Lecture 18 - Circuit Construction II

Question 1

What is John Langley known for studying?

Answer 1

He’s known for studying the sympathetic pathways associated with the “fight or flight” response, like pupil dilation and blood vessel constriction. He studied through working with the superior cervical ganglion (anterior-most sympathetic ganglion).

Question 2

What happened when Langley stimulated the T1 and T4 preganglionic fibers?

Answer 2

Stimulation of T1 (thoracic level 1) preganglionic fibers coming from the spinal cord activate postganglionic neurons that cause pupil dilation in the eye. Simulation of T4 (thoracic level 4) preganglionic fibers activate postganglionic neurons that cause constriction of blood vessels of the ear.

Question 3

Axons from T1 and T4 run together in the same bundle to the ganglion. What does this indicate?

Answer 3

This indicates that there is an organization of connections in the ganglion that allows for specific behaviour effects.

Question 4

What did Langley find would happen when the cervical sympathetic trunk was cut?

Answer 4

He found that the injured sympathetic nervous system could regenerate following this cut. Behaviour responses would be lost upon cutting but could be re-established within a few weeks despite the ganglion having a mixed population of postganglionic targets.

Question 5

Despite the superior cervica ganglion having a mixed population of postganglionic cell targets, selective responses could be re-established within a few weeks after injury (cervical sympathetic trunk cut). What does this indicate?

Answer 5

This suggested that neurons make selective choices for their partners and connections.

Question 6

What layers of cells (in order) must light pass through in order to reach the photoreceptors in the retina?

Answer 6

Light must pass through ganglion cells, amacrine cells, bipolar cells, and horizontal cells.

Question 7

How do sidekick 1 and 2 proteins contribute to synaptic organization in the inner plexiform layer of the retina?

Answer 7

Cells on each side of the IPL (from ganglion cell layer and inner nuclear layer) meet up in different layers of the IPL depending on which proteins they are expressing. For example, sdk-1 expressing cells meet in layer S4.

Question 8

Suppose you take a SP+ INL cell and cause it to also express sdk-1. What type of GCL cell will it connect with, and in which IPL layer?

Answer 8

The cell will connect with a normal sdk-1+ cell in the S4 layer (normal layer for two sdk-1+ cells).

Question 9

Which 4 CAMs are involved in homophilic adhesion in the retina IPL?

Answer 9

Sidekick-1, Sidekick-2, DscamL, and Dscam

Question 10

What are basket cells?

Answer 10

Basket cells are inhibitory interneurons that form basket synapses near the axon initial segment of Purkinje neurons.

Question 11

What would happen in a mutant with ankyrinG knocked out?

Answer 11

The basket cells would not form inhibitory synpases at the AIS of Purkinje cells.

Question 12

Where is ankyrinG most concentrated?

Answer 12

AIS of Purkinje Cells

Question 13

What is used for synapse targeting of basket neuron axons to Purkinje neurons of the cerebellum?

Answer 13

Targeting is mediated by oligomeres of neurofascin with ankyrinG.

Question 14

What are the two options for an axon once it settles on a target?

Answer 14

It can form a synapse or retract/degenerate.

Question 15

What is a motor unit composed of?

Answer 15

A motor unit is composed of a motor neuron and the muscle fibers it innervates.

Question 16

What makes the neuromuscular junction a good system to study synapse formation?

Answer 16

It is a good system because it is large, relatively simple, and accessible. It also has good tools such as the electric organ of Torpedo californica, the original source for many NMJ-related proteins.

Question 17

True or False?:

The electric organ of Torpedo californica contains muscle-related electrolytes which are heavily innervated by motor terminals

Answer 17

True

Question 18

Where on the muscle fibre are AChRs found?

Answer 18

Synaptic Basal Lamina

Question 19

How many subunits are AChRs made up of?

Answer 19

5

Question 20

How many ACh molecules does each AChR bind?

Answer 20

2

Question 21

True or False?:

AChRs are ligand-gated potassium channels with some permeability to calcium.

Answer 21

False

AChRs are ligand-gated sodium channels with some permeability to calcium.

Question 22

What is often used to label AChRs (since it blocks ACh binding sites)?

Answer 22

The snake venom toxin alpha-bungarotoxin is used for labelling the AChRs.

Question 23

The muscle contains AChRs and VGSC (voltage-gated sodium channels) at the NMJ. In the below diagram of the NMJ, which channels are found in the red and which are found in the green?

Answer 23

Green - AChRs

Red - VGSC

Question 24

What happens during AChR organization during NMJ development?

Answer 24

AChRs are clustered early on, but undergo aggregation and reorganization during synaptogenesis and maturation.

Question 25

Cultured myotubes express AChRs that are distributed evenly across the cell surface. What happens if extracts from the synaptic basal lamina of Torpedo are placed on these myotubes? What does this mean?

Answer 25

The extracts induce AChR aggregation. This means something in the synaptic basal lamina causes aggregation. It was found that this aggregation was caused by agrin.

Question 26

What does local application of agrin on muscle fibres do?

Answer 26

It induces AChR aggregation without neuronal innervation.

Question 27

What secretes agrin?

Answer 27

Agrin is secreted from neurons and muscle (but in much lower concentrations from the muscle).

Question 28

What happens to muscles in agrin-deficient mutants?

Answer 28

They have small AChR clusters, decreased density of clusters, and less organized NMJs.

Question 29

What happens to the NMJ in agrin-/- knockout mice?

Answer 29

There are still clusters of AChRs, but they are much smaller. The axons will extend to the clusters and then extend along the muscle looking for more AChRs.

Question 30

How are NMJs formed during development?

Answer 30

The motor axon approaches a newly formed muscle cell. A nerve terminal is developed through the release of agrin. The muscle then forms a complex postsynaptic apparatus where AChRs are enriched at the surface.

Question 31

What are the two counter-balancing forces in AChR stabilization?

Answer 31

The scheer force of the action potential reaching the NMJ and ACh transmission creates a force that destabilizes AChRs. This force is counter-balanced by stabilization through agrin activity.

Question 32

True or False?:

ACh transmission destabilizes AChR clusters on muscle membrane. Agrin released from neuron stabilizes AChR clusters on muscle membrane.

Answer 32

True

Question 33

Why are AChR clusters large in mutant mice without motor neurons?

Answer 33

They are large because while there is no agrin, there is also no destabilizing force from ACh transmission.

Question 34

You are a doctor and see a 38 year old female patient come in with progressive fatigue and weakness. What disease may she have?

Answer 34

She may have myasthenia gravis.

Question 35

What happens in myasthenia gravis?

Answer 35

In it, your body develop antibodies against AChRs and musk, causing the NMJ to be much smaller and damaged. When there is a sequence of signals transmitted, the muscle gets fatigued because the antibodies have inhibited the NMJ.

Question 36

What is Lambert-Eaton syndrome?

Answer 36

It is a autoimmune disease that usually occurs with cancer. In it, antibodies are raised against presynaptic calcium channels. When multiple signals are transmitted, there is an action potential fatigue leading to inefficient/weak transmission. As such, the disease causes progressive fatigue and weakness.