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Questions and Answers
What do guidance signals primarily assist with in the embryonic body?
What do guidance signals primarily assist with in the embryonic body?
Which of the following is a characteristic of guidance signals?
Which of the following is a characteristic of guidance signals?
What is the mechanism through which growth cones interpret guidance signals?
What is the mechanism through which growth cones interpret guidance signals?
Which type of guidance signal is described as non-diffusible?
Which type of guidance signal is described as non-diffusible?
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What is meant by 'fasciculation' in the context of axon growth?
What is meant by 'fasciculation' in the context of axon growth?
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Which of the following signals is considered a long-range diffusible guidance signal?
Which of the following signals is considered a long-range diffusible guidance signal?
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What are the characteristics of attractive guidance signals?
What are the characteristics of attractive guidance signals?
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How do growth cones manage to navigate through a complex array of signals?
How do growth cones manage to navigate through a complex array of signals?
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What role do growth cones play in developing neurons?
What role do growth cones play in developing neurons?
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How do attractive and repulsive cues contribute to axon guidance?
How do attractive and repulsive cues contribute to axon guidance?
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What was the significance of Victor Hamburger's discovery regarding limb removal?
What was the significance of Victor Hamburger's discovery regarding limb removal?
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What determines the final pattern of synaptic contacts?
What determines the final pattern of synaptic contacts?
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Which molecules are involved in stabilizing formed synaptic connections?
Which molecules are involved in stabilizing formed synaptic connections?
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What initiates the cytoskeletal changes in the growth cone when a guidance signal is received?
What initiates the cytoskeletal changes in the growth cone when a guidance signal is received?
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Which principle describes the stabilization of inputs with correlated activity?
Which principle describes the stabilization of inputs with correlated activity?
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What is the primary function of microtubular cytoskeletal changes in a growth cone?
What is the primary function of microtubular cytoskeletal changes in a growth cone?
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Study Notes
Brain Development and Construction of Neural Circuits - Learning Objectives
- Students should be able to describe the processes of neurogenesis, differentiation, and cell migration.
- Students should be able to describe the process of target innervation.
- Students should be able to describe the principles of synapse formation and elimination.
Target Innervation
- How does a growing neural process navigate the embryonic body?
- Does the process know the entire route as it sets out?
- Growing processes use cues/signals to navigate.
- Processes also "piggyback" = fasciculation (along the pathway).
Classes of Guidance Signals
- Guidance signals guide growing processes in the embryo.
- Signals can be short-range or long-range.
- Signals can be attractive or repulsive.
- Signals are interpreted by the growth cone and the response is accordingly.
- Guidance signals act via concentration gradients.
- Some signals are non-diffusible (short-range), e.g., cadherins or ephrins, which derive from the extracellular matrix or are presented on target cells.
- Other signals are diffusible (long-range), e.g., netrin, semaphorins form concentration gradients.
How Guidance Signals are Sensed
- Growth cones (motile structures) are described by Cajal (1890).
- Growth cones are at the tip of growing axons and dendrites.
- Hand-like structures with receptors on the surface of the growth cone to sense guidance cues.
How We Know About Guidance Signals
- Identified through explant and cell culture experiments and genetic studies.
How Do Circuits Work Together?
- Long-range attraction
- Short-range attraction
- Short-range repulsion
Why Not All Neurons Cross?
- Long-range repulsion. Motor neurons - Slit + netrin-1
Axon Guidance Summary
- Developing neurons are guided to their targets by attractive and repulsive cues.
- Guidance signals act on the growth cone to determine the direction of growth.
- Upon receipt of a signal, the growth cone undergoes cytoskeletal changes that allow it to move forward or change direction.
- Once the direction is determined, cytoskeletal changes enable the laying-down of the axon in the desired direction.
- Targets are found and circuits are formed.
Synapse Formation
- Birth of neurons
- Outgrowth of axons and dendrites
- Synaptic connections are made.
- Refinement of synaptic connections.
- Target selection
- Address selection
Are All Contacts Worth Maintaining?
- Some synapses are kept, other are abandoned.
- Neurotrophins and electrical activity determine the final pattern of contacts.
- Hebb's rule, 1949: inputs that have correlated activity in time become stabilized.
Adhesion Molecules
- Presynaptic neurexins: organize the SV docking zone.
- Postsynaptic neuroligins: recruit PSD.
Developmental Cell Death
- Victor Hamburger discovered that limb removal results in reduced numbers of motor and sensory neurons in the chick spinal cord (1934).
- Surplus of motorneurons exist before limb development.
Once Circuits Are Formed, What Regulates Them?
- The target/cells release trophic factors.
- Learning and memory.
- Disease.
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