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DEVELOPMENT OF THE NERVOUS SYSTEM:Cell competition, Synaptic Rearrangement

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Neurological Basis of Behavior (PSY - 610)
VU
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
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Neurological Basis of Behavior (PSY - 610)
VU
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)
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Neurological Basis of Behavior (PSY - 610)
VU
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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Table of Contents:
  1. INTRODUCTION:Descriptive, Experimental and/ or Natural Studies
  2. BRIEF HISTORICAL REVIEW:Roots of Behavioural Neurosciences
  3. SUB-SPECIALIZATIONS WITHIN THE BEHAVIORAL NEUROSCIENCES
  4. RESEARCH IN BEHAVIOURAL NEUROSCIENCES:Animal Subjects, Experimental Method
  5. EVOLUTIONARY AND GENETIC BASIS OF BEHAVIOUR:Species specific
  6. EVOLUTIONARY AND GENETIC BASIS OF BEHAVIOUR:Decent With Modification
  7. EVOLUTIONARY AND GENETIC BASIS OF BEHAVIOUR:Stereoscopic vision
  8. GENES AND EXPERIENCE:Fixed Pattern, Proteins, Genotype, Phenotypic
  9. GENES AND EXPERIENCE:Mendelian Genetics, DNA, Sex Influenced Traits
  10. GENES AND EXPERIENCE:Genetic Basis of behavior, In breeding
  11. GENES AND EXPERIENCE:Hybrid vigor, Chromosomal Abnormalities
  12. GENES AND EXPERIENCE:Behavioral Characteristics, Alcoholism
  13. RESEARCH METHODS AND TECHNIQUES OF ASSESSMENT OF BRAIN FUNCTION
  14. RESEARCH METHODS AND TECHNIQUES OF ASSESSMENT OF BRAIN FUNCTION:Activating brain
  15. RESEARCH METHODS AND TECHNIQUES OF ASSESSMENT OF BRAIN FUNCTION:Macro electrodes
  16. RESEARCH METHODS AND TECHNIQUES OF ASSESSMENT OF BRAIN FUNCTION:Water Mazes.
  17. DEVELOPMENT OF THE NERVOUS SYSTEM:Operation Head Start
  18. DEVELOPMENT OF THE NERVOUS SYSTEM:Teratology studies, Aristotle
  19. DEVELOPMENT OF THE NERVOUS SYSTEM:Stages of development, Neurulation
  20. DEVELOPMENT OF THE NERVOUS SYSTEM:Cell competition, Synaptic Rearrangement
  21. DEVELOPMENT OF THE NERVOUS SYSTEM:The issues still remain
  22. DEVELOPMENT OF THE NERVOUS SYSTEM:Post natal
  23. DEVELOPMENT OF THE NERVOUS SYSTEM:Oxygen level
  24. Basic Neuroanatomy:Brain and spinal cord, Glial cells, Oligodendrocytes
  25. Basic Neuroanatomy:Neuron Structure, Cell Soma, Cytoplasm, Nucleolus
  26. Basic Neuroanatomy:Control of molecules, Electrical charges, Proximal-distal
  27. Basic Neuroanatomy:Telencephalon, Mesencephalon. Myelencephalon
  28. Basic Neuroanatomy:Tegmentum, Substantia Nigra, MID BRAIN areas
  29. Basic Neuroanatomy:Diencephalon, Hypothalmus, Telencephalon, Frontal Lobe
  30. Basic Neurochemistry:Neurochemicals, Neuromodulator, Synaptic cleft
  31. Basic Neurochemistry:Changes in ionic gates, The direct method, Methods of Locating NT
  32. Basic Neurochemistry:Major Neurotransmitters, Mesolimbic, Metabolic degradation
  33. Basic Neurochemistry:Norepinephrine/ Noradrenaline, NA synthesis, Noadrenergic Pathways
  34. Basic Neurochemistry:NA and Feeding, NE and self stimulation: ICS
  35. Basic Neurochemistry:5HT and Behaviors, Serotonin and sleep, Other behaviours
  36. Basic Neurochemistry:ACH and Behaviors, Arousal, Drinking, Sham rage and attack
  37. Brain and Motivational States:Homeostasis, Temperature Regulation, Ectotherms
  38. Brain and Motivational States:Biological Rhythms, Circadian rhythms, Hunger/Feeding
  39. Brain and Motivational States:Gastric factors, Lipostatic theory, Neural Control of feeding
  40. Brain and Motivational States:Resting metabolic state, Individual differences
  41. Brain and Motivational States:Sleep and Dreams, Characteristics of sleep
  42. Higher Order Brain functions:Brain correlates, Language, Speech Comprehension
  43. Higher Order Brain functions:Aphasia and Dyslexia, Aphasias related to speech
  44. Higher Order Brain Functions:Principle of Mass Action, Long-term memory
  45. Higher Order Brain Functions:Brain correlates, Handedness, Frontal lobe