Developmental Neuroscience
Fall 2002

Everyone begins with two cells, an egg & sperm, which fuse. About 2 weeks after fertilization, the top of embryo folds in and closes forming the neural tube (Figure 7.8). The neural tube will develop into the brain and spinal cord. The hole inside the neural tube will become the ventricles of the brain and the central canal of the spinal cord.
 

There are a group of cells dorsal to the neural tube called the neural crest (Figure 7.8). The neural crest will develop into the peripheral nervous system.
 
 

To build a brain we have to go from 0 to approximately 200 billion neurons in less than nine months (many neruons are lost as development progresses so a young adult ends up with approximately 100 billion).
 

The neurons in the brain are very well organized. Proper development requires the execution of three steps:

1) Creating neurons is called Proliferation
2) Placing neurons in the correct location is called Migration
3) Connecting neuronal axons & dendrites is called Differentiation
  Proliferation: New neurons are created by the division of stem cells. Stem cells continuously produce new neurons from the fifth week to the fifth month of gestation (Figure 18.2).
 

Migration: New cells are guided to their destination by radial glia. Radial glia stretch from the ventricle to the outside edge of the brain. New cells are deposited from the inside of the cortex (Layer VI) to the outside (Layer I) (Figure 18.4).
 

Differentiation: As soon as the cells are in the right location they begin to develop axons and dendrites. Each cell differentiates for a specialized function based on its location. This differentiation includes connecting axons and dendrites between neurons and targets (Figure 18.5).
 
 

Some axons travel great distances to make proper connections. Growth occurs at the end of the axon in a specialized structure called a growth cone (Figure 18.7). There are guidance systems to make sure axons get to the proper targets. There are three strategies growth cones use to find their targets.

1. The growth cone responds to molecular signals along the extracellular matrix (Figure 18.8). The extracellular matrix is a protein structure that traverses the space between neurons. The molecules on this matrix can do two things:
  a. Stimulate growth of the axon so it continues on to the target.

b. Repel the axon so it goes in a different direction.
 

 2. The growth cone responds to chemicals, called netrins, released by the target into the CSF.

3. The growth cone connects to other migrating axons using cell adhesion molecules (nCAM) (Figure 18.8). This allows a group of neurons to send axons to the same target area.
 

 The next step in development is keeping the neurons and synapses that are useful and eliminating the others. From infancy to adulthood this results in the loss of: 50% of the neurons in the brain (from 200 billion to 100 billion).
50% of the synapses in the brain (the visual cortex alone losses approximately 5000 synapses every second during adolescence) (Figure 18.11). In order to survive, neurons must do two things: 1. Have correlated activity with the target.
2. Take up chemicals called trophic factors (e.g., nerve growth factor).
  Despite the loss of neurons, brain weight increases from 350 to 1300 grams from birth to adulthood. That is because existing neurons grow and make connections (axons & dendrites). Producing more neurons and synapses than are necessary requires a tremendous amount of energy. Can you think of any advantages to this approach?
 

Sensory input has a huge influence on which neurons and connections remain in the brain. However, stimuli must occur during critical periods for development. Critical periods are the times when neurons need activity to strengthen their connections. For example, if you wear a mask so you can only see horizontal lines during the critical period for visual development, then you will only be able to see horizontal lines as an adult. The Neuroscientists Hubel and Weisel were awarded a Nobel Prize for this research.
 

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