Week 2 - the dynamic synapse Flashcards
(31 cards)
Why do neurons have dendritic spines?
- To increase surface area and synaptic connection
- 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
Where to the majority of excitatory synapses occur?
At the dendritic spines
How do dendritic spines change shape
With f-Actin
How many proteins would you expect there to be in a synapse
Approximately 1500 different types of proteins
What is the physiological role of dendritic spines?
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
Does spinogenesis equal synaptogenesis
(yuste and bonhoeffer 2004)
No it doesn’t
Yuste and bonhoeffer showed that dendritic spines can appear when there is no pre-synaptic neurons in the area
synaptogenesis stages:
- there is an already established presynaptic axon and post-synaptic dendrite
- The dendrite sends out a thin and dynamic protusion called a filiopdia. This searches the area to find a suitable partner to connect with
- the previously dynamic filiopedia changes shape to become less long and less dynamic
- 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
- The adhesion molecule connects with a binding molecule on the pre-synaptic side, which starts to make the connection
- The NMDA molecules mean that the synapse already has the machinery they need for the synapse
- The synapse becomes more stable. This is driven particulary by certain types of adhesion protein.
What can imaging of fixed cells tell us about dendritic spines
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
What is the role of neuroligin 1 in synapses
how did barrow et al 2009 find this out
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
What is the relationship between N-cadherin and synapses
xie et al 2008t
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
How do dendritic spines change as the brain matures
They develop to become more short and stubby, then mushroom like, then multi-headed
How does the shape of dendritic spine impact its function?
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).
describe glutamate uncaging and how we can use it to learn more about dendritic spines
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
What has glutamate uncaging discovered about dendritic spines?
Glutamate uncaging induces spine formation. This is very similar to what you see in response to high frequency stimulation.
Glutamate uncaging can induce spinogenesis.
What did Kwon & Sabatini (2011) discover about spine-specific synaptic plasticity?
Kwon & Sabatini (2011, Nature) used 2-photon glutamate uncaging and imaging in hippocampal CA1 neurons to investigate synapse-specific plasticity.
They found that individual dendritic spines could undergo local, input-specific long-term potentiation (LTP) without affecting neighbouring spines.
This potentiation involved a local increase in AMPA receptor insertion and required NMDA receptor activation.
The changes were spatially restricted to the stimulated spine, showing no spread of plasticity to adjacent synapses.
Outline the structural plasticity of dendritic spines
Dendritic spines can change shape in response to different stimuli.
With LTP they get bigger. With LTD they get smaller
How does Kopec et al’s 2006 study show us that structural and functional plasticity are linked
Kopec et al. (2006) used two-photon glutamate uncaging on individual dendritic spines in hippocampal neurons to induce local synaptic potentiation.
They found that potentiated spines rapidly enlarged, and the size change was correlated with increased AMPA receptor-mediated currents, indicating functional strengthening.
They also observed that this spine growth and synaptic potentiation required NMDA receptor activation, linking it to LTP mechanisms.
Importantly, neighbouring spines did not show similar changes, confirming input specificity.
How is structural plasticity correlated with learning and memory?
yang et al 2009
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
Yang et al. (2009) conducted an in vivo study using two-photon microscopy to observe dendritic spine dynamics in the motor cortex of mice undergoing motor skill learning.
They found that learning a new motor task led to the rapid formation of new dendritic spines.
Importantly, a subset of these newly formed spines was stabilized over time.
The degree of spine formation and stabilization correlated with the performance improvement in the motor task, suggesting a link between structural changes and memory retention.
Conclusion:
This study provides direct evidence that learning induces specific structural changes in the brain—namely, the formation and stabilization of dendritic spines—which are associated with the encoding and retention of new memories.
Does dendritic spine structure link with synaptic function in vivo?
zhang et al 2015
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
How to image dendritic spines in vivo?
mCherry is a genetically encoded red fluorescent protein that can be expressed in neurons to label their morphology.
When targeted to the cytoplasm, it fills the entire neuron, including fine structures like dendritic spines.
Because mCherry is fluorescent and photostable, it allows researchers to perform live imaging using techniques like two-photon microscopy.
This enables the visualisation and tracking of dendritic spine dynamics (e.g. formation, elimination, or structural changes) over time in living animals.
Conclusion:
mCherry provides a bright, stable, and non-toxic marker for visualising dendritic spine structure in vivo, making it a powerful tool for studying structural plasticity during learning and memory.
how are structural and functional plasticity linked main conclusion
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
How does the dendritic spine size change occur mechanism
When calcium enters the neuron (typically through NMDA receptors during synaptic activity), it activates CaMKII (Ca²⁺/calmodulin-dependent protein kinase II).
CaMKII phosphorylates Kalirin-7, a Rho-GEF (guanine nucleotide exchange factor) that is critical for activating Rac1, a small GTPase.
Rac1 then triggers remodelling of the actin cytoskeleton, which is the structural framework that supports dendritic spines.
This cascade leads to spine enlargement, formation, or stabilisation, which are key processes in structural plasticity and long-term potentiation (LTP).
How does N-Cadherin stabilize synapses?
N-cadherin is a cell adhesion molecule located at synapses, where it forms homophilic bonds (binding to another N-cadherin molecule on the adjacent cell).
These bonds help to physically anchor pre- and post-synaptic membranes, stabilising the synaptic contact.
During synaptic activity, N-cadherin becomes more adhesive, reinforcing the connection at potentiated synapses.
It also interacts with cytoskeletal and signalling proteins, linking synaptic adhesion to structural plasticity and spine stability.
Disrupting N-cadherin function can lead to spine retraction and synapse weakening, showing its role in maintaining long-term synaptic changes.
How does dendritic spine structure relate to function?
Dendritic spines are tiny protrusions on dendrites where excitatory synapses form.
The size and shape of a spine influence its synaptic strength and plasticity:
Larger spines usually have more AMPA receptors and larger postsynaptic densities, correlating with stronger, more stable synapses.
Thin or filopodia-like spines are more dynamic and often represent immature or weaker synapses, capable of change during learning.
The spine neck regulates electrical and biochemical isolation, allowing individual spines to function as independent signalling compartments.
Structural changes (e.g. spine enlargement or stabilisation) are tightly linked to functional changes, such as LTP or memory formation.`
