Lecture 2 - LTP and synaptic plasticity

Question 1

What changes in the brain change when we learn something?

Answer 1

More synapses

Changes in connectivity and strength of neurotransmission

Question 2

What is Hebb’s Postulate? (1949)

Answer 2

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)

Question 3

What happens in the hippocampus from the perforant path?

Answer 3

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

Question 4

Where do the inputs and outputs of the hippocampus flow through?

Answer 4

Perirhinal, Entorhinal and Postrhinal cortices

Question 5

Why is it much easier to figure out what is going on in the hippocampus than in the other cortices?

Answer 5

Hippocampus is extremely organised and layered whereas the others are not

Question 6

Who discovered LTP?

Answer 6

Bliss and Lomo (1973)

Question 7

What experiment did Bliss and Lomo perform? (1973)

Answer 7

Stimulated the perforant path

Recording at the synaptic area of granule neurons in the dentate gyrus

Question 8

What is a great thing about working on the hippocampus?

Answer 8

Can use one side as your control and one side as your experimental

Question 9

What did Bliss and Lomo see?

Answer 9

The perforant neurons pass through and contacted with a forest of dendrites of the dentate gyrus granule neurons

Question 10

How can you tell the difference between granule neurons and CA3/1s neurons?

Answer 10

Granule neurons are very small with small cell bodies whereas CA3/1s are giant

Question 11

What are the secondary neurotransmitter release sites all along the axon?

Answer 11

En passon synapses

Question 12

What projects onto the CA3 region and how do they tend to do it?

Answer 12

Mossy fibres from the dentate gyrus.

Tend to do it with a great big synapse at the end.

Question 13

What does epsp stand for?

Answer 13

Excitatory post synaptic potentials

Question 14

What happened when Bliss and Lomo dropped the electrode further down to where the cell bodies are?

Answer 14

They saw proper action potentials

Question 15

What was Bliss and Lomo’s experiment to find LTP and what were the results?

Answer 15

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.

Question 16

What two mechanisms do Bliss and Lomo suggest are responsible for LTP?

Answer 16

• An increase in the efficiency of synaptic transmission at the perforant path synapses.
• An increase in the excitability of the granule cell population.

Question 17

What is the specificity of LTP?

Answer 17

Inputs that are not active are not potentiated

Question 18

What is the co-operativity of LTP?

Answer 18

There is a threshold for induction - weak tetani activating very few fibres do not trigger LTP

Question 19

What is the associativity of LTP?

Answer 19

A weak input can be potentiated if active at the same time as a strong tetanus to a seperate but convergent input

Question 20

What are the differences between early LTP and late LTP?

Answer 20

Early:
Lasts hours and doesn’t require protein syn
Late:
Lasts days/weeks and requires protein syn

Question 21

What is cyclohexamide?

Answer 21

An inhibitor of protein synthesis

Question 22

What did Zalutsky and Nicoll (1990) do?

Answer 22

Stimulated the commissural pathway (connects CA3 regions of each side)
Took readings from CA1 neurons’ synapses

Question 23

What did Bashir et al (1991) do?

Answer 23

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.

Question 24

What kind of synapses are in the hippocampus?

Answer 24

Glutamatergic

Question 25

What can you do to prevent LTP?

Answer 25

Block AMPA receptors with CNQX

Question 26

What are the 2 switches of the NMDA receptors in LTP?

Answer 26

One is glutamate dependent

One depends on membrane potential

Question 27

What did Bashir show?

Answer 27

That LTP is associative - requires activity in both pre and post-synaptic terminals.
That LTP is co-operative - required activation of several SC axons together

Question 28

What happens if you record at the post synapse by the CA3 neurons?

Answer 28

Get a form of LTP which you can block NMDA but LTP still occurs

Question 29

What does this second type of LTP rely on?

Answer 29

Intracellular cAMP and Ca2+ signalling in presynapse

Increases neurotransmitter release

Question 30

What does forskolin do?

Answer 30

Activates adendyl cyclase giving lots of cAMP

Question 31

What did Weisskopf and Nicoll (1994) do with forskolin?

Answer 31

Added it to neurons and got LTP

Question 32

Is the second form of LTP associative?

Answer 32

No it only requires presynaptic activity

Question 33

What is the difference in the two types of LTP?

Answer 33

Normal LTP the pre-synapse changes

Second form of LTP the post-synapse changes