LTP induction Flashcards
Bliss and Lomo (1973)
If you give short burst of neural activity in the dentate gyrus in rabbit hippocampus – then you can have LTP – long lasting augmentation in the communication between two cells in the hippocampus
Short bursts of activity caused long lasting change – this is the first time that this was shown in the experimental setting for the first time
It lasted for a quite a few hours - how long does it last?
Programme of work had started in 1966
Bliss and Medwin (1973)
Showed that the time scale for the effects of LTP in – was 16 weeks in the hippocampus of an anaesthetised rabbit - this was as long as they were able to sustain the recording
a group in New Zealand then improved this
Hebb’s postulate (1949)
published many years before the Bliss and Lomo findings and published in a book called The Organisation of Behavior
When an axon of cell A is near enough to excite cell B and repeatedly
or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.
This is what he thought was the neural basis of neuronal synaptic plasticity
LTP shares quite a number of the qualities which Hebb postulates that the synapses have for synaptic plasticity to happen
Malenka et al 1989
Hebbs postulate is tested and shown to be correct in the context of LTP
They stimulate the presynaptic cells, depolarise the postsynaptic cell - giving partnered stimuli - depol in the post synaptic and AP in the presynaptic cell. When the pairing is desynchronised (stimulate and stop stimulating at the same time as depolarising the post synaptic cell, and then stimulating it again once the depol is finished), the EPSP does not change in amplitude.
However, if the stimulus continues, during the period of postsynaptic depolarisation, you see very robust clear potentiation of rwsponse.
Pre and post synaptic activity which is synchronisedgives rise to LTP. (similar to Hebb’s postulate)
Three textbook characteristics of LTP
specificity, associativity, cooperativity
what is the main characteristic of synaptic plasticity? why have the others come about?
The main characteristic is the input specificity. The others arise form early research
Input specificity - Andersen et al 1979
Imagine a cell (cell 1) has 4 synaptic inputs, but on training on the Hebbian form of plasticity, the depolarisation in cell 1 partnered with the transmitter release from cell A can produce a change at one node and one node only. This is input specificity. The other synaptic inputs do not change their activity or status. Only the synapse that is causing the association between depot and transmitter release is increasing.
Cooperativity - McNaughton et al 1978
One synaptic input is too modest in the magnitude of the generated EPSP, to sufficiently give rise to adequate depolarisation in the post synaptic cell because the response is not the 1mV but around 100 microvolts, which wont generate a large depolarisation in the postsynaptic cell. So if you have lots of synaptic inputs to cooperate, then you could produce taken together an adequate input to get the required response to have the Hebbian like pairing.
You can still have input specificity, but cooperation between two adjacent synaptic inputs could cause a big enough response in the post synaptic cell to give rise to give potentiation at the two nodes. although some of the degrees of freedom is lost, this at the time was the only way that people could prove that the plasticity happened.
What we now know is that these cells are quite capable to support APs in their dendrites and cause back-propagating action potentials. This gives a robust production of depolarisation without the need for other inputs.
Cooperativity was came out of the fact that the scientific community was unaware of the back propagating action potentials.
Associativity - Brown et al 1983
Brown was interested in seeing if LTP could be used to generate associative plasticity. in the style of Pavlov’s dog, but at the level of the synapse.
This is about providing weak and strong synaptic stimuli, partnering them and seeing if that generates LTP. This is very possible.
But this is falling out of textbooks?
Collingridge et al 1983
LTP is dependent upon activation of the NMDA receptor
APV - a drug which is an NMDA antagonist. If you apply this drug to an excitatory synapse, nothing happens, no change in the performance of the synapse. This experiment was repeated by many others to reach the same result.
A wide variety of other glutamate receptor antagonists were also used to apply to the brain tissue to have no effect.
Even though these receptors are present in abundance at the site of interest, but they seem to be having no action in the synaptic transmission??
Collingridge and colleagues explored the role of these receptors in LTP. in this paper, the answer is demonstrated as yes.
They show that in the presence of a glutamate antagonist, a stimulus which has the potential to generate an LTP response fails to be generated. There is no augmentation in the synaptic response. If you wash the drug away, you can produce an LTP response.
This experiment has been repeated thousands of times to give the same response. This shows that the NMDA receptor is responsible for the induction of LTP, but there must be some other glutamate receptor which may be responsible for the maintenance basal synaptic transmission.
Nowak et al 1984
Was able to show that the concentration of the external calcium ions had a profound effect on the performance of the NMDA receptor, such that under the resting and basal conditions, the receptor remained closed or inactive even if glutamate is bound to it. if the receptor was depolarised, the magnesium block is removed, and when the glutamate binds to the receptors, the receptor becomes conductive.
Basal transmission is mediated bu a second class of glutamate receptor
Evidence by Collingridge in 83 and Linda Novak in 84 it can be concluded that AMPA receptor is capable of passing a current and generating an EPSP irrespective of whether the cell is depolarised or not, however the NMDA would only allow the flux of ions to pass through it as and when the magnesium ion is displaced, which only occurs when the cell with the receptor is depolarised.
So the Hebbs postulate and work of Malenka ties these things together. Presynaptic activity is needed to deliver glutamate, and postsynaptic activity is needed to have enough activity to displace the magnesium block in the receptor. Only when these two things happen, there is LTP induction.
Teyler & DiScenna 1987
In a sense, cooperatively induced LTP is a special case of associative LTP: both originate from the requirement in the synchrony of inputs for postsynaptic activation
Levy & Steward (1983)
studied in more detail the temporal specificity in asso- ciative synaptic modification. By stimulating a weak and a strong input from theentorhinal cortex to the denate gyrus of hippocampus, they found that associative induction of LTP did not require perfectly synchronous activation of the two path- ways. Instead, the temporal order of the activation was crucial. LTP of the weak input could be induced when the strong input was activated concurrently with, or following the activation of, the weak input by as much as 20 ms. When the temporal order was reversed, long-term depression (LTD) was induced.
This and other early studies (Kelso & Brown 1986, Gustafsson & Wigstro ̈m 1986) have clearly indicated the existence of a stringent temporal specificity in the activity-induced synaptic modification.
NMDA receptors are conductive to more than one type of ion species
NMDA receptors can conduct sodium, calcium (which dont pass through AMPARs)
