Week 2 - Synaptic Plasticity Flashcards
What is Explicit/Declarative memory?
Memory of facts/events also spatial memory
Consciously recalled
Easy to acquire, easy to forget
What is Implicit/non-declarative memory?
Memory for skills,habits and behaviours
Without conscious awareness once learned
Requires repetition and practice
Less likely to be forgotten once learned
What underlies the formation of short term memory?
Buffers
Where is Hippocampus found?
In the temporal lobe
What does hippocampus relate to?
The rest of the limbic system
What does the hippocampus connect to?
Hypothalamus
Mammillary bodies
Fornix
Amygdala
What does Amygdala mediate?
Fear conditioning
What is the stratium involved in?
Motor skill learning
Learning of skills
What happens when the hippocampus is removed?
The ability to remember and the ability to acquire new information/history
What does the limbic system consist of?
Cingulate gyrus
Parahippocampal gyrus
Amygdala
Hippocampus
What 2 areas does the hippocampus Contain?
Dentate gyrus
Hippocampus proper
What is the trisynaptic loop?
relay of synaptic transmission in the hippocampus
What are the 3 major cell groups of the trisynaptic loop?
Granule cells
CA3 (Cornu Ammonis area 3) pyramidal neurons
CA1 (Cornu Amnonis area 1) pyramidal cells
Where does the first projection of the hippocampus gyrus occur between?
Entorhinal cortex
Dentate gyrus
Where does the entorhinal cortex transmit its signal from and to?
From: parahippocampal gyrus
To: dentate gyrus
Via granule cell fibre (performant path)
Where does the dentate gyrus synapse on?
Pyramidal cells in CA3 via mossy cells fibres
Where does CA3 fire to?
CA1 via Schaffer collaterals which synapse on the subiculum and are carried out through fornix
What is hippocampus associated with?
Long-term memory
What can damage to hippocampus lead to?
Loss of memory
Difficulty in establishing new memories
New information is not stored, but I do information remains intact
What does hippocampus play a major role in?
Encoding and storing information
Who won the Brain prize in 2016?
Timothy Bliss
Graham Collingridge
Richard Morris
What did Timothy Bliss do?
Discovered LTP
Record imperforate pathway (entorhinal cortex to granule cells connections)
In one hemisphere, record a stable recording over many hours
In another hemisphere apply a higher frequency activity (stimulate axons)
Record responses
What happens after an increased frequency activity is applied?
The response size will also increase
What did Graham Collingridge do?
Molecular mechanism behind LTP
Led to discovery of NMDA receptor
What happens when NMDA receptor is working properly?
Important for learning and memory
What happens when NMDA receptor is not functioning?
Major neurological and psychiatric conditions
What did Richard Morris do?
Proved the importance of LTP to animals ability to learn and remember
Treated rats with a special drug that blocked the normal LTP process
Without LTP what were animals incapable of doing?
Learning and navigating their way round a maze
What was Hebb’s postulate?
Neurons that fire together wire together
Where does an increase in synaptic efficacy arise from?
Presynaptic cells repeated and persistent stimulation of the postsynaptic cell
Where did Bliss and Lomo record from?
Dentate gyrus of anaesthesised rabbits in vivo
Performant path input to dentate gyrus (granule cells)
What produced a stable synaptic response?
Stimulation of axons at low Basal rate
What resulted in a persistent increase in response size - LTP?
Application of a single high frequency stimulus
How do you induce LTP?
Apply 100Hz of tetanus for 1 second
How to achieve 4-5 action potential?
Small bursts of 4 pulses over 200ms
What is feta frequency?
Frequency used for the brain to learn
What are the basic properties of CA3-CA1 LTP?
Input specificity
Associativity
Cooperatively
Longevity
What is Input specificity?
Once induced, LTP at one synapse does not spread to other synapses
What is associativity?
One stimulus is weaker and the other stronger, the two types of stimulation will associate
What is cooperativity?
LTP can be induced by either strong tetanic stimulation of a single pathway
Or cooperatively via weaker stimulation of many
Activate a single pathway above a certain threshold
What is longevity?
In living animal, LTP can be recorded up to 360 days after induction
Maintain strength for a very long time
Encore long lasting memory
What does dentate granule cells receive?
Perforant path from EC
What can stop AP conduction?
Na+ deactivation
What happens at higher frequencies?
Activate more synapses
What are the other properties of CA3-CA1 LTP?
Reversibility
Saturation
What is reversibility?
LTP effects can be reversed/turned back
What are responses in associativity mediated by?
AMPA receptors
What happens through the Glutamate subtype AMPA receptors?
Fast neurotransmission of the brain
What is GluN1 binding site bind to?
Glycine NT
What does GluN2 bind to?
Glutamate
What does binding of both glycine and glutamate result in?
Channel to open
How do you activate NMDA receptor?
changing AMPA response
How can you stop the induction of LTP?
Apply Gamma DGG and give tetanus
What is the role of gamma DGG?
Blocks both NMDA receptors
Blocks a little bit of the AMPA receptors
How are NMDA blocked?
By magnesium during resting membrane potential
How does depolarisation occur?
Activation of AMPA receptors
What are co-transmitters for NMDA receptors?
Glycine and glutamate
What happens under base line conditions?
Release of Glutamate (activates AMPA receptors)
Product EPSP in the cell
What are the channels that the inhibitory crops activate?
Ionotropic GABA A receptors
Glutamate receptors
AMPA/NMDA type
What are GABA B receptors?
Pre-synaptic alpha receptors
Lint the release of GABA
Cause a decrease in chloride current
What does the activation of inhibitory network affect?
Excitatory network
What are excitatory cells surrounded by?
Cloud of inhibitory cells
What occurs during Basal low frequency transmission?
IPSP stops NMDA receptor activation
What occurs during repetitive stimulation of GABA B receptor?
Activation presynaptically reduces GABA release which reduces postsynaptic IPSP
Where is Ca2+ coming from?
Extra synaptic into the intrasynaptic site binding to the flourescent dye and give us the signal inside
What are involved in LTP in adults?
Multiple kinases
What does the kinases have the ability to do?
Change how the cell functions
Phosphorylate receptors and phosphorylate different factors inside of the cell
What can kinases do?
Block LTP
Short term potentiation
30 minutes or so
Early LTP
A few hours
Protein synthesis independent
Late LTP
Protein synthesis dependent
What is the time constant of decay of STP?
10-20 minutes
What is the time constant of decay of PTP?
6 seconds
Which one is a NMDA receptor dependent?
STP
Which one is the NMDA receptor independent?
PTP
What can block induction of STP?
Activation of AP5
What does compound UBP145 do?
Block GluN2d subunit of NMDA receptor
Why do we need STP?
We need to remember short lasting memories
How is transmission increased?
Presynaptic changes and increase amount of Glutamate
Increase release probability - more synapses will release more reliably when an AP comes
Change the number of AMPA receptors
Externalise more receptors and increase the response
Change the amount of current the receptor can pass through
Phosphorylate AMPA receptors - make opening larger leading to more influx of Na+
Grow more synapses and make more connections
What is pre-pulse facilitation?
When two pulses are given at short intervals
What are the variety of mechanisms of ways of STP and LTP expression depend on?
Developmental stage
Brain region
Induction parameters
What is the summary of CA3-CA1 LTP?
Induction is NMDA receptor-dependent
Requires postsynaptic calcium rise
Involves multiple kinases
May involve changes in postsynaptic AMPA receptor number or conductance
Involve presynaptic increase in Glutamate release
Involve multiple processes
What is Mossy fibre LTP?
Happens at CA3 cells
Different from CA1 LTP
A lot of kainite receptors
Kainite receptors are ca2+ conducting
What is CA3 to CA1 synapse?
glutamatergic
What is Mossy fibre LTP?
NMDAR independent
Does AP5 block LTP in Mossy fibres?
No
What is Mossy fibre LTP blocked by?
Antagonists of KainateRs
What is an example of an antagonist against kainate receptors?
Acet
When is LTD induced?
Low frequency stimulation is given to the axon
What is depression of synaptic transmission sensitive to?
AP5
What happens when you use electrode to block ca2+?
Block the ability to induce LTD
How else is LTD induced?
with a receptor that has GLUN2B subunit
How is LTD seen?
Slices prepared from young rats
What is LTD dependent on?
Activation of protein phosphatases
What can LTD be?
Saturated and reversed
What is an example of LTD mechanism that exists in adults?
mGluR LTD
What are kinases in LTP insensitive to?
Ca2+
What are phosphatases more sensitive to?
Ca2+
What are LTP and LTD?
Complementary types of plasticity
What does induction of LTP produce?
Large intracellular calcium rise for a short period of time
What does induction of LTD produce?
Smaller rise in calcium over a longer time scale
What are kinases involved in?
LTP (e.g. CaMKII)
Insensitive to calcium
Need a big calcium change to be activated
What are phosphatases involved in?
LTD
More sensitive to calcium
Activated by small calcium changes
