LTP and hebbian plasticity 14/4 Flashcards
Define anterograde amnesia
Loss of ability to create new memories after a trauma
Define retrograde amnesia
Loss of memories or loss of access to memories formed before the trauma
What is Hebbian plasticity?
Simultaneous activation of two cells increases synaptic strength between the cells
Four criteria for Hebbian plasticity
1.) Input specificity. Only co-active pre and post synaptic activity undergo modification. 2. Cooperativity. Multiple inputs must be summated 3. Associativity. Weak inputs will undergo change if paired with strong inputs 4.) Longevity. The mechanism should last for a sufficient period of time
What were Hebbs three key concepts of memory?
- The Hebbian synapse: Cells that fire together wire together. 2. The cell assembly: Groupings of cells are connected through Hebbian plasticity to mediate perceptual binding 3. The phase sequence: Sequencing assemblies over time and space into complex percepts.
Why has the hippocampus been the primary site of study for hebbian plasticity?
1.) It’s the site of declarative memory 2.) Measurements and manipulations can be done through simple electrophysiology 3.) Highly discrete pathways with localised synapses 4.) Monolayer of excitatory cells as opposed to layers of cortex which contain bodies, dendrites, axons etc 5.) Relatively easy to keep alive in vitro
How can early LTP be differentiated from late LTP?
Early LTP does not require protein synthesis, whereas late LTP does. This can be shown by administering acinomyocin (protein synthesis inhibitor) during tetanic (high frequency) stimulations, which blocks late LTP but not early
formation and storage of memories which last a lifetime is underpinned by LTP, requiring protein synthesis and long term synaptic modification. What is the leading hypothesis for the mechanism which locates newly synthesised proteins to the correct synapses?
‘The synaptic tag hypothesis’ states that there is a chemo-attractant or long lasting message at the recently stimulated synapse that causes newly synthesised proteins to migrate there.
This would explain associativity between weakly stimulated synapses and strongly stimulated synapses.
This theory is in opposition with others which state that there is some kind of ‘address’ on the proteins for them to be sent to the synpase.
Other theories show that proteins are synthesised by local ribosomes at the synapse which is supported by some evidence.
What are the three stages of LTP?
Induction
Expression
Maintainence
Which molecular events underpin induction of LTP?
Activation of NMDA receptor [voltage dependent calcium channel].
For this to occur, Mg2+ must be removed through cell depolarisation e.g. through glutamateric activation of AMPA receptors.
NMDA antagonists block LTP induction by tetanic stimulation of the hippocampus. They also block learning of the morris water maze
Which molecular events underlie the expression phase of LTP i.e what events occur to change synpatic strength?
AMPA receptor insertion
- If AMPA receptor insertion is blocked then LTP does not occur.
How is LTP maintained?
- PKMzeta - a type of memorase?
- PKMzeta is a specialized type of PKC which is constituively transcribed.
- It is involved in AMPAR insertion during LTP
- Increasing intracellular Ca2+ stimulates enzymes such as CaMKII which releases the translational block on PKMzeta.
- PKMzeta also inhibits its own translational block - positive feedback system which results in PKMzeta only being translated in places where it already present.
How is the NMDA receptor hebbian?
Due to its constitutive magnesium block, it requires co-commitant pre and post syanptic activity in order to be activated. The post-synaptic cell must already been in a state of depolaristion (via previous activation of AMPA receptors) when another AP arrives in the pre-synaptic cell, releasing glutamate. This will allow Mg2+ block to be removed as post-synaptic cell becomes even more depolarised.
