DEVELOPMENT OF THE NERVOUS SYSTEM:Cell competition, Synaptic Rearrangement

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Neurological Basis of Behavior (PSY - 610)

Lesson20

DEVELOPMENT OF THE NERVOUS SYSTEM

Objective

To familiarize the students with:

· Various stages of neuronal development.

· Development of the brain: from the fertilization to the various developmental stages in-utero,

and postnatally.

· Cell differtiation, determination migration, (inside-out), cell competition, Cell death, growth

Cones, Nerve growth Factor and its role, Influences in growth and development of the brain

If all cells keep growing, connection expanding, how does it stop- who controls development,

differentiation, migration As research ahs shown this is a Self regulatory process and the cell number in

early development is 40 times more than the normal adult brain, what happens how do cells reduce in

size?

Cell competition: Cells compete for limited resources; some have to die so others can live there is fight

for,

a) Life preserving factors NGF and Tropic factors from the targets site are limited

b) There are few sites available for the millions of neurons

Cell death: some cells will die off and only the fittest would survive. Cells would die off

a) If connections were not formed

b) If the neurons reach the sites but fail to send out projections to appropriate targets

c) And if cells do reach but are unable to compete for post synaptic space

d) If the NGF is more than or less than required.

Synaptic Rearrangement:

Cells sprout and make a large number of connections eventually these are refined and made more

precise. Is cell rearrangement possible? Yes, weaker or incorrectly placed connections or cells die and

leave space for others. Synaptic rearrangement makes for more efficient systems. This ensures that a

specific and selective system for transmission remains functional

Important for the migration and growth of the developing neurons are the

a) Radial Glials which form the transport system to take the neurons from the inner ventricular zone

where they are born to the sites where they would eventually form the brain and

b) The Nerve Growth factor which is important for Axonal Growth cones and for cells to locate

themselves and connect.

Since there are a huge number of cells and limited resources and locations, cells compete for these (Cell

Competition) and those who cannot do so die (Cell Death). Therefore forming of connections is

important for survival and each cell forms more synapses then needed (to compete with others). These

connections are reformed later to make the system more efficient, also depending on the stimulation

received

Neurological Basis of Behavior (PSY - 610)

Destinations for Migration:

The question that how do the newborn cells know where to go, how are their destinations for migration

"decided" is an interesting and complex one. Several hypothesis have been developed to explain this

phenomenon

The Chemoaffinity hypothesis:

This theory is based on the work of Sperry and his colleagues on the regeneration of ganglionic neurons

of retina. They cut the optic nerves and rotated the eyeballs of frogs by 180 degrees. They report that

after regeneration when tested it was found that visual world rotates at same angles. Sperry then

hypothesized that chemicals to attract axons are released by the growing postsynaptic surface, and axons

attracted to the "label: during neurulation and migration and well as during regeneration (if these are

damaged during early period).There is strong evidence that a) in vitro, when growing axons are laid

with tissue in the Petri dish, axons move to connect to their targets (there is no signaling from the other

parts of the brain in the Petri dish!) b) There are chemical signals which attract or repel growth cones

from the extracellular tissue. However, this hypothesis cannot explain extra growth with transplanted

organs areas such as the experiments by Whitelaw and Hollyday (1983) where they added an extra thigh

to the two normal chick legs, (where the chick's legs had two thighs instead of one!). Where did the 2nd

thigh get its nerves from (from the calf, or from the 1st thigh?). Secondly, this does not explain why and

how do some axons find their way to same targets in every species using a roundabout route, not go by

the shortest routes directly (!). Lastly if this is genetically programmed then there should be genes in

each body cell to produce and release its own chemicals, this is not possible!

Therefore we go for the next possible hypothesis and see if that one is tenable

The Blueprint Hypothesis:

This hypothesis states that the undeveloped Nervous system has a blueprint in the form of specific

chemical, biological/mechanical pathways which the growing axons would follow to get to their

destination. These pathways are laid out by the Pioneer Growth Cones, which are the first growth cones

to travel on the specific radial glial and the route. These pioneer growth cones do so through their

interaction with the CAMS (it's like the blind feeling the walls along the way). Interestingly the axons

are also growing while traveling. This is called fasciculation. If these pioneer axons are destroyed the

following axons get lost and go to different destinations! However, this hypothesis cannot explain in

vitro travels (no radials) as there are no pioneer axons there. It also cannot explain how neurons in vivo

still reach correct destination even when starting points changed In experiments on transected and then

inverted spinal cord of chicks, the axons were able to reach their correct target muscles, inspite of

starting from an inverted location.

Since this hypothesis also has not been able to explain the migratory programming of the neurons, we

move to the next hypothesis

Topographic gradient hypothesis:

This hypothesis proposes that cells follow their topographic gradients or locations. Though Neurons

develop in topographic layers, they maintain their relationships with topographically different groups of

neurons. For example, the relationship of the optic tectum in the brain with retina: cells growing out of

an original sheet of cell bodies retain their relationships as they grow in different locations even if they

have migrated. There are in the same point to point relationship (held previously on the sheet: whether

up down or left-right gradient)

Neurological Basis of Behavior (PSY - 610)

Evidence from retina and tectum cells connections, when mapped show that cells are maintaining their

earlier relationships. There is evidence that this hypothesis has more strong evidence in favor of it.

This is an interesting piece of the puzzle that we in the developmental neurosciences are still trying to

unravel. There are other mysteries such as what is the role of the environment if the cells are

programmed. We would discuss it in the next lecture

References

1. Kalat J.W (1998) Biological Psychology Brooks/ Cole Publishing

2. Carlson N.R. (2005) Foundations of Physiological Psychology Allyn and Bacon, Boston

3. Pinel, John P.J. (2003) Biopsychology (5th edition) Allyn and Bacon Singapore

4 Bloom F, Nelson and Lazerson (2001), Behavioral Neuroscience: Brain, Mind and Behaviors (3rd

edition) Worth Publishers New York

5. Bridgeman, B (1988) The Biology of Behaviour and Mind. John Wiley and Sons New York

6. Brown,T.S. and Wallace. (1980) P.M Physiological Psychology

Academic Press New York

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