Week 5: Hippocampus as Associative Memory Network Flashcards

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1
Q

Diagram of dorsal and ventral hippocampus in the rodent hippocampus

A
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2
Q

In the hippocampus, we have four principles areas (4)

A
  1. Hippocampus proper
  2. Dentate gyrus (DG)
  3. subiculum,
  4. and entorhinal area (EC)
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3
Q

What is the hippocampus proper made up of?

A

CA1, CA2 and CA3

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4
Q

The hippocampus is similar in

A

rodents and humans

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5
Q

The part of hippocampus that receives input from other areas of the brain is

A

EC (enthorine cortex)

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6
Q

The primary information processing pathway in the hippocampus is from the cortex into DG then

A

sends CA3,CA3 sends to CA1 and CA1 sends to SUB (subiculum)

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7
Q

The hippocampus is very similar across species as there is

A

similarities in mammals

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8
Q

There is similarities in mammals (mice, monkeys, humans)in their hippocampus as the - (2)

A

DG projects massively to CA3 (not vice versa)

CA3 projects massively to CA1 (not vice versa)

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9
Q

The Hopefield Network (HF) is known as the ‘toy’ model because this is a realistic model of a wiring diagram which is (2)

A

highly processed complex multisensory

it goes from unimodal primary sensory areas to polymodal association cortex

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10
Q

Polymodal association cortices where

A

Many different streams of information that converge on a neuron that is responsive to many different types of information

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11
Q

When sticking electrode in hippocampus we look at the

A

collective input

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12
Q

If we stick an electrode in the hippocampus when we are offline like resting and sleeping in which we

this could help (2)

A

We get ripples (high-frequency bouts of activity) the theta oscillations of membrane potential

which could help in consolidating and replaying memories

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13
Q

If we stick an electrode in the hippocampus when we tasks focused (online) while encoding and retrieving memories

A

we get these slow theta oscillations in the membrane potential

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14
Q

When we look at individual cells in the hippocampus proper we find cells called

A

place cells which maximally response to specific locations in the world which is found from 10-20 minute single-cell recordings of mice travelling in box with food rewards

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15
Q

Diagram of place cells (2)

A

Record a green dot every time that neuron recorded fires

Red represents maximal firing

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16
Q

When looking at individual cells in the EC cortex in hippocampus we find cells called

A

grid cells

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17
Q

grid cells are

A

Neurons that respond when an animal is in particular locations in an environment such that the responsive locations form a repeating grid-like pattern

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18
Q

Grid cells are important for

A

navigation and play an important role in memory

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19
Q

Diagram of grid cells

A
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20
Q

When looking at individual cells in hippocampus we also find head direction cells which

A

encode the heading of an animal

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21
Q

Diagram of HD cell plot

A
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21
Q

Diagram of HD cell plot

A
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22
Q

When we find individual cells in the hippocampus we find cells called boundary cells which

A

respond to the presence of an environmental boundary at a particular distance

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23
Q

There are boundary cells that fire boundaries at

A

east, west, south etc.. and for south west

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24
Q

Boundary cells appear to be related to

A

HD cells

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25
Q

Diagram of boundary cell

A
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26
Q

We know that the hippocampus is also important for spatial memory - (2)

A

e.g., Morris water maze

In Humans, taxi drivers in London have enlarged hippocampus by memorizing all of the streets

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27
Q

Hippocampus is a major area affected in

A

Alzheimer’s disease, vascular dementia, epilepsy

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28
Q

The degeneration of the hippocampus causes

A

deficits in spatial and episodic memory

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29
Q

In animal models of Alzheimers where we can introduce the damage similar to seen in humans with Alzheimers and observed the activity of grid cells between them showed: (2)

A

The (grid) cells that expressed the spatial variables of where the animal is is affected in animal model of ALZ disease

further ponting to idea as damage to these kind of cells underly deficits in navigation

30
Q

Case of HM in which had a and couldn’t (2)

A

surgery which removed his hippocampus to treat severe epilepsy

Subsequently unable to form new memories

31
Q

According to Corkin (2013), HM had deficits in spatial memory as forgot locations of items and could not

A

find his way home

32
Q

According to Corkin (2013) HM had deficits in spatial memory as he could not associate the what, where and when - (2)

A

deficits in Hopfield network and memory matrices as those are an associative memory stores (perform pattern completion and identified with recall of memory)

Thus, HM couldn’t link elements together (what, where and when) anymore and subsequently recall them

33
Q

It is the local connections which define the circuits or microcircuits that decdicated to one and e.g, (2)

A

or more specific functions

e.g., hippocampus has circuits dedicated to its function of associative memory

34
Q

In DG, rats have about

A

1 million neurons

35
Q

Perforant pathway connects to the cells in

A

DG as well direct connections to pyramidal neurons in the CA3 in the hippocampus

36
Q

CA3 has

A

300,000 neurons in a rat (massive drop from DG)

37
Q

The massive drop of number of rat neurons in DG to CA3 tells us

A

incoming information coming from DG is more rich and detailed than CA3 meaning info has to be compressed down to a smaller number of neurons

38
Q

In CA3 there are recurrent connections

A

throughout the hippocampus

39
Q

In CA1 there is 400, 000 neurons in

A

rat

40
Q

Diagram of hippocampal circuit

A
41
Q

Hippocampal circuit consists of (4)

A
  • Mossy fibre
  • Schafer and recurrent colalterals
  • Perforant pathway
  • Direct CA1 pathway
42
Q

Mossy fibres

A

Connections from DG to CA3

43
Q

schafer and recurrent collaterals

A

Connect CA3 cells among each other and then project to CA1 which also has place cells

44
Q

The tri-synaptic loop in the hippocampus is the

A

connection of EC to DG to CA3 and CA1

45
Q

We probably link the auto association memory store in hippocampus in the

A

CA3 area because of the dense recurrent connections

46
Q

The hippocampal circuit can be redrawn like this also:

A
47
Q

The mossy fibres from DG serve the function of in hippocampal circuit

A

denotator synapses

48
Q

In addition of being able to impose activity pattern on CA3 and override recurrent connections, DG
performs a function called

A

pattern separation

49
Q

pattern separation is opposite of

A

pattern completion

50
Q

Pattern Separation in DG

A

if two incoming neural patterns are fairly similar (i.e., a large proportion of the same neurons active at the same), then DG makes these patterns dis-similar.

51
Q

The overall function of DG

A

is poorly understood since it does not fire often

52
Q

DG is the location of

A

adult neuro-gensis where new neurons are born

53
Q

The CA3 extends across

A

the hippocampal circuit

54
Q

Other parts of the circuit is more local (with local input), that is the CA1-CA3 connections

A

serve multiple roles

55
Q

Multiple roles CA1-CA3 connection serve

First one is that it has the association of…

A

information-rich (EC-CA1) and information poor (compressed) in CA3 > CA1 streams

56
Q

Multiple roles CA1-CA3 connection serve

Second one is that different information enters the hippocampal circuit at different dorso-ventral level but CA3

A

extends along the entire longitudinal axis of the hippocampus

57
Q

Multiple roles CA1-CA3 connection serve

Second one is that different information enters the hippocampal circuit at different dorso-ventral level but CA3 extends along the entire longitudinal axis of the hippocampus -example: (2)

A

At one dorso-ventral level information about the affective state may enter (e.g., fear).

At another dorso-ventral level spatial information may enter (e.g., where was I in the enviroment). CA3 synapses can associate affective and spatial information

58
Q

Multiple roles CA1-CA3 connection serve

Third is during recall if EC CA1 connection produces one pattern in CA1 but the CA3>CA1 connection produces a slightly different pattern from memory (via pattern completion in CA3)

A

then mismatch can be indicator of changes in the environment

59
Q

At the same time of encoding memory in CA3, Since information is compressed when it goes to CA3, you still want to retrieve a lot of detail so

A

direct connection from EC to CA1 hetero-association generates a more information rich representation which is then associated to CA3

60
Q

Auto association in ___ and hetero association in ___ and ___

A

CA3
CA3 and CA1

61
Q

Summary of the hippocampal circuit as associative memory network (9)

A

1) Perfornant path synapes in DG form new representations of input from EC

2) Mossy fibres from DG to CA3 induce a sparse pattern of activity for auto-associative storage

3) Excitatory recurrent connections in CA3 mediate auto-associative storage and recall of these patterns

4) Schaffer collaterals from region CA3 to CA1 meditate hetero-associative storage and recall of associations between activity patterns in CA3 and activity induced in CA1 by entorhinal input

5,6) Perfornant path inputs to region in CA1 form a new representations of entorhinal cortex input for comparisson/association with recall from CA3

7,8) The comparison of recall activity in region CA3 with direct input to region CA1 regulates cholinergic modulation. Mismatch between recall and input increases ACh, match decreases ACh

9) The theta rhythm may time encoding vs retrieval modes

62
Q

Memories don’t depend on hippocampus forever as HM had intact memories of (3) but…

A

Old childhood memories undamaged

Memories from 5-10 years before lesions lost

Forgot death of favourite uncle in 1950

63
Q

Since HM couldn’t retrieve the childhood memories he had before his suregrey it meant he had

A

retrograde amnesia

64
Q

Retrograde amnesia (RA)

A

is a loss of memory-access to events that occurred, or information that was learned, before an injury or the onset of a disease.

65
Q

temporal gradient of retrograde amnesia

A

Recall for events in the time immediately leading up to its onset very poor, but earlier memories relatively intact

66
Q

Temporal gradient of retrograde amnesia shows that

A

memories depend on hippocampus temporally

67
Q

The temporal gradient of retrograde amnesia and HM implies

A

hippocampal memories are consolidated in neocortex over time and therefore become hippocampal indepedent

68
Q

There is fast and slow learning in memory consolidation in hippocampus

If we experience an event and memorise it then

Then learning event

(2)

A

hippocampal recurrent collaterals for rapid (;one-shot) associative learning

Then the hippocampus trains slow learning in neocortex and slowly update weights

69
Q

Issues of fast and slow learning in memory consolidaiton (3)

A

Issues of fast and slow learning in memory consolidaiton

How exactly is this rehearsal happening

and how fast is this transfer? (One night or 20 years)

70
Q

Model of fast and slow memory consolidation (2)

A

Form strong connections in CA3 to be able to pattern complete to cortex

Overtime, the connections in hippocampus wil decay away once you established strong connections in cortex

71
Q

Model of consolidation of memory of how it happens

A

hot topic and ongoing debate

72
Q

Place cells could be akin to the cells in hopefield network (5)

A
  1. At a given location a small number of them is active
  2. Using Place cells in CA3 and other cells outside hippocampus (e.g., code for affective state/intention) to Associate together (i.e., bind) the inputs related to an event that is available in from a given location
  3. Provide a medium for pattern completion in CA3
  4. At a given location by forming these connections, an attractor is formed across CA3,consisting of spatial and non-spatial information.
    5.When position changes, a new set of place cells is active, and a new associations is retrieved