabilities.
35
35.
## Footnote
Stage 3: **Cell Differentiation**
* For the first 5-6 weeks cell division in the ventricular zone is symmetrical – every cell is the same (a precursor cell)
* From 5-6 weeks onwards there is asymmetrical division
– cell divides, 1 migrates, 1 remains in ventricular zone; cycle repeats
36
36.
## Footnote
What is **cell determination?**
* The type of cell a migratory neuron becomes and the location it ends in is determined by **gestational age at cell division.**
* _Neurons_ born at the _same age_ migrate to prespecified cortical layer regardless of whether they remain in the donor (their original cellular environment) or are transplanted to an older host (R)
* This is likely why development is so critical at these stages of growth
37
37.
## Footnote
Stage 4: **Cell Maturation**
* Once a neuron has reached its final position, it grows out its axons and dendrites.
* “**Exuberant growth**”: transient innervation of cells / areas not connected in adult
* divergence: 1 cell innervates more cells than it does in adult. Extra connections eliminatedthrough development.
38
38.
## Footnote
Stage 5: Define **Synaptogenesis**
**What are target cells?**
Axons (with growth cones on end) form a synapse with other neurons or tissue (e.g. muscle)
**Target cells** release a chemical that creates a gradient (dots or crosses in diagrams) around them. _Growth cones_ orient to and follow the _gradient_ to the cells. The extensions visible in the far right picture are growing out of a sensory ganglion (left) toward their normal target tissue (right).
39
39.
## Footnote
Stage 6: **Neuronal Death**
* Between 40% and 75% of all neurons born in embryonic and fetal development do not survive.
* They fail to make optimal synapses.
* Use it or lose it!
40
40.
## Footnote
Neuronal death leads to Stage 7 - **Synaptic**
**rearrangement**
1. Release and uptake of neurotrophic factors
2. Neurons receiving insufficient neurotropic factor die
3. Axonal processes compete for limited neurotrophic factor
41
41.
## Footnote
What is the likely role of **neurotrophic factor**?
* Active synapses likely take up neurotrophic factor that maintains the synapse
* Inactive synapses get too little trophic factor to remain stable
42
42.
## Footnote
Waht is Synesthesia?
• Synesthesia is a neurological condition in which stimulation of one sensory or cognitive pathway leads to automatic, involuntary experiences in a second sensory or cognitive pathway. There are many kinds, e.g.:
– _Color graphemic synesthesia_, letters or numbers are perceived as inherently colored
– _Visual motion → sound synesthesia_ involves hearing sounds in response to visual motion and flicker
There is a hypothesis that at least some kinds of synesthesia is due to an unusual pattern or cell death or dendritic pruning during development
43
43.
## Footnote
Stage **8: Myelination**
Material that forms a layer, the myelin sheath, usually around only the axon of a neuron.
It is essential for the proper functioning of the nervous system. It is an outgrowth of a type of glial cell.
Myelination Lasts for up to _30 Years_
44
44.
What are the influence of genes in brain development?
At least half of our genome is devoted to producing our brain. For the nine months of intrauterine life and for a short but indeterminate postnatal period, brain growth and development will be largely genetically determined. Recent advances in molecular genetics have identified numerous genes that are expressed in the developing brain and that control **CNS** development.
45
45.
## Footnote
Epigenetic (environmental) factors -
– involved from beginning
– play increasingly important role
– cell death, synaptic shedding, synaptic rearrangement and myelination all take place during and after foetal development. The number and kinds of connections that are established and survive are related to environmental input.
The idea of being simply dedermined by genes is not perhpas a good model - the environment plays a crucial role of turing genes on and off.
46
46.
## Footnote
Plasticity - is it always active?
**Postnatal development**
* There is some neuronal plasticity (after all cell death, synaptic shedding, synaptic rearrangement and myelination all start before but continue after birth)
* this plasticity is limited. Cells are not free to migrate to new areas, or to make large changes in long-distance connectivity
**Sensitive periods**
* extrinsic influences can alter brain organisation
* once sensitive periods pass lack of plasticity
**Adult CNS damage**
* irreversible
* neurons don’t regenerate damaged connections
* lost neurons not replaced (although Eriksson et al. 1998 found new neurons produced in the adult hippocampus)
47
47.
## Footnote
Postnatal development: Synaptic shedding
The degree and exact pattern of synaptic shedding is influenced by environmental input.
48
48.
Describe the study by **Diamond et al (1987)**.
Rats kept in enriched physical and social environment had more dendritic connections (9,400 compared to 7,600) that were thicker than control rats kept in impoverished environments.
49
49.
## Footnote
Sensitive periods: Environmental
impoverishment of Romanian orphan
• 1989: Fall of Communist regime
– 1000s of severely deprived children from state orphanages
– Many adopted in USA, Canada, UK, other European countries
• Investigation of consequences of deprivation, ‘sensitive periods’ in cognitive, language, social development
50
50.
## Footnote
Romanian Orphans - is there a sensitive age to cognitive imparment? Who will recover in more enriched environments?
►Those children adopted at less than _4 month_s of age were found to have an IQ of 98 at 4.5 years
►Those adopted at a median of 19 months had an IQ of 90 at 4.5
►Age matched Canadian control children had an IQ of 109 (at 4.5 years)
51
51.
## Footnote
Sensitive Periods: Weisel & Hubel (1965) - What was the study?
One of a kitten’s eyes was sown shut for the first 4-6 weeks of life. After the stitches were taken out the cells that would usually process visual information were unable to do so. After this sensitive period sewing the eyes shut has no effect. Visual development needs environmental input during a _sensitive period_ of _neural development._
52
52.
## Footnote
Visual deprivation in human development?
• Amblyopia (lazy eye) – vision deficiency in an eye that is otherwise normal. There are several causes such as a drooping eyelid or one eye turned inward (strabismus)
– requires surgical correction
– if uncorrected by 7-8 years, pattern vision is almost completely suppressed and individuals can be functionally blind in the affected eye
– no adaptation with subsequent correction
53
53.
## Footnote
Plasticity in the _adult brain?_
• Adult humans learn … learning involves changes in synaptic weights between neurons. So, there must be functional plasticity in the adult brain.
› How great is the change?
› How much is there cortical reorganisation?
54
54.
## Footnote
New neurons in the adult **_hippocampus_**
* **Eriksson et al. (1998)** found that new neurons were produced in the adult hippocampus.
* **Maguire et al. (2000)** found that London taxi drivers who had completed “The Knowledge” had enlarged hippocampuses compared to non-taxi drivers. It is impossible to tell whether the enlargement was principally due to dendritic proliferation or neurogenesis.
55
55.
How does experience modify cortical motor maps?
* Mike Merzenich and his colleagues have shown how cortical sensory and motor maps can be modified with experience.
* The somatosensory map is a point by point representation of sensory areas
* More sensitive areas are larger & more densely packed
* Adjacent areas in body are adjacent on somatosensory map
56
56.
What have studies on monkeys hands shown?
* Manipulate peripheral receptors change somatosensory maps
* Over a few months, adjacent area takes over function
* Also seen in visual and auditory cortex
e.g. Gilbert & Wiesel 1990;
Recanzone et al. 1993;
Merzenich & Kaas 1995
57
57
What has been found with an amputation of the arm?
* Male adult, left arm amputated
* When areas of his face were touched with a Q tip, he reported sensations in various areas of the left hand and arm. This is different to phantom limb sensation - where you feel as if your arm is still there independently of any stimulation.
* Essentially there was now a map of the young man’s hand on his face. This is because the areas of the somatosensory cortex responsible for the left hand/arm had been taken over by those adjacent areas – the head/face. There is now overlap such that sensation can be triggered from the ‘new’ source to the older, now nonexisting (amputated) limb.
58
58.
Some conclusions....
* Developmental neurobiology is a rapidly growing field of research
* The brain has a profound effect on the pattern of human development across the lifespan
* There is a precise timing of cortical development
* The brain undergoes exuberant proliferation and then fine tunes its connections
* There is some plasticity, particularly in prenatal brain during sensitive periods and some plasticity is now known to exist in adults
MMB-Biological Aspects of Brain Function
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