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Molecular and Cellular Neuroscience > Plasticity In The Hippocampus > Flashcards

Plasticity In The Hippocampus Flashcards

1
Q

Where is the hippocampus?

A

Medial temporal lobe

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2
Q

From medial to lateral name the structure of the medial temporal lobe?

A

Hippocampus
Enterhinnal cortex
Perihinnal Cortez
Parahippocampal cortex

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3
Q

Why is the entorhinal cortex important?

A

Sends projections to the hippocampus
Contains grid cells which are active when rat is in multiple locations
When rat navigates around the clock in different locations some grid cells would become more active than others
Send signals to place cells in hippocampus

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4
Q

How are memories formed (grossly)?

A

Sensory information
Processed by cortical association areas
Sent to parahippocampal and entorhinal cortical areas

To hippocampus (back to engram cells in respective cortical association areas in loop AND Hippocampus to the thalamus and hypothalamus via the fornix)

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5
Q

What are the synapses in the trisynaptic pathway?

A

EC (perforant path) - granular cells in dentate gyrus
Mossy fibres (axons of granular cells) - pyramidal cells in CA3
CA3 - CA1

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6
Q

What 2 pathways go from ca3 to ca1? What’s the difference?

A

Schaffer collateral fibres projects to CA1 from ipsilateral hippocampus CA3 region

Associational commissural fibres project to CA1 from contralateral CA3

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7
Q

What does the CA in CA1 and 3 mean?

A

Cornu ammonis (rams horn)

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8
Q

What layers of the entorhinal cortex makes up most of the perforated path?

A

2 and 3

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9
Q

The perforated path is made from a medial section and lateral section. Where do they originate and terminate?

A

Medial - layers 2 and 4 to dentate gyrus

Lateral - layers 3 and 5 bipass the dentate gyrus and synapse on CA3 neurons

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10
Q

Where do CA1 neurons project to?

A

Proximal CA1 neurons to distal subiculum

Distal ca1 neurons to proximal subiculum

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11
Q

Where do neurons within the subiculum project to?

A

Proximal subiculum to medial EC
Distal subiculum to lateral EC

2 closed loops are formed as the distal subiculum received lateral EC inputs
Proximal subiculum receives medial EC inputs

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12
Q

What are the functions of the hippocampus?

A 
Behavioural inhibition (removal = behavioural inhibition in animals)
Memory 
Spatial map - place cells
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13
Q

What are place cells?

A

The GPS of the brain
Particular neurons in the hippocampus fire when we are in a particular location ‘place field’

Based on visual cues AND where we think we are in space (if familiar with the location)
PET scans of humans navigating through a video game show hippocampal activity

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14
Q

Who first discover LTP?

A

Bliss and lomo 1973
In the hippocampus of rabbit brains
Between perforant path and dentate gyrus

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15
Q

Experimentally how can LTP be produced?

A

Theta burst stimulation
3 trains of stimuli 20 seconds apart
Each train consists of 10 stimulus epochs delivered at 5Hz (200ms apart)
Each epoch consists of 4 pulses at 100Hz

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16
Q

What are the 4 properties of LTP?

A

Cooperativity
Persistence
Input specific
Associativity

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17
Q

What is meant by LTP cooperativity?

A

Weaker spacial summation of multiple synaptic inputs can induce an action potential. Synapses which contribute to this AP will be potentiated.

18
Q

What is meant by spike time dependant plasticity?

A

LTP will occur if and action potential occurs within 100ms of transmitter release, important for cooperativity

As the synapses which contributes to the AP will be potentiated.

If Inout occurs after postsynaptic AP FIRING that will be depressed

19
Q

What is meant by persistence?

A

LTP can last for hours/days/months
Due to protein synthesis and structural changes in the synapse
Role of PKM(Zeta)

20
Q

What is meant by input specific LTP?

A

LTP Occurs only at synapses which are activated

Synaptic tag?

21
Q

What is associativity?

A

A strong stimulus will potentiate a weaker stimulus if an AP is induced. Contributing fibres and post synaptic cell need to be activated together.
Therefore, the weaker input following potentiation may be able to induce an AP alone (could not do so before potentiation by sting input)
Thus the the strong input is now associated with the previous weak input

22
Q

What learning theory is associativity associated with?

A

Classical conditioning
The strong input and weak input have been associated together as following potentiation both can cause an action potential in the same post synaptic cell

23
Q

What feature of NMDAR/ makes them a ‘coincidence detector’?

A

They detect both change in post synaptic membrane potential AND glutamate release

24
Q

What is the importance is AMPAR mediated depolarisation and NMDAR function?

A

Extent of depolarisation mediated by AMPARS control the extent of mg2+ release from NMDARs. Therefore, it governs the amount of calcium entry
Low levels active phosphatases (LTD)
High levels activate kinases (LTP)

25
Q

What does CaMKII stand for?

A

Calcium/ calmodulin dependant protein kinase

26
Q

What type of study showed that CaMKII moves into synapse following LTP?

A

Glutamate uncaging studies with a CaMKII sensor camui

27
Q

What is the function of CaMKII in LTP?

A

Phosphorylates stargazin which mobilises AMPARS to synapse (increases AMPAR levels)
Phosphorylates S831 on GluA1 which causes an increase in channel conductance (increased ion flux for same amount for transmitter)
Binds to NMDAR GluN2B subunit which prolongs CaMKII activation state - prevents autoinhibitory actions

28
Q

What are the ca2+/calmodulin sensitive variants of adenylyl cyclase?

A

AC1 sensitive to ca2+/calmodulin (increases activity)

AC5 sensitive to calcium (decreases activity)

29
Q

What does the increase in PKA as a result of LTP achieve?

A

Phosphorylates camp response element binding protein either directly or through increase in MAPK signalling

Phosphorylated CREB then activates camp response element (CRE) which causes gene transcription for various growth factors which mediate spine formation

30
Q

What different forms of synapse are formed by LTP?

A

Perforated synapses (fenestrated -> horseshoe -> segmented -> 2xsimple

Moves from 1 simple synapse through the perforated synapses to 2 x simple

31
Q

What is a perforated synapse?

A

When the post synaptic cell has discontinuity of its PSD

32
Q

Has change in spine anatomy been observed experimentally?

A

Yes, in vivo experiments following learning or procedure training in rats

33
Q

What are the different types of synaptogenesis?

A

A spine with multiple inputs
1 Presynaptic terminal to multiple spines
Bifurcation of spines
Enlargement of spine heads

34
Q

On a stimulus to induce LTD what happens to spines?

A

Decrease in spine growth

Increase in spine elimination

35
Q

Why must synapogenesis be a mechanism of later LTP?

How long to synapses take to mature?

A

Spines take too long to form therefore are not the mechanism of LTP in the short term
In vitro studies show spine growth can take between 5-19 hours to be fully matured after the formation of protrusion

36
Q

What is hypothesised to contribute to spine stability?

A

Formation of a PSD

37
Q

Why is PKM(zeta) important?

A

PkmZ is a PKC isoform shown experimentally to be important for longer term memory consolidation. Blocking its function e.g. Via pseudosubstrate ZIP injected into the hippocampus in Vigo attenuates LTP and also memory formation to avoid a shock platform

38
Q

Who conducted the experiment to show LTP is important in memory?

A

Tsien et al 1996

39
Q

How did tsien et al 1996 show LTP is important in memeory?

A

Selective KO of GluN1 NMDAR subunit in pyramidal Ca1 neurons
Causes loss of LTP and deactivation of NMDAR current in CA1 neurons
Showed impairment of spacial memory as tested by Morris water maze test ( take longer to find plateform compared to WT whose time continually decreases and plateaus)

40
Q

Do GluN1 KO mice show impairment in Morris water maze test in the presence of the plateform signal?

A

No, therefore the increased time taken to locate the hidden platform only due to impairment of spacial memory

Molecular and Cellular Neuroscience (11 decks)

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