The dynamic synapse 25/4 Flashcards
What is the post synaptic density?
A protein dense specialization attached to the postsynaptic membrane. There is a high concentration of neurotransmitter receptors, PSD-95 proteins and adherins
What are the key post synaptic density proteins?
- PSD-95
- NMDA
- Neurexin/neuroglin pre/post synaptic adhesion proteins which bind to each other
- N-cadherins (neuronal) - adhesion proteins which bind to themselves very strongly
What is the function of dendritic spines?
- Synapse formation
- Encoding of information at the structural level (experience depedent pruning, increase in size or number of dendritic spine)
Spinogenesis
The generation of a dendritic spine
Difference between synaptogenesis and spinogenesis
Formation of a dendritic spine is not necessarily the formation of a synapse and synapses can form with pre-exististing dendritic spines, however synaptogenesis and spinogensesis may often be concurrent events
What are the three models of synaptogenesis?
Sotelo model: An axon grows towards a pre formed dendritic spine to form a synapse. occurs immediately before and after birth where there is very little formation of dendritic or axon arbours.
Millers/peters model: There is already a proximal relationship between the axon and the dendrite, but no synapse has been formed until there is a signal (i.e. concomitant activation). Found primarily in early development.
Filopodial model: The dendritic spine begins to form and establish a protrusion (not yet containing proteins necessary to become a dendritic spine and then synapse). Once it reaches the target axon, it’s proteome begins to change as it forms a synapse. This is an adulthood model of synaptogenesis.
What are the key steps in synapse formation?
- Target selection.
- Synapse formation/spinogenesis
- Initial synaptic connectivity. Post synaptic side is recruiting important proteins – PSD-95, NMDA receptors and adhesion molecules. If adhesion and detection of glutmate does not occur then the process degrades.
- Recruitment of additional proteins. Adherins will provide stronger connections. Spine head becomes larger
- Stabilisation of the conneciton.
What are the three main morphologies of spines ?
- *- Large, stable.** The surface area of their presyanptic connections is greater.
- Long, thin, unstable. These are highly transient spines that can appear and disappear from one day to the next.
- Newly formed.
How do spine morphologies relate to their function?
Larger stable spines have a higher expression of AMPA GluN1. Delivering experimental puffs of glutmate above each synapse results in much greater depolarisations within larger syanpses. They are therefore set up for a greater functional connectivity.
What is the relationship between spine number and development?
Formation. Before birth and throughout childhood there is a rapid increase in the number of
Elimination. During adolescence, there is a refinement and pruning back of spines.
Maintainence. Throughout adulthood there is a very gradual decline in the number of spines.
What is dynamic about spines?
They are not only changing over time, but over night. Processes of spine formation, englargment, shrinkage and elongation can be visualised in living animals whilst they are sleeping occuring at the time frame of minutes.
This is likely due to a combination of external factors (glutamate signalling) and instrinsic dynamic activity.
What may be driving the dynamics of spine morphology?
F-actin is a cytoskeletal protein found within spines. Actin being transformed from G-actin to F-actin underlies the remodelling of synpases, supported by many other proteins.
If cells are treated with F-actin toxins, then spines become much smaller, thinner and disappear. Regulation of F-actin is critical for the maintainence of spines.
How do dendritic spines underly the structural encoding of information?
Increased input to a neuron (i.e., under learning conditions) results in an increase of spines, and over time produces a strengthing of pre/post synaptic connections. Decreased input results in a decrease in spines and connections.
This is a structural plasticity which may underly encoding of infomation.
PSD-95
postsynaptic density protein 95.
It is a scaffolding protein which allows for the clustering of receptors, ion channels, and signaling proteins. It is important in synaptic plasticity and LTP.
