Lecture 2 - LTP and synaptic plasticity Flashcards
What changes in the brain change when we learn something?
More synapses
Changes in connectivity and strength of neurotransmission
What is Hebb’s Postulate? (1949)
When an axon of cell A is near enough to excite cell B and repeatedly 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. (neurons that fire together, wise together)
What happens in the hippocampus from the perforant path?
Perforant path (from entorhinal) projects onto mossy fibres
Mossy fibres project onto CA3 region through the dentate gyrus
CA3 projects on the CA1
CA1 has various outputs
Where do the inputs and outputs of the hippocampus flow through?
Perirhinal, Entorhinal and Postrhinal cortices
Why is it much easier to figure out what is going on in the hippocampus than in the other cortices?
Hippocampus is extremely organised and layered whereas the others are not
Who discovered LTP?
Bliss and Lomo (1973)
What experiment did Bliss and Lomo perform? (1973)
Stimulated the perforant path
Recording at the synaptic area of granule neurons in the dentate gyrus
What is a great thing about working on the hippocampus?
Can use one side as your control and one side as your experimental
What did Bliss and Lomo see?
The perforant neurons pass through and contacted with a forest of dendrites of the dentate gyrus granule neurons
How can you tell the difference between granule neurons and CA3/1s neurons?
Granule neurons are very small with small cell bodies whereas CA3/1s are giant
What are the secondary neurotransmitter release sites all along the axon?
En passon synapses
What projects onto the CA3 region and how do they tend to do it?
Mossy fibres from the dentate gyrus.
Tend to do it with a great big synapse at the end.
What does epsp stand for?
Excitatory post synaptic potentials
What happened when Bliss and Lomo dropped the electrode further down to where the cell bodies are?
They saw proper action potentials
What was Bliss and Lomo’s experiment to find LTP and what were the results?
Sample the background level of activity by stimulating with a single pulse (1Hz). Then plot the activity. Record every 3-5 minutes.
Then a very large stimulus (100Hz for 3 seconds) mimicking learning stimulus.
Basal level increased after the large stimulus.
Repeated large stimulus and got increase and stability every time.
Got stable results of LTP for hours, some people have had it for months.
What two mechanisms do Bliss and Lomo suggest are responsible for LTP?
- An increase in the efficiency of synaptic transmission at the perforant path synapses.
- An increase in the excitability of the granule cell population.
What is the specificity of LTP?
Inputs that are not active are not potentiated
What is the co-operativity of LTP?
There is a threshold for induction - weak tetani activating very few fibres do not trigger LTP
What is the associativity of LTP?
A weak input can be potentiated if active at the same time as a strong tetanus to a seperate but convergent input
What are the differences between early LTP and late LTP?
Early:
Lasts hours and doesn’t require protein syn
Late:
Lasts days/weeks and requires protein syn
What is cyclohexamide?
An inhibitor of protein synthesis
What did Zalutsky and Nicoll (1990) do?
Stimulated the commissural pathway (connects CA3 regions of each side)
Took readings from CA1 neurons’ synapses
What did Bashir et al (1991) do?
Did a patch clamp with a perforated (with nystatin which makes holes in membranes) membrane.
Then inhibited AMPA receptor currents and looked at trace.
Then Inhibited GABAergic inhibitory currents using picrotoxin.
Then added AP5 which blocks NMDA receptors blocking the current.
What kind of synapses are in the hippocampus?
Glutamatergic
