Postsynaptic receptors and synaptic plasticity Flashcards
Where is the post synaptic density (PSD) located?
On a spin neck, at the tip of the spine head
Describe the post synaptic density (PSD)
- An electron dense thickening of postsynaptic membrane of synapses, the PSD contains a high concentration of structural and signalling proteins connected physically and functionally to postsynaptic NT receptors and transsynaptic adhesion molecules.
* - PSD found at the tip of dendritic spines
- PSD is directly apposed to the presynaptic active zone—which is the site of the release of NT
- The space underneath the PSD is occupied by actin filaments, the major cytoskeletal component of dendritic spines
- neighbouring the PSD are endocytic zones which are hot spots for endocytosis of NT release.
An electron dense thickening of postsynaptic membrane of synapses, the PSD contains a ______________________ of structural and signalling proteins connected physically and functionally to postsynaptic NT receptors and transsynaptic adhesion molecules.
High concentration
An electron dense thickening of postsynaptic membrane of synapses, the PSD contains a high concentration of _______________________ and _______________________ connected physically and functionally to postsynaptic NT receptors and transsynaptic adhesion molecules.
Structural and signalling proteins
An electron dense thickening of postsynaptic membrane of synapses, the PSD contains a high concentration of structural and signalling proteins connected physically and functionally to______________________________ and ____________________________.
Postsynaptic NT receptors and transsynaptic adhesion molecules.
At the PSD we see elements like ______________ or __________
F-actin or filaments
What is found at the PSD
Post synaptic receptors, structural proteins, and various signalling proteins which can be linked functionally.
What is the general structure of the PSD
Endocytic zone is adjacent to the active zone, recycling of receptors occurs through endosomal structures, cytoskeleton, various signalling and structural proteins are present.
There are a lot of diff __________ found on the PSD that are important for synaptic transmission, synapse formation and development.
Proteins
All the receptors present at the PSD are ____________ and are directly opposite of the ____________________
Clustered, presynaptic active zones
What are the two types of receptors at the PSD
Receptors on the PSD can be classified as ligand gated ion channels (ionotropic receptors) and G-protein coupled (metabatropic) receptors
Describe how ligand gated ion channels (inotropic receptors) work
- NT comes in an binds to receptors
- Receptor opens and allows ions to flow through the opening
Describe how G-protein coupled (metabatropic receptors) work
- NT comes and binds to receptors
- this activates a G-protein subunit
- different G- proteins subunits affect various intercellular messengers or they can modulate ion channels directly leading to ion channels opening and ions coming in through the postsynaptic neuron.
Describe type of receptors when looking at a glutamatergic neuron and a GABAergic neuron
- Glutamatergic is excititory neurotranmitter and GABA is inhibitory neurotransmitter
- On the post syanptic neuron it has both ionotropic and metabatrobic receptors
- there is also glial cell that has a few metabatropic receptors on it; bc in some cases glia are able to detect neurotransmitter release, and can modulate it
- When glutatmatergic presyantic neuron releases glutamte it can now bing to ionotropic glutatmtergic receptors like NMDA, AMPA or Kianate
- Can also bind to metabatrobic glutamate receptors
- Leads to excitation of the post synaptic neruon
- GABAergic release GABA that can bind to ionotropic GABAergic receptors;can cause inhibition
- The two presyanptic neurons also have their own metabatropic recptors allowing them to have a feedback loop where they can detect NT release and this can modulate how much NT they are releasing
- There is a fair bit of communication between neurons
What are the diff types of glutamate receptors
- Ion channel (inotropic) receptors include: NMDA, AMPA and Kainate. All these lead to fast excitatory response.
- G-protein (Metabatropic) receptors include: Group I, Group II and Group III. Group I leads to slow excitatory response while group II and group III lead to slow inhibitory response.
When glutamate binds to ionotropic receptors
- in the case of AMPA kainate receptors: let Na in
- In the case of NMDA receptors: allow both Na and Ca in
AMPA receptors
- AMPA receptors are responsible for the bulk of fast excitatory synaptic transmission throughout the CNS and their modulation is the ultimate mechanism that underlies much of the plasticity of the excitatory transmission that is expression in the brain.
- Increasing the postsynaptic response to a stimulus is achieved either through increasing the number of AMPA receptors at the postsynaptic surface or by increasing the single channel conductance of the receptors expressed.
NMDA receptors
- At resting membrane potentials NMDA receptors are inactive. This is due to a voltage dependent block of the channel pore by Mg ions, preventing ions to flow through
- sustained activation of AMPA receptors depolarizes the postsynaptic cell releasing the channel inhibition and thus allowing NMDA receptor activation.
- Unlike GluA2-containing AMPA receptors, NMDA receptors are permeable to Ca ions as well as being permeable to other ions. Thus NMDA receptors activation leads to a Ca influx into the postsynaptic cells, a signal that is instrumental in the activation of a number of signalling cascades.
Kainate receptors
• Kainate receptors have classically been implicated in eplieptogenesis
G-protein coupled receptors
• Various G proteins can activate various signaling pathways
What are the two types of GABA receptors
GABAa- ligand gated ion channels (ionotropic receptors)
Describe GABAa receptors
• Structure of GABAa (these are ionotropic)
How does activation of GABAa receptors produce depolarization in immature but not adult neurons
• GABA is inhibitory
GABAa receptor endocytosis
• Adjacent to the postsynaptic density are endocytic zones; we can have receptors recycling here
Dysregualtion of GABAa receptors and epilepsy
What can go wring when we have disregulation of GABAa receptors recycling
Describe presynaptic GABAb receptors
• Can have these metabatropic GABAb receptors both pre and post syanaptically
Describe postsynaptic GABAb receptors
• Also found postsynaptically
Synaptic plasticity
• The two major forms of long lasting synaptic plasticity in the mammalian brain are LTP and LTD— which are characterized by a long lasting increase or decrease in synaptic strength respectively.
Long term potentiation LTP
LTP is a long last increase in the synaptic response of neurons to stimulation of their afferents following a brief high frequency stimulus. LTP lasts for hours or days
Long term depression LTD
LTD is long lasting decreases in the synaptic response of neurons to the stimulation of their afferents following long low frequency stimulation.
Molecular mechanisms of LTP and LTD
• Pre synaptic terminal releases glutamate
LTP mechanism
• The induction of LTP triggered by activation of NMDA receptors. This ionotropic receptor are inactive. This is due to a voltage-dependent block of the channel pore by magnesium ions, preventing ion flows through it.
LTD mechanism
• The induction of LTD is triggered by activation of NMDA receptors.
Structural and functional changes at glutamatergic synapses during LTP
• When we induce LTP we see structural changes and we see changes in the size of spine head and dendrites.
glutamate excitotoxicity
• Too much NT released and we get overstimulation
