The hippocampus is a key brain circuit for
certain forms of memory
Anterograde amnesia
Retrograde amnesia
Events
Places
H.M. (Henry Gustav
Molaison, 1926–2008)
“(…) After operation this young man could no longer recognize the hospital staff nor find his way to the
bathroom, and he seemed to recall nothing of the day-to-day events of his hospital life. (…) he did not
remember the death of a favourite uncle three years previously (…). The family moved from their old house
to a new one a few blocks away on the same street; he still has not learned the new address, though
remembering the old one perfectly, nor can he be trusted to find his way home alone. (…) This patient has
even eaten luncheon in front of one of us (…), a mere half-hour later (…) he could not remember having
eaten luncheon at all. Yet to a casual observer this man seems like a relatively normal individual, since his
understanding and reasoning are undiminished.”
in Scoville and Milner, 1957
Brenda Milner, Larry R. Squire,
and Eric R. Kandel Neuron, Vol.
20, 445–468, March, 1998
Short term Memory:
•Immediate Memory
•Working Memory
Long Term Memory (Hours/Days/Years)
Immediate Memory
‐Current attention or stream of thought 7±2 items
-Persists for less than 30 seconds
Working Memory
‐An extension of immediate memory extended in time
‐Can last for several minutes if contents are actively rehearsed.
Declarative Memory can be divided further:
Semantic Memory
‐World knowledge. Memory for facts.
‐Recall of a fact or item.
Episodic Memory
‐Memory of past events.
‐Autobiographical memory
‐Information about what , where, and
when an event occurred
Episodic memory is often organised along sequences of events.
We remember the order in which events occurred, not
necessarily their exact time.
In the Morris water maze the animal learns
the location of a hidden escape platform
(delayed match to place task, Morris, Garrud,
Rawlins, O'Keefe J, 1982, Nature)
This task encapsulates many aspects of
episodic memory:
-1 trial learning
-incorporates the ‘where’ aspect of memory
This task require the hippocampus
It demonstrates that the hippocampus is
important for spatial navigation
Link with physiology: place cells
The hippocampus is a key brain circuit for
certain forms of memory
Learning trials
Post-learning probe
test (no platform)
Glutamate-receptor-mediated encoding and
retrieval of paired-associate learning
M. Day, R. Langston and R. G. M. Morris
Nature 424, 205-209
Western scrub-jay posses episodic-like memories
Clayton and Dickinson, 1998, Nature
Western scrub-jay that cache different types of food for later use (what-where-when
aspect of the hidden food)
Hippocampus is involved in the coding of sequences
Norbert J. Fortin, Kara L. Agster and Howard B. Eichenbaumnature neuroscience • volume 5 no 5 • may 2002
The hippocampus is also involved in short-term memory. Some place cells fire in
relation to the memory task. Gamma oscillations may have a special role
Wood et al., Neuron, 2000
Montgomery et al., PNAS, 2007
Sleep reactivation
•
New memories are needed to be integrated into
existing representations during consolidation – this
process is slower than memory acquisition
•
An intermediate memory store is needed, which
would enable the subsequent replay of previously
stored memory traces (Mar, 1971)
•
It has been suggested that the hippocampus acts as
an intermediate store and that reactivation of
stored memory traces takes place in subsequent
sleep. Reactivation enables the transfer of
reactivated patterns to extra-hippocampal locations
for long-term storage (Buzsaki, 1989; McClelland,
McNaughton & O'Reilly 1995)
•
The waking activity patterns of hippocampal
neurons recur in subsequent sleep (Wilson and
McNaughton, 1995). Acquisition and replay of these
patterns are associated with different network
patterns occurring in different behavioural states
Dali, The Persistence of Memory 1931
O’Neill et al., Nat. Neurosci. Cover 2008
Finger tapping task
Recall of certain memories is better after sleep: the role of
sleep in consolidation
Slow wave sleep facilitates the recall of learnt words
Marshall, Helgadottir H, Molle M, Born J, Nature (2006)
Ngo et al., Neuron 2013
Place cells
Hippocampal principal cells fire in relation to space and together they
form a cognitive map of the environment (O’Keefe and Nadel, 1978)
Y-Position (cm)
100
Firing rate (Hz)
16
80
12
8
60
4
0
40
20
0
0
20
40
60
80
X-Position (cm)
100
We record in parallel from many place cells
Theta phase precession
• The spike timing of place cells relative to
theta oscillation encode place on the linear
track
wall
food
foo
d
wall
1
8
3
7
6 4
5
2
1
Spikes fired (single run)
2 3 4 5
6 7
8
O’Keefe & Recce, Hippocampus, 19
Skaggs et al., Hippocampus, 1996
Different network patterns during waking exploration and sleep are involved
in the acquisition and replay of memory traces of waking experience
sharp wave/ripple (SWR)
theta
◄
Exploration
SWR
and REM sleep
slow-wave sleep
and immobility,
consummatory
behaviours
►
place cells
‘storage’ of place cell
firing patterns
replay waking patterns
The joint firing patterns of hippocampal cells are reactivated in
subsequent sleep
O’Neill, Senior, Allen, Huxter Csicsvari, Nat. Neurosci. 2008
Test whether cofiring during exploration is related to cofiring during
sleep
cells a
and b
Cofiring
Exploration
100 ms
Cofiring between cell-pairs was measured
as the correlation coefficient of spikecounts measured in 100ms windows
Sleep
Cofiring
cells a
and b
50ms
100 ms
Place cells that fire together during exploration also fire
together during sleeping sharp wave/ripples (sSWR)
Cell pair co-firing (exploration vs. post-sleep)
0.4
0.3
0.2
0.5
0.1
P<0.001
0.1 0.15
0.2
0.25
Co-firing during exploration (r)
0.3
0.2
0.1
P<0.001
sS W R
0.05
po st -
0
0.3
sS W R
-0.05
0.4
p re -
0
Correlation coefficient
Co-firing during sleep (r)
0.5
0
Co-firing during theta vs. SWR
Wilson and McNaughton, 1995;
Kudrimoti et al. 1999; Hirase et al. 1999;
O’Neill, Senior, Csicsvari, Neuron, 2006
Cells with similar place fields also fire together in post-sleep
O’Neill, Pleydell-Bouverie, Dupret & Csicsvari, TINS, 2010
0.5
0.6
Correlation coefficient
Cofiring during Sleep (r)
0.7
0.5
0.4
0.3
0.2
0.1
0
-0.1
0.4
0.2
0.1
0
-0.2
-0.3
-0.4
-0.8 -0.6 -0.4 -0.2
0
0.2
0.4
0.6
Place field similarity (r)
0.8
1
P<0.001
0.3
P<0.001
pre-sleep
post-sleep
O’Neill, Senior, Csicsvari, Neuron, 2006
Wilson and McNaughton, 1995
• place cells fire sequentially during each theta cycle,
encoding the movement path of the animal
• these sequences are also reactivated during sleep
Firing sequences during theta oscillations represent
movement paths - even in 2D environments
Firing sequences of place cells are
reactivated during sleep
Huxter, Allen, Senior, Csicsvari, Nat. Neurosci., 2008
Lee and Wilson, Neuron, 2002
Assessing spatial memory on the cheeseboard
maze
Place learning task on the cheese board maze
Every day the animal has to learn 3 new reward locations
probe trial
learning trial
encoding
consolidation
recall
Dupret, O’Neill, Pleydell-Bouverie and Csicsvari, Nat. Neurosci, 2010
Learning and remembering the positions of new goal
locations
Dupret, O’Neill, Pleydell-Bouverie and Csicsvari, Nat. Neurosci, 2010
Learning
Probe
Probe
CA1
CA3
Dupret, O’Neill, Pleydell-Bouverie and Csicsvari, Nat. Neurosci, 2010
Reactivation of goal-related patterns predict
subsequent memory performances
Dupret, O’Neill, Pleydell-Bouverie and Csicsvari, Nat. Neurosci, 2010