Module : Development of the Nervous System

Lecture 6

Synapse formation & refinement

The neuron doctrine was proposed over a century ago.

Transition from a growth cone to a presynaptic membrane structure

Rapid adhesion takes place between the growth cone and its target. In this example this is between a neuron and the muscle.

Contact with the target also increases spontaneous and evoked transmission

Contact with target increases free calcium in the growth cones

In the muscles ACh receptors clustering is induced by the spinal nerves

It was discovered that neural agrin is important for receptor clustering

New AChR are added within hours of nerve innervation

Extrasynaptic receptors are actively prevented from being transcribed

Motor system

There is competition among multiple motor axons for a single target muscle fiber.

Input elimination reduces the axonal divergence. In the muscle this can observed by the fact that the total twitch tension that an individual axon exerts decreases over time.

Proper binocular fusion and stereoscopic vision depends on correct processing of information from both eyes.

Initially overlapping nasal axons from the opposite eye gradually segregate within the LGN resulting in the formation of layers of eye-specific domains. Blockade of retinal waves driven my amacrine cells prevents lamina formation. However patchy segregation still occurs due to additional mechanisms such as later glutamatergic waves.

Refinement of synaptic connections leads to a higher resolution visual map

Ocular dominance columns of neonatal monkeys at the level of IVc revealed by 3H proline injected into vitreous of one eye

HRP injections into one eye reveals the pattern of axon termination in the LGN of the cat about a week before birth

Post synaptic activity is important.

Imbalance of activity from the two eyes leads to ocular dominance columns and this occurs independent of visual stimulation in the beginning.

Binocular cells require synchronous activity from both eyes.

Critical period for ocular representation

It is still a long road even after the axons reach their final destination

The growth cone and its target have to transform into a synapse.

At the anatomical level and at the level of receptor organization several changes take place during the formation of the synapse. These changes are triggered by signals exchanged between the growth cone and the target.

A critical period exists for each modality of development

The refinement of synaptic connections is crucial for function. This phase of formation and withdrawal of connections depends on electrical activity. Molecular mechanisms underlying refinement during development may overlap with those involved in synaptic plasticity.