Week 5: Hippocampus as Associative Memory Network Flashcards
Diagram of dorsal and ventral hippocampus in the rodent hippocampus
In the hippocampus, we have four principles areas (4)
- Hippocampus proper
- Dentate gyrus (DG)
- subiculum,
- and entorhinal area (EC)
What is the hippocampus proper made up of?
CA1, CA2 and CA3
The hippocampus is similar in
rodents and humans
The part of hippocampus that receives input from other areas of the brain is
EC (enthorine cortex)
The primary information processing pathway in the hippocampus is from the cortex into DG then
sends CA3,CA3 sends to CA1 and CA1 sends to SUB (subiculum)
The hippocampus is very similar across species as there is
similarities in mammals
There is similarities in mammals (mice, monkeys, humans)in their hippocampus as the - (2)
DG projects massively to CA3 (not vice versa)
CA3 projects massively to CA1 (not vice versa)
The Hopefield Network (HF) is known as the ‘toy’ model because this is a realistic model of a wiring diagram which is (2)
highly processed complex multisensory
it goes from unimodal primary sensory areas to polymodal association cortex
Polymodal association cortices where
Many different streams of information that converge on a neuron that is responsive to many different types of information
When sticking electrode in hippocampus we look at the
collective input
If we stick an electrode in the hippocampus when we are offline like resting and sleeping in which we
this could help (2)
We get ripples (high-frequency bouts of activity) the theta oscillations of membrane potential
which could help in consolidating and replaying memories
If we stick an electrode in the hippocampus when we tasks focused (online) while encoding and retrieving memories
we get these slow theta oscillations in the membrane potential
When we look at individual cells in the hippocampus proper we find cells called
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
Diagram of place cells (2)
Record a green dot every time that neuron recorded fires
Red represents maximal firing
When looking at individual cells in the EC cortex in hippocampus we find cells called
grid cells
grid cells are
Neurons that respond when an animal is in particular locations in an environment such that the responsive locations form a repeating grid-like pattern
Grid cells are important for
navigation and play an important role in memory
Diagram of grid cells
When looking at individual cells in hippocampus we also find head direction cells which
encode the heading of an animal
Diagram of HD cell plot
Diagram of HD cell plot
When we find individual cells in the hippocampus we find cells called boundary cells which
respond to the presence of an environmental boundary at a particular distance
There are boundary cells that fire boundaries at
east, west, south etc.. and for south west
Boundary cells appear to be related to
HD cells
Diagram of boundary cell
We know that the hippocampus is also important for spatial memory - (2)
e.g., Morris water maze
In Humans, taxi drivers in London have enlarged hippocampus by memorizing all of the streets
Hippocampus is a major area affected in
Alzheimer’s disease, vascular dementia, epilepsy
The degeneration of the hippocampus causes
deficits in spatial and episodic memory
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)
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
Case of HM in which had a and couldn’t (2)
surgery which removed his hippocampus to treat severe epilepsy
Subsequently unable to form new memories
According to Corkin (2013), HM had deficits in spatial memory as forgot locations of items and could not
find his way home
According to Corkin (2013) HM had deficits in spatial memory as he could not associate the what, where and when - (2)
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
It is the local connections which define the circuits or microcircuits that decdicated to one and e.g, (2)
or more specific functions
e.g., hippocampus has circuits dedicated to its function of associative memory
In DG, rats have about
1 million neurons
Perforant pathway connects to the cells in
DG as well direct connections to pyramidal neurons in the CA3 in the hippocampus
CA3 has
300,000 neurons in a rat (massive drop from DG)
The massive drop of number of rat neurons in DG to CA3 tells us
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
In CA3 there are recurrent connections
throughout the hippocampus
In CA1 there is 400, 000 neurons in
rat
Diagram of hippocampal circuit
Hippocampal circuit consists of (4)
- Mossy fibre
- Schafer and recurrent colalterals
- Perforant pathway
- Direct CA1 pathway
Mossy fibres
Connections from DG to CA3
schafer and recurrent collaterals
Connect CA3 cells among each other and then project to CA1 which also has place cells
The tri-synaptic loop in the hippocampus is the
connection of EC to DG to CA3 and CA1
We probably link the auto association memory store in hippocampus in the
CA3 area because of the dense recurrent connections
The hippocampal circuit can be redrawn like this also:
The mossy fibres from DG serve the function of in hippocampal circuit
denotator synapses
In addition of being able to impose activity pattern on CA3 and override recurrent connections, DG
performs a function called
pattern separation
pattern separation is opposite of
pattern completion
Pattern Separation in DG
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.
The overall function of DG
is poorly understood since it does not fire often
DG is the location of
adult neuro-gensis where new neurons are born
The CA3 extends across
the hippocampal circuit
Other parts of the circuit is more local (with local input), that is the CA1-CA3 connections
serve multiple roles
Multiple roles CA1-CA3 connection serve
First one is that it has the association of…
information-rich (EC-CA1) and information poor (compressed) in CA3 > CA1 streams
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
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)
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
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)
then mismatch can be indicator of changes in the environment
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
direct connection from EC to CA1 hetero-association generates a more information rich representation which is then associated to CA3
Auto association in ___ and hetero association in ___ and ___
CA3
CA3 and CA1
Summary of the hippocampal circuit as associative memory network (9)
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
Memories don’t depend on hippocampus forever as HM had intact memories of (3) but…
Old childhood memories undamaged
Memories from 5-10 years before lesions lost
Forgot death of favourite uncle in 1950
Since HM couldn’t retrieve the childhood memories he had before his suregrey it meant he had
retrograde amnesia
Retrograde amnesia (RA)
is a loss of memory-access to events that occurred, or information that was learned, before an injury or the onset of a disease.
temporal gradient of retrograde amnesia
Recall for events in the time immediately leading up to its onset very poor, but earlier memories relatively intact
Temporal gradient of retrograde amnesia shows that
memories depend on hippocampus temporally
The temporal gradient of retrograde amnesia and HM implies
hippocampal memories are consolidated in neocortex over time and therefore become hippocampal indepedent
There is fast and slow learning in memory consolidation in hippocampus
If we experience an event and memorise it then
Then learning event
(2)
hippocampal recurrent collaterals for rapid (;one-shot) associative learning
Then the hippocampus trains slow learning in neocortex and slowly update weights
Issues of fast and slow learning in memory consolidaiton (3)
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)
Model of fast and slow memory consolidation (2)
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
Model of consolidation of memory of how it happens
hot topic and ongoing debate
Place cells could be akin to the cells in hopefield network (5)
- At a given location a small number of them is active
- 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
- Provide a medium for pattern completion in CA3
- 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
