lecture 20: development- synaptic rearrangements Flashcards
last and longest stage of development
Synaptic rearrangements and
critical periods during neural
development
What’s special about the human
nervous system?
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)
Strabismus or squint
misalignment of the eyes typically due to a weakness in
one or another extra-ocular muscle
About half of children with untreated strabismus go on to develop
amblyopia
amblyopia
a visual impairment akin to blindness but without any physical problem in the
retina or lens
One effective treatment for amblyopia
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
consequences of eye patch
patched eye (!) which can become nearly blind (ambylopia in the patched
eye)
what accounts for the special features of our brains?
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
neotony
slow development and retention of juvenile features
developmental hypothesis
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)
brain circuitry does what as we mature
simplifies
Hubel and Wiesel
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)
Tungsten electrode
(allowed extracellular recording of action potentials in cortical
and thalamic neurons)
What is the basis for the shift in the ocular dominance histogram?
- 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.
The segregation ocular dominance columns (odcs)
during development
- 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
experiment with cats and ocular dominance columns in critical period
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
Summary of the
relation between
normal development
and the monocular
deprivation
experiments
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
Critical Periods
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.
Hebb’s Postulate
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”
Alternating eye patching
experiment in
development
(both eyes never used at the same time) wipes out binocular
neurons in cortex in later
life
synapse elimination
more axons innervate each target cell in
young animals than later (convergence decreases with
age)
Synaptic basis for the critical period
evident in the development
of the neuromuscular junction which undergoes a change from
multiple Innervation in early life to single innervation
Synaptic site takeover by the remaining axon
*Thus axons compete
for postynaptic sites
*Remaining axon takes
over sites vacated by
losers
Final network is result of
massive branch pruning
during development
Imprinting
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
Imprinting
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
Reactive Attachment Disorder
Developmentally inappropriate social relations.
Either:
* Failure to initiate or respond to social interactions Or
* Indiscriminate sociability, excessive familiarity with
strangers
Plasticity
the nervous system, usually via synaptic connections, to change and
adapt to new situations
Hebb’s postulate
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
Critical period
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
Synapse elimination (pruning)
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
Spontaneous neuronal activity
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
Ocular dominance
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.
Ocular dominance columns
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
Amblyopia
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
Monocular deprivation
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
- Define critical periods and link changes in neurons to this phenomenon.
Describe how changes in convergence and divergence lead to synaptic rearrangements in
the developing nervous system as occurs in the neuromuscular system.
- 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
- Discuss how spontaneous activity and developmental misalignment of the two eyes lead to ocular dominance columns
- Link critical periods to socialization and Reactive Attachment Disorder.
