lecture 20: development- synaptic rearrangements

Question 1

last and longest stage of development

Answer 1

Synaptic rearrangements and
critical periods during neural
development

Question 2

What’s special about the human
nervous system?

Answer 2

Adult human nervous system function is unique
Only animal with significant “culture” (but see “Almost Human, and
Sometimes Smarter” By JOHN NOBLE WILFORD, NY Times April 17, 2007
* Art, Music, Clothes, Religion, Architecture, etc
* Machines, Bridges, Lights, Planes, Trains, Cars, etc
* Exponential growth of scientific culture:
– Only animal to figure out how to leave planet (could lead to
immortality for the species)
– Only animal to figure out how to use “intelligent design” to modify
genetic heritage and overcome constraints natural selection
» (Both of these fundamental advances for planetary life
essentially occurred at the same instant, given the billion plus
year history of life on the planet)

Question 3

Strabismus or squint

Answer 3

misalignment of the eyes typically due to a weakness in
one or another extra-ocular muscle

Question 4

About half of children with untreated strabismus go on to develop

Answer 4

amblyopia

Question 5

amblyopia

Answer 5

a visual impairment akin to blindness but without any physical problem in the
retina or lens

Question 6

One effective treatment for amblyopia

Answer 6

to strengthen the muscles in the misaligned eye so it can be used for perception. This is done by patching the good eye to force the child to use the
misaligned one

Question 7

consequences of eye patch

Answer 7

patched eye (!) which can become nearly blind (ambylopia in the patched
eye)

Question 8

what accounts for the special features of our brains?

Answer 8

brain size (sperm whaile is 8k grams, man is 1500)

brain weight compared to body weight (but mouse is 3.2%, man is 2.1%)

relative to other animals with the same body size, our brains are really large (encephalization)

long gestation/brains have longer susceptibility to environmental influences

Question 9

neotony

Answer 9

slow development and retention of juvenile features

Question 10

developmental hypothesis

Answer 10

we acquire more information in our developmental stage because we stay young for longer

unique because of:
*Slow development
*Experience dependent neural development
*Obligate learner
*Culture-based behaviors
*“Intelligent” design of heritable traits (post-Darwin)
*Can leave planet (species immortality)

Question 11

brain circuitry does what as we mature

Answer 11

simplifies

Question 12

Hubel and Wiesel

Answer 12

Both trained as physicians
and both started as
postdoctoral fellows with
Stephen Kuffler (receptive
field properties of retinal
ganglion cells)
* They were both aware of the
interesting problem of
patching as a treatment for
strabismus
* Hubel developed the
Tungsten electrode (allowed
extracellular recording of
action potentials in cortical
and thalamic neurons)

Question 13

Tungsten electrode

Answer 13

(allowed extracellular recording of action potentials in cortical
and thalamic neurons)

Question 13

What is the basis for the shift in the ocular dominance histogram?

Answer 13

• Labeling with radioactive tracer
  from one eye reveals normally
  that the OCDs (in layer 4) are
  equal
• However unequal ocular
  dominance columns (odcs) in
  layer IV occur after monocular
  deprivation. Now the ocular
  dominance columns are wider
  for the open than the deprived
  eye
• This shift is due to changes in a
  developmental phenomenon
  known as ocular dominance
  segregation.

Question 14

The segregation ocular dominance columns (odcs)
during development

Answer 14

• At the time the visual cortex is susceptible to sensory
  deprivation its odcs are not fully formed- rather there
  appears to be considerable overlap between the regions
  occupied by the thalamocortical axons driven by the two
  eyes
• The end of the critical period coincides with the complete
  segregation of axons into non-overlapping ocdcs and raises
  the possibility that only when axons from the two eyes
  coincide can experience affect the outcome

Question 15

experiment with cats and ocular dominance columns in critical period

Answer 15

Thalamic axons driven by the
L & R eye overlap in layer 4
By 2 weeks of age (cat) there are small regions that are exclusively driven by axons from one eye or the other
By 3 weeks these monocular areas have gotten larger. By six weeks no areas of overlap still exist

Question 16

Summary of the
relation between
normal development
and the monocular
deprivation
experiments

Answer 16

The earlier the eye is
deprived the more profound
the loss of cortical area
occupied by the deprived
eye
* The territory held by the
deprived eye is the territory
it had exclusive control over
at the time of deprivation
* After complete segregation
deprivation has no effect
(think about the minimal
effects of not repairing a
cataract for even decades in
older adults)
* Thus this plasticity only
occurs during a “critical
period” of development

Question 17

Critical Periods

Answer 17

A “critical period” is a maturational stage in the lifespan of an organism
during which the nervous system is especially sensitive to certain
environmental stimuli
* More generally thought of as a period during someone’s development in
which a particular skill or characteristic is believed to be most readily
acquired.

Question 18

Hebb’s Postulate

Answer 18

Hebb says that “when the axon of a cell A is close enough to excite a B cell and takes part on its activation in a repetitive and persistent way, some type of growth process or metabolic change takes place in one or both cells, so that increases the efficiency of cell A in the activation of B “.

*neurons that “fire together wire together”
*neurons that
“fire out of synch, lose
their link”

Question 19

Alternating eye patching
experiment in
development

Answer 19

(both eyes never used at the same time) wipes out binocular
neurons in cortex in later
life

Question 20

synapse elimination

Answer 20

more axons innervate each target cell in
young animals than later (convergence decreases with
age)

Question 21

Synaptic basis for the critical period

Answer 21

evident in the development
of the neuromuscular junction which undergoes a change from
multiple Innervation in early life to single innervation

Question 22

Synaptic site takeover by the remaining axon

Answer 22

*Thus axons compete
for postynaptic sites
*Remaining axon takes
over sites vacated by
losers

Question 23

Final network is result of

Answer 23

massive branch pruning
during development

Question 24

Imprinting

Answer 24

Explained the normal
following behavior of
goslings
* Showed that goslings
imprinted on first moving
object no matter what it
is (dog, ball, box, Konrad)
* Showed that effect is
particularly strong only
the first day or two of
postnatal life
* Also there is auditory
imprinting

Question 25

Imprinting

Answer 25

Explained the normal
following behavior of
goslings
* Showed that goslings
imprinted on first moving
object no matter what it
is (dog, ball, box, Konrad)
* Showed that effect is
particularly strong only
the first day or two of
postnatal life
* Also there is auditory
imprinting

Question 26

Reactive Attachment Disorder

Answer 26

Developmentally inappropriate social relations.
Either:
* Failure to initiate or respond to social interactions Or
* Indiscriminate sociability, excessive familiarity with
strangers

Question 27

Plasticity

Answer 27

the nervous system, usually via synaptic connections, to change and
adapt to new situations

Question 28

Hebb’s postulate

Answer 28

the idea that the timing of the presynaptic and postsynaptic action
potentials can alter the synaptic strength. Summarized as Neurons that fire together, wire
together and Neurons out of synch, loose their link

Question 29

Critical period

Answer 29

a developmental period during which the nervous system is particularly
sensitive to the effects of experience. Experience can permanently alter performance, behavior
and /or neural circuits. The precise timing of the critical period depends on which circuit in
which brain region is being altered. Usually there is little plasticity either before the beginning or
after the closure of the critical period

Question 30

Synapse elimination (pruning)

Answer 30

there is an excess of synaptic connections (and even an
excess of neurons) during development. Following Hebb’s postulate, synapses that are more
active are strengthened, and synapses that are less active are weakened and ultimately
pruned. Synaptic elimination involves the removal of both the presynaptic terminal and
postsynaptic density/spine

Question 31

Spontaneous neuronal activity

Answer 31

firing of neurons in the absences of environmental stimuli.
Often occurs as oscillations or waves of activity that propagate across the brain region.
In the developing eye
(before birth/eye
opening), retinal waves of
spontaneously active
RGCs and amacrine cells
sweep across the retina,
activating nearby RGCs
concurrently. By contrast,
the activity of RGCs at
different sides of the
retina, or from the other
eye, are uncorrelated.
This correlated activity of
the RGCs (the output
neurons of the eye) helps
maintain the retinotopic
map in the thalamus and
visual cortex, and drives
the segregation of their
axons so that the layers
of the LGN receive input
from only one eye and
subsequently neurons in
layer 4 of V1 are
monocular

Question 32

Ocular dominance

Answer 32

the preference for receiving and/or representing visual input from one eye
over the other eye. Neurons in layer 4 of V1 in primates, cats and some other mammals, receive input from just one eye. Neurons “beyond” layer 4, may be binocular (see diagram to
the right, of the histogram of neuronal responses in layers 2/3 of V1 in control animals on the left column).

During the critical period for ocular dominance plasticity, the responses of neurons can shift so that following experience manipulation (closing one eye) the responses shift so more neurons respond to the open eye. The histograms on the figure on the previous page show the different
responses of neurons found in cat primary visual cortex after monocular deprivation was performed either in adulthood (left histogram) or during the critical period (right histogram).
When monocular deprivation was performed during the critical period, the responses of the neurons shifted, so that the majority of neurons responded only to light to the open eye (“ocular dominance group 7), whereas neurons continued to respond binocularly (ocular
dominance group 4) or to light in the previously closed eye or the open eye.

Question 33

Ocular dominance columns

Answer 33

in primary visual cortex of primates and some other mammals,
cells in the same vertical column share the same ocular dominance, thus producing ocular
dominance columns

Question 34

Amblyopia

Answer 34

diminished visual acuity (typically just in one eye) as a result of the failure to
establish appropriate visual connections during development (during the critical period). Often
caused by strabismus, a misalignment of the two eyes, or by the inability of one eye to focus. Vision to the eye itself can be normal, but the brain favors the other eye

Question 35

Monocular deprivation

Answer 35

experimental procedure where one eye of an animal is patched or sutured to eliminate visual input to that eye. Binocular deprivation would involve either patching
both eyes, or placing the animal in the dark (dark rearing). Both would be considered forms of
sensory deprivation

Question 36

1. Define critical periods and link changes in neurons to this phenomenon.

Question 37

Describe how changes in convergence and divergence lead to synaptic rearrangements in
the developing nervous system as occurs in the neuromuscular system.

Question 38

3. Use Hebb’s postulate to explain how monocular deprivation during the critical period changes ocular dominance columns and impacts the responses of neurons in the visual
   system

Question 39

4. Discuss how spontaneous activity and developmental misalignment of the two eyes lead to ocular dominance columns

Question 40

5. Link critical periods to socialization and Reactive Attachment Disorder.