Week 2 - the dynamic synapse

Question 1

Why do neurons have dendritic spines?

Answer 1

1. To increase surface area and synaptic connection
2. To be able to compartmentalise electrical and biochemical signals from the cell. A single cell recieves thousands of inputs. At the level of the dendritic spine, not all the information is passed on. Instead a certain threshold of information must be reached before it is passed on away from the dendrite

Question 2

Where to the majority of excitatory synapses occur?

Answer 2

At the dendritic spines

Question 3

How do dendritic spines change shape

Answer 3

With f-Actin

Question 4

How many proteins would you expect there to be in a synapse

Answer 4

Approximately 1500 different types of proteins

Question 5

What is the physiological role of dendritic spines?

Answer 5

synapse formation - dendritic spines appear in the dendrites to search out the pre-synaptic neuron to connect with

structural encoding of information - when synaptic activity is induced, existing dendritic spines get bigger

Question 6

Does spinogenesis equal synaptogenesis

(yuste and bonhoeffer 2004)

Answer 6

No it doesn’t

Yuste and bonhoeffer showed that dendritic spines can appear when there is no pre-synaptic neurons in the area

Question 7

synaptogenesis stages:

Answer 7

1. there is an already established presynaptic axon and post-synaptic dendrite
2. The dendrite sends out a thin and dynamic protusion called a filiopdia. This searches the area to find a suitable partner to connect with
3. the previously dynamic filiopedia changes shape to become less long and less dynamic
4. Certain proteins are recruited to the protrusion that allow it to make a physical connection to the pre-synaptic side. This involves NMDA receptor complexes, PSD-95 and a neuroligand adhesion molecule. These molecules are thought to be diffusing along the dendrite until they come across the protusion
5. The adhesion molecule connects with a binding molecule on the pre-synaptic side, which starts to make the connection
6. The NMDA molecules mean that the synapse already has the machinery they need for the synapse
7. The synapse becomes more stable. This is driven particulary by certain types of adhesion protein.

Question 8

What can imaging of fixed cells tell us about dendritic spines

Answer 8

You can look at the morphology and localisation of proteins

You can look at how the shape of the spine changes according to treatment or genetic manipulation

Question 9

What is the role of neuroligin 1 in synapses

how did barrow et al 2009 find this out

Answer 9

Neuroligin 1 recruits psd-95 to synapses

They tried to create a synapse by clustering diffuse molecules of neuroligin 1 together using a clustering complex

they found that when neuroligin 1 was clustered, psd-95 increased massively and accumulated in the clusters

This shows that neuroligin 1 clustering is sufficient to recruit psd-95 to synapses and anything else that psd-95 is attached to. We know that psd-95 is attached to NMDA receptors, so this starts the formation of a functional synapse

Question 10

What is the relationship between N-cadherin and synapses

xie et al 2008t

Answer 10

N-cadherin stablisizes synapses

N-cadherin is an adhesion protein.

Xie et al, 2008 found that as dendritic spines get bigger, there is more N-cadherin density

So they manipulated the density of N-cadherin

they found that when N-cadherin was clustered, big thick dendritic spines appeared. When n-cadherin was interefered with, thin and long filapodeian like protusions appeared.

This shows that n-cadherin is involved in the stabalization of filapodeia shape

Question 11

How do dendritic spines change as the brain matures

Answer 11

They develop to become more short and stubby, then mushroom like, then multi-headed

Question 12

How does the shape of dendritic spine impact its function?

Answer 12

Larger dendritic spines have more AMPA receptors (xie et al, 2007)

Functional AMPAR content is correlated with spine size - big dendritic spines lead to bigger electric potentials (matsuzki et al, 2001).

Question 13

describe glutamate uncaging and how we can use it to learn more about dendritic spines

Answer 13

If you take a slice of the hippocampus and growing it in a dish, maintain and grow it.

If you cage glutamate, you make it inert

You can then uncage it by shining it with a laser

You can combine this with two photon microscopy and then you can uncage glutamate at the level of 3 microns which is equivalent to the level of one single dendritic spine

Question 14

What has glutamate uncaging discovered about dendritic spines?

Answer 14

Glutamate uncaging induces spine formation. This is very similar to what you see in response to high frequency stimulation.

Glutamate uncaging can induce spinogenesis.

Question 15

Outline the structural plasticity of dendritic spines

Answer 15

Dendritic spines can change shape in response to different stimuli.

With LTP they get bigger. With LTD they get smaller

Question 16

How does Kopec et al’s 2006 study show us that structural and functional plasticity are linked

Answer 16

The induction of chemical ltp caused the spines to increase in size and the amount of Glu ampa receptors also increased

As spine size increased, the amount of ampa receptors also increased

Question 17

How is structural plasticity correlated with learning and memory?

yang et al 2009

Answer 17

Gave a living mouse a craniotomy

Imaged neurons in the motor cortex before they placed them in a rotarod

imaged neurons again after they learnt the rotarod

Found that post training, there were more dendritic spines on the neurons and some of the pre-existing dendritic spines have gotten bigger

Question 18

Does dendritic spine structure link with synaptic function in vivo?

zhang et al 2015

Answer 18

Zhang et al -

as they stimulated the whiskers of mice, they could see that the dendritic spines got bigger and bigger over time

also, as the dendritic spines get bigger, the intensity of AMPA subunits increases

do more research/check this paper

Question 19

how are structural and functional plasticity linked main conclusion

Answer 19

The more synaptic activity, the bigger the dendritic spines, the more spines there are and the more AMPA receptors of the dendritic spines, leading to changes in synaptic strength

Question 20

How does the dendritic spine size change occur mechanism

Answer 20

When you get a calcium influx into the cell

Camp kinase 2 phosphorlyates kalarin 7

this is required for rac1 activity

Rac1 protein activates the actin cytoskeleton

This leads to changes in dendritic spine structure