Week 2 Topic 1

Question 1

Talk about a study that presents evidence that astrocytes might affect behavior!

Answer 1

Han and colleagues performed a study in 2013. In an intriguing set of experiments, they transplanted human glial progenitor cells in immunosuppressed mice. These progenitors survived, they migrated long distances and that gave rise to astrocytes with typical features of human ones.

Surprisingly, when Han and his colleagues examined the behaviour of these mice, they found mice with human astrocytes perform better in learning tasks and displayed and improved long-term potentiation, which is a strengthening of synaptic connection, which is thought to be the mechanism underlying learning and memory. Four astrocytes may be responsible for human cognitive abilities.

Question 2

How can astrocytes affect behavior?

Answer 2

Through their homeostatic role

Through their ability to release neurotransmitters

(glial transmission)

Through their ability to form networks

Question 3

What is a tripartite synapse?

Answer 3

It is a synapse composed of three elements. Two neuronal, the pre- and postsynaptic terminal belonging to two separate neurons and an astrocytic process.

Question 4

How does the tripartite synapse work? How does glial transmission work?

Answer 4

During synaptic activity, neurons release neurotransmitters. An astrocyte responds to these neurotransmitters.

We have elevations of calcium, and in turn, they control neuronal excitability in synaptic transmission through calcium-dependent release of glial transmitters.

The glial transmitter that astrocytes can release are glutamate, GABA, ATP, adenosine, D-serine, et cetera. Probably every single transmitters that neurons can also release, and probably also express receptor transporter for all the major neurotransmitters.

Question 5

How do astrocytes regulate sleep?

Answer 5

For some time it has been known that adenosine plays a role in controlling sleep homeostasis. Accumulation of adenosine during wakefulness promotes sleep. On the contrary, adenosine antagonist, such as caffeine, notoriously promote wakefulness.

A number of studies have shown that the source of adenosine is astrocytes, and these regulate sleep homeostasis. Astrocytes actually release ATP, and this is converted to adenosine extracellular. Astrocytes can release gliotransmitter by different pathways, including exocytosis.

Question 6

What can astrocytic networks do?

Answer 6

1. Evidence is available that they can regulate the generation of a rhythmic firing pattern in neurons. This is necessary for several vital functions, such as respiration and mastication. (F.e. Respiratory rhythm is disrupted in Rhett Syndrome, which is an autism spectrum disorder that is a neurodevelopmental disorder.)
2. Active astroglial networks have been also proposed to function as a master hub, which integrates the result of distributed processing from several brain areas and supports conscious states. Indeed, Pereira and Furlan in 2010, proposed that astrocytic networks are essential for voluntary behavior. Only automatic behavior could be executed purely by neuronal networks.

Question 7

What could be the consequence of astrocytic dysfunction?

Answer 7

Dysfunction of these astrocytic networks, therefore, could lead to cognitive impairment. It is however, not clear if changes to the astrocytic network are cause or consequence of neuronal dysfunction.