3: Wiring of the Brain: Axonal Guidance and Target Selection

Question 1

(OBJ) Describe the key facets underlying tangential migration of interneurons.

Answer 1

(sort of done elsewhere)

Question 2

(OBJ) Explain the relevance of disruption of specific classes of interneurons to diseases such as schizophrenia.

Answer 2

Bad migration = schizophrenia, other diseases

Question 3

(OBJ) Be able to summarize the key mechanisms by which pioneer axons and guidepost cells regulate axon outgrowth.

Answer 3

GUIDEPOST CELLS: serve as kiosks that direct outgrowing axons so they grow along an appropriate path; do this by altering signaling in growth cones

PIONEER NEURONS: specialized cells that are the first to grow

• -Many active filopodia
• -Followed with follower neurons
• -Can be transitory

Question 4

Differentiate trophic molecules from tropic molecules.

Answer 4

TROPHIC: support growth and survival

TROPIC: guide

Question 5

(OBJ) Describe the major specializations of growth cones (e.g., filopodia and lamellipodia) and how these structures change as axons traverse key choice points in their migratory routes.

Answer 5

GROWTH CONES: highly specific structures on developing neurons that detect specific environmental cutes to guide them to appropriate targets

• -Highly dynamic
• -Have lamellipodia (flat sheets) and filopodia (fingers) at tips to navigate
• -Differentiate into presynaptic terminal when final destination is reached

Question 6

(OBJ) Describe the general mechanisms that give rise to labeled pathways (e.g., the actions of ECM components and CAMs in axon guidance).

Answer 6

ECM involvement: ECM interacts with integrins in axons to allow axons to move

CAM and cadherins: expressed on pioneer and follower neurons, promote adherence among axon processes

Question 7

(OBJ) Describe the concept (not the specifics) by which temporal changes in tropic molecules and their receptors can first guide an axon to the midline in the developing nervous system and then later keep it from re-crossing.

Answer 7

Soluble chemoattractants and repellants:

• -Slit/Robo
• -Ephrins/Ephs
• -Netrin/DCC
• -Semaphorin/neuropilins
• -Neurotrophins/Trks

Work in concert with temporal expression

Question 8

(OBJ) Describe the concept of topographical maps within the brain and the reason that it is important to have this type of internal representation of our external world (e.g., provide a hypothesis as to why amputees might get phantom limb pain).

Answer 8

Gradients of EphrinA and Ephrin B = map

–Gives a uniqueness to every dimension, also allows some wiggle room