major studies

Question 1

Wood (2000)

Answer 1

task 2 - relation spatial representation and memory

task/method: tmaze

experimental condition: experiment that would record cell activity when
animal was doing a “path” and would have to choose to turn left or right

results:
place cells can modulate their activity depending on whether an
animal will turn left or right in the future - In essence, the place cells have
a predictive code, signalling intended destination – this shows predictive
coding

Question 2

klaus (2013)

Answer 2

task 2 - relation spatial representation and memory

task/method: t maze

experimental condition:
animal runs in a treadmill
and then has to decide to turn left or right – Place cells can also show a
time signal - If animals have to run on a treadmill for a fixed period of
time, different place cells will prefer to fire at different time points on
the treadmill

results:
cells fire at the beginning of the run, other cells in the
middle of the run and some other different ones at the end – this shows
temporal coding

Question 3

aranov (2017)

Answer 3

task 2 - relation spatial representation and memory

task/method: conditioning paradigm 
experimental condition:
animal needs to hold
lever down until it hears a sound, then it needs to
release

results: they found that place cells can also
develop a preference for different non-spatial
variables – such as tones! - Grid cells could
similarly adopt such auditory tuning but with
multiple firings as compared to place cells – this
shows auditory coding (cells respond to a tone of
a particular frequency)

Question 4

kim and faselow (1992)

Answer 4

task 3 - consolidation

task/method:
experimental condition:
results:

Question 5

wilson and mcnaughton (1994)

Answer 5

task 3 - hebbian plasticity

task/method: z maze
experimental condition:
results: they observed
place cells with overlapping fields in an environment tended to be active
together in subsequent sleep
- They proposed that through repeated reactivation of wakeful activity patterns,
new memories become consolidated (through Hebbian plasticity) and committed to long-term storage in the cortex.

Question 6

olafsdottir (2016)

Answer 6

task 3 - replay for memory consolidation

task/method:
experimental condition:
results:

Question 7

foster and wilson (2006)

Answer 7

task 3 - replay for memory consolidation

task/method:
experimental condition:
results: replay events occur more frequently during novel
experience.

• replay in memory consolidation is consistent with
  SWRs occuring more frequently after rewarded runs
  (more memory consolidation) vs unrewarded runs
• increase in reverse replay is driven by rewarded
  experiences – suggest reverse reply is involved in learning (ambrose, 2016)

Question 8

girardeau (2009)

Answer 8

task 3 - replay for memory consolidation

task/method: radial arm maze

experimental condition: animal learns to locate food in 3
or 8 arms , then they sleep and they
either disrupt SWRs or not (some other
brain activity is disrupted).
results: swr ripples disruption impairs acquisition of a novel spatial memory task - provides casual evidence for the role
of replay in consolidation

Question 9

maingret (2016)

Answer 9

task 3 - replay for memory consolidation

• provides casual evidence for the role of replay in consolidation
• replay is associated with higher communication btw hippo
  and cortex – assessed here by measuring oscillatory coupling
  during sleep that is associated with learning
• trained animals on object rotation – free to explore objects in
  environment then animals sleep and then they’re put in the
  same environment but one of the objects moved, if the animal
  notices it will go there to explore otherwise the animal does
  not recall. Recall was successful for group that had 20 minutes
  encoding period, but not for the 3 minutes encoding period.
  Only for the 20 minutes group they found oscillatory coupling
  btw hippo and cortex (= co-occurrence of ripples, spindles and
  delta waves occurring in close temporal proximity during
  sleep)

- Spatial memory learning is
supported by coupling between
hippocampal and cortical
oscillations during sleep
- Artificially inducing oscillatory
coupling between the
hippocampus and cortex during
rest can create a long-lasting
spatial memory

Question 10

gridchyn (2020)

Answer 10

task 3 - replay for memory consolidation

memory targeted relay disruption leads to impaired recall of targeted memories ONLY

- one of the most important
experiments in the field
- animals navigate in either a
control or target circular
environment, which are very similar
and they have to locate a reward,
after 4 hours of sleep (controls get
no optogenetic disruption and
experimentals get opto disruption)
they explore the environment again
but no reward is located (do
animals spend more time in the
location where there was previously
food or not?

Question 11

singer (2013)

Answer 11

task 3 - replay for planning

on a WM task cells were more likely to be active in swr during swrs preceding correct decisions BUT only during initial learning of the task

• replay during working memory task
  (double-u shape mazes)
• early in training there were more SWRs
  overall for correct trials

Question 12

jadhav (2012)

Answer 12

task 3 - replay for planning

disrupting swrs only affects memory guided decision on a wm task

• if you disrupt ripples then their
  performance is worse
• WM is main support for planning function of
  replay

Question 13

olafsdottir (2017)

Answer 13

task 3 - replay for planning

Just before an animal initiates a goal-directed trajectory or the animal has just reached a
reward location, replay preferentially depicts task-focused information.
• However, if the animal disengages from the task, replay shows no biases
• Thus, replay may switch between planning and consolidation in response to task demands

During engaged periods, the
replay also preferentially depicted
local, congruent and forward
replay trajectories
• However, during engaged periods
preceding incorrect decisions no
biases in engaged replay were
observed

• when they go on track 2 or 3 they have
  different brain raresentations
• as the animal arrived to the corner there was
  a very strong bias for replay that was
  depicting locations near the animal, this bias
  disappeared if the animal linger that corner
  (stays long in that corner)
• replay seems to switch between planning
  and consolidation mode depending how
  engaged the animal was to the task
• bias was looking at what was being replayed,
  either remote (far) or local (close) locations
• if they made a mistake they won’t be
  rewarded (incorrect) – no bias (engaged
  error = disengaged correct and error)

Question 14

pfeiffer (2013)

Answer 14

task 3 - replay for planning

- animals navigate in rectangular
environment where they had to locate
food , every day food was in a
different location
- there were either goal-directed trials
(food appears in same location) or
random foraring trials (food appears in
random location)
- they predicted what the animal was

going to do before initiating a goal-
directed trajectory

During a goal-directed navigation
task rat haves to alternate between
foraging for food and running to a
known goal location
• Before animals initiate a goal-
directed trajectory, replay seems
to depict the animal’s upcoming
trajectory
• However, before random
trajectories, replay events do not
predict what path the animal will
take

Question 15

gupta (2010)

Answer 15

task 3 - replay for immagination

• animals follow a T maze (the dotted one
  is imagination that is a shortcut to a goal)
• they found replay in the task, when
  animal was located in a reward location
  but also depict never experienced paths

replay depict never experienced paths (i.e. shortcuts

Question 16

olafsdottir (2015)

Answer 16

task 3 - replay for immagination

• animal is put in a T maze but can’t reach
  its arms because there is a transparent
  barrier, in one of the arms food is placed
  but animal can’t reach it. Then animal
  sleeps and then does T maze with no
  barrier

Replay can also pre-play paths in
unexplored environments
• However, preplay only found for
novel environments seen before
and only for paths leading to a
goal

Question 17

green (1982)

Answer 17

task 4 - memory emergence in first years of life

Rat pups can successfully carry out a working
memory task from ~3weeks of age
• However, short-term reference memory (which does
not require the hippocampus) can be carried out by
2week of animals

Similar to humans, rodents show protracted development of episodic/spatial memory.
• As rodents age, the interval over which they can retain new learning increases

Question 18

vargha (2001)

Answer 18

task 4 - memory emergence in first years of life

 Although episodic declarative memory
may develop gradually, the developmental
timeline of semantic declarative memory
may be different
• Developmental amnesia patients can form
new semantic memories despite extensive
hippocampal lesions and severely impaired
episodic memory function
• Semantic memory may be mature at birth
OR developmental amnesia is associated
with alternate mechanisms of semantic
memory formation

• It could be, we’re not sure yet

Question 19

guskjolen (2018)

Answer 19

task 4 - memory emergence in first years of life

task 4 - memory emergence in first years of life

- used contextual fear conditioning task
and labelled cells that were active during
the encoding in infant animal, then
artificially reactivate them when the
animal is older doing the same task the
memory is recovered – episodic recall
hasn’t developed yet in infant 

Memories formed during the infantile amnesia period
can be recovered if the original memory trace is
‘synthetically’ re-activated.
• Suggest, perhaps, infantile amnesia reflects a retrieval
deficit

Question 20

donato (2017)

Answer 20

task 4 - stellate cells

Different sub-regions of the hippocampal formation
show distinct developmental timelines
• The superficial layers of the entorhinal cortex(EC)
develop first, followed by CA3/CA2 and CA1
• The deep layers of the EC and the dentate gyrus are
the last to develop
• These findings have been observed both in monkeys
and rodents

• CA2 is the first one to develop, then CA3 and
  CA1 (which have numerous developing times,
  depending on the area) and then the dentate
  gyrus
• Donato paper: entorhinal stellate cells
  provide an activity-dependent instructive
  signal that drives maturation sequentially and
  uni-directionally through the intrinsic circuits
  of the entorhinal-hippocampal network. The
  findings raise the possibility that a small
  number of autonomously developing neuronal
  populations operate as intrinsic drivers of
  maturation across widespread regions of the
  cortex

Question 21

wiltgen (2010)

Answer 21

task 6 - semantic memory in rodents

• semantic memories differ in quality as
  they’re gist like – gist tested with fear
  conditioning in context A , then there is
  context B which is quite similar to A and then
  C is very different from A and B – animals
  generalize fear more to context B than C over
  time which means they’re discriminating less
  context A and B – if hippo is shut off then
  generalization still happens – shows that
  semantic memories are cortex dependent and
  hippo independent
• this model uses fear conditioning which is
  not an adequate model as if animal is familiar

with context a and b before fear conditioning, then animal would be able to discriminate

Question 22

yonelinas (2005)

Answer 22

task 6 - semantic memory in rodents

• Roc curves – means receiver operating characteristic curve – it is a graph that shows the performance of a
  classification model at all classification thresholds
• familiarity would be semantic (cortical) and recollection (perfectly remembering something) would be hippocampal
  – this is easy in humans (they ask) but not in rodents
• mind the definition of roc on the slide. – if familiarity is used as a strategy then there is a curved line , while if you
  use recollection there would be a straight line in the plot

Question 23

liang (1986)

Answer 23

task 8 - how stress influences memory

Role of epinephrine – How does it enhance memory?
If you block NE in amygdala, does it mean E effect on memory blocks too? Yup – this
study showed that by blocking E with propranolol retention latency decreases

Question 24

quirarte (1997)

Answer 24

task 8 - how stress influences memory

Interaction between NE and GLUCORTICOIDS – how?
Dexamethasone: syntetic glucorticoid
Did same experiement as before but instead of NE they give glucorticoids – similar
results!

What does it mean?
If glu need NE and NE is realeased in arousal conditons then do glu modulate NE only
during arousal conditions? – do effects on memory of glu interact with emotional
arousal?

Question 25

roozendaal (2006)

Answer 25

task 8 - how stress influences memory

Interaction between NE and GLUCORTICOIDS – how?
They want to know if NA is necessary for the effects of glu on memory
Object recognition task – first day gets used to two objects then in second day one is
replaced with a new object – if the animal spends more time on new object it means
it remembered the old one
Two conditions: one with stress and one without.
– to put a rat in a box is already stressful so they habituated them first (top right
figure) for one out of two conditions
Without habituation (NO STRESS)
- Memory is enhanced by glu and it has an interaction with NE as memory is
suppressed by propranolol (beta blocker)
With habituation (STRESS)
- Memory is not enhanced – meaning that glu (stress) enhances memory only in
stressful-arousing conditions
- if yohimbine (NE stimulant) is given after training then memory is enhanced

Question 26

roozendaal (1999)

Answer 26

task 8 - amygdala and stress

Drug RU 29362 (GR agonist) injected in hippocampus after training
If NE is blocked in the amygdala then it does not modulate glu in hippocampus
If amygdala is not there, you can’t modulate memory – see next slide

Question 27

cahill and mcnaugh (1998)

Answer 27

task 8 - amygdala and stress

Experiment:
Condition 1. arousing movie clips
Condition 2. static movie clips
They look amygdala activity and 3 weeks later they give them a memory test – the
higher amygdalar activation was when watching the arousing movie clip the more
movie clips they were able to remember :D , for neutral /static material there is NO
EFFECT!

Question 28

van stegeren (2005)

Answer 28

task 8 - amygdala and stress

When humans are given a beta blocker (beta-adrenergic blocking agents) when
watching arousing material there is less activity in the amygdala (figure B) – showing
that NE plays a role in activating amygdala

Question 29

tas (2017)

Answer 29

task 5 - sushi belt model

• microtubules: Microtubules in a neuron are used to
  transport substances to different parts of the cell. For
  example, neurotransmitters are made in the cell body
  close to the nucleus, but need to travel long distances to
  the end of axons where they will be used for synaptic
  transmission.
• motor-paint technique developed to see how are the
  microtubules organized inside the dendrites, they’re
  interested in that because the microtubules transport
  the molecules travelling to the synapse . They look
  specifically at tyrosinated or acetylated microtubules
  (MT)
• microtubules are either end positive or end negative
  and the motors that travel in these microtubules they are
  specific for one direction, in dendrides molecules in MT go
  in both directions
• on the left the whiter the more calcium there is
• on the right – black ampa receptors, when you have a line
  that goes from left to right then it is going outward, from
  top to bottom they are inward (going towards the soma),
  pause/blue are not moving

Question 30

doyle (2011)

Answer 30

task 5 - sushi belt model

• things always travel within the dendrite and when the
  synapse needs something – takes it out of the pool what is
  available

Question 31

afner (2019)

Answer 31

task 5 - mRNA transmission

• where are proteins made in or around the synapse?
  You can study this by using metabolic labelling, one of the
  numerous ones is called puromycylation, puromycin is an
  antibiotic very small molecule. t RNA is the intermediate btw
  the ribosome and the amino acid which will at the end serve to
  make a protein. Puromycin is a aminoacyl t RNA analogue so it
  gets loaded at the place of the amino acid on all the t RNAs – in
  other words puromycin is transported by t RNA – when all t
  RNA is loaded with puromycin which is then transported to the
  ribosome and released to substitute an amino acid – this
  terminates the translation so you end up having truncated
  proteins (proteins that are not fully ready) but it carries
  puromycin that can be detected with an antibody – this way
  you can see in what location the proteins were being made
• figure: neuron expressing GFP in green and v GLUT1 in pink
  (excitatory terminals)
  Method used: expansion microscopy , when all the antibodies
  are ready you put them into a gel that expands when it’s in
  water so that cell becomes very big and this way we can see
  synapses very well
• red: detecting site of protein synthesis , there is a lot of
  activity outside the neuron of interest as a lot of cells are on –
  only a couple of neurons are expressing GFP (what interests us)
• red shows that we have a lot of protein synthesis in the
  dendrite, also inside the spine (in the middle and not in
  postsynaptic density) and also, unexpectedly, a bit of protein
  synthesis in the pre synaptic terminal – from these results we
  can say that protein synthesis is basically happening
  everywhere  65% in POST SYNAPSE of the spines produce
  proteins after only 5 minutes, if labelling would have been
  longer probably the percentage would have been higher, 37%
  in PRE SYNAPSE of the spines produce proteins
• so we induce plasticity on those neurons – protein
  synthesis – in presynapse, postsynapses and also INHIBITORY
  presynaptic TERMINALS (not mentioned above)
• expain and be able to read the table!

Question 32

afner (2015)

Answer 32

task 5 - surface diffusion

• how come the phosphorylation of this really remote RS
  protein has any impact? To investigate this they use
  FRET, you have two fluorophores, one that when is
  directly excited is going to shine some green
  fluorescence (GFP) – if you have another fluorophore in
  proximity then it could also excite that and if this
  happens the green disappears as it will excite another
  fluorophore that will shine red – there is an overlapping
  level of energy between the emission and excitation –
  when an electrode (green) is excited the lifetime of it is
  going to be reduced a lot as it is going to have multiple
  ways to escape from that high level of energy as
  electrodes when they’re in a high state they want to go
  down so they look at the half-life of green protons – the
  more green fluorophore interacts with red the more the
  half-life will go down
• in the dendrites it is more green and inside the spine
  there is red – in the red (spine) there is strong
  interaction between PDZ-95 and the receptor
  REVIEW SLIDE MIDDLE AND LOW PART- CAN’T
  UNDERSTAND FROM LECTURE
• why if you modify domain WT (blue circles) then a
  change in the receptor’s mobility happens?  charge in
  blue dots is positive , those positive charges bring the
  domain close to the membrane. If you put a negatively
  charged amino acid then it will bring it further from the
  membrane – when charge balance is changed then
  interaction PSD 95
• if there is a strong interaction between green and red
  fluorophore then there is WHAT THE FUCK DOES SHE
  SAY?
• in her research she does a mutation that mimics
  phosphorylation and it results ?
  CaMKII – phosphorylation mediated by it, it also stops
  the cargo, it recruits protein and cargos that enable
  protein synthesis (including the protein synthesis itself),
  it immobilizes directly the receptors within the
  transmembrane

Question 33

opazo (2011)

Answer 33

task 5 - surface diffusion

• AMPAR receptors are made of different
  proteins, one (RS) that is very important is one
  that binds to PDZ-95, which is the organizer of
  the postsynaptic density (reason why
  postsynaptic density looks so dark when looked
  in microscopy). RS protein has a domain that
  can be phosphorylated by CaMKII in 9 different
  sites
• if CaMKII gets activated and if you look at
  receptors that are diffusing
• in normal conditions you have a lot of mobile
  receptors and little immobile  if CaMKII is
  always active then receptors do not move
  anymore and they find a synapse thus caMKII
  should play a role in recruiting the receptors …
  but how does it do that?

Question 34

goldman-rakic

Answer 34

task 7 - delay period

Correlates: persistent activities during
the delay period

• In PFC: neurons are cue-selective, some are
  delay-selective and some are response-selective.

Oculomotor delayed response task in
macaque monkeys
❖Some neurons in prefrontal cortex were
active during the delay
❖These neurons were direction-tuned, i.e. a
correlated for spatial ‘working’ memory
❖This example ‘delay
neuron’ held on to
this piece of
information when
monkey looked at a
blank screen
❖She and colleagues
suggested that
similarly tuned
frontal neurons
formed a
recurrently
connected cluster—
similar to how visual
cortex works

Question 35

inagaki (2019)

Answer 35

task 7 - delay period

Mechanisms: persistent firing: within a neuron or
from a network?
If persistent activity is within a neuron, photoinhibition should turn it off.

If persistent activity is within a neuron, photoinhibition should turn it off.
Otherwise: a network mechanism
Premotor cortex in mice (activity predictive of correct/incorrect response)

Question 36

dotson (2018)

Answer 36

task 7 - persistent stimulus - selective activity

Networks? It could be local excitatory networks
(excitatory glu neurons giving excitation to each
other) or it could be mutual inhibition (excite local
network (group 1) but also interneuron which inhibits
more surrounding neurons (group 2) which are also
inhibiting, so inhibit inhibition leads to excitation
which then excite group 1. Plausible to think that
neurons are doing long-range synaptic interactions
across brain regions

• evidence of long-range synaptic interactions: stimulus selective activity during delay period. In vPFC + anterior and
  ventral Intraparietal sulcus (AIP/VIP) there is a lot of persistent firing in delay period but not in visual cortex

Question 37

masse (2020)

Answer 37

task 7 - attractor dynamic and sensorimotor transformation

• recurrent neural network – backward
  feedback , last layer gives feedback back to
  the input layer (A-B-A)
• in recurrent nn- display increasing persistent
  activity when the demand of the task
  increases

The alternative: hybrid attractor dynamic and short-
term synaptic plasticity model
Masse et al 2019 Nat Neuro
❖ The spiking induces
temporary (<1 s) changes
in synaptic weights,
perhaps via calcium
dynamics
❖ Such short-term synaptic
plasticity (STSP) could
keep the information till
the next burst of spikes!
❖ Orchestrated by beta and
gamma rhythm

Question 38

lundqvist (2018)

Answer 38

task 7 - gamma range oscillations

task/method:
experimental condition:
results:

Question 39

olafsdottir (2016)

Answer 39

task 3 - replay for memory consolidation

task/method: 
experimental condition: - co-recorded MEC and CA1 grid and
place cells to see whehter there was
coordinated replay (measured by
grid-place cell coherence) between
the two brain areas which you
would expect if replay is supporting
memory consolidation –this was
the case but coordination was
stronger for forward replay than for
reverse (graph gray and yellow)

results: hippo replay leads to coordinated grid cell replay in hippo’s principal cortical output region

• they also found that place cells
  were initiating the replay and the
  grid cells were behind 10 ms

Question 40

Alonso et al (2020)

Answer 40

task 6 -

- hippocampus separates all experiences by
time so it can differentiate them
- complementary learning system theory
 consolidation: hippo is a “fast”
learner and high plasticity and cortex
is a “slow” learner with low plasticity
– this allows extraction of
overlapping principles to an abstract
system after memory is encoded –
this memory will lose details and only
remember “gist” like info
- advantage of slow learner (pfc) is
that contrasting info (e.g penguin
after learning wings=flying) is stored
without erasing the other info

• Schema – great way to test semantic
  memory – large cortical network that creates
  long term memory only with one experience
  and it comes along with rapid systems
  consolidation (the longer you are in Nijmegen
  the better schema you’d have)
• in rodents there is a task to measure this,
  rat needs to get the same cue as it ate before
  (e.g. strawberry flavour)

Question 41

tse (2011)

Answer 41

task 6

• gene expression in the cortex – new pair
  associate has higher gene expression
• if limbic cortex is turned off (ampa receptor
  inhibitor) during encoding animals do not
  remember – gene expression in limbic cortex
  (= rat frontal cortex) is important otherwise
  they wouldn’t remember – if PFC is not
  active during updating of schema / semantic
  memory, then there is no rapid systems
  consolidation

Question 42

buzsaki 2013

Answer 42

task 6

• semantic memory in rodents is a under
  researched field
• semantic memory is “facts”. Episodic and
  semantic memories are both declarative.
• there is no rodent test that tests semantic
  memory 
• many contrasting ideas of what the hippo
  does
• Space: path integration and allocentric
  system (not egocentric) and episodic memory
  evolves from egocentric to allocentric view of
  the world (semantic)
• Episodic memory: hippo can be responsible
  for that, hippo is good at bringing everything
  together (H.M didn’t have episodic memory)
• index theory: hippo (the librarian) is a point
  where all the info are “put” together
• circuit researchers: hippo functions only as
  pattern completion (CA1) and pattern
  (DG)separation
• scene reconstruction: new theory – hippo is not very good for memory bc it has a fast turnover of synapses, instead
  the hippo does is completing the story that the cortex is telling – need hippo for reconstructing a scene and this
  would explain false memory formation (the hippo “fills” in missing info which are integrated from other memories)

Question 43

genzel (2019)

Answer 43

task 6

• semantic memories could come from
  episodic memories
• semantic memories formation – you have
  an experience (e.g. sitting in class) and some
  neurons activate. Recall  all the neurons
  that were active during memory formation
  are also active when recalling
• some neurons are more important than
  others (neuronal hubs) as if you inactivate
  those you lose the whole memory
• hippocampal hubs are especially important
  for episodic memories
• frontal cortex (human - pfc, mpfc, rodents -
  prelimbic and acc) hubs are important for
  storage
• default mode network is the “memory”
  network as it includes many memory hubs
• object space task is developed – based on principle of
  novelty, explore novel object inserted in space more – they
  do differently bc they overlap (5 trials spaced with breaks of
  45 minutes, they have different objects in each trial but
  same location – some locations have been presented less
  and they check whether the animal remembers by seeing if
  it explores more the item at the least presented location

Question 44

de quervain (1998)

Answer 44

SCHEMA FIG FROM THIS GUY - lecturer mentions a variety of experiments with him

Stress through glocorticoids impair retrival (see next slides) but enhances
consolidation

Train animal to be in platform,
Shortly before recall they stress animal – In control they recall training and stay more in platform, same for 2 minutes after
stressor or 4 hours after stressor. Significantly, we see that 30 min after stress they
can’t recall where the platform is as well as the other conditions – stress impairs
recall after 30 minutes as the cortisol response takes around 20-30 minutes to raise
plasma corticosterone levels

Glucorticoids impair memory recall!

Question 45

Monyer 1994

Answer 45

Task 4

Molecular basis of memory development: NMDARs
• GluN1 expression is already high at
birth and does not change across
development
• GluN2A is only expressed post-natally
and near-adult levels are reached by
~4weeks of age
• GluN2B expression is high at birth and
gradually goes down until ~4weeks of
age
• In the adult, GluN2A is the dominant
NMDAR subunit.
Monyer et al. (1994)

Question 46

Tang 1999

Answer 46

Task 4
Molecular basis of memory development: NMDARs
• Differences between GluN2A and GluN2B
• GluN2Bs have higher affinity for
glutamate
• GluN2As deactivate more quickly
• GluN2B synapses have a lower
threshold for LTP!
• Over-expression of GluN2B leads to
enhanced memory

Question 47

Travaglia 2016

Answer 47

Task 4

Molecular basis of memory development: NMDARs
• Training on a contextual fear conditioning task at
P17 (infantile amnesia period) accelerated the
switch in GluN2A/GluN2B expression
• Perhaps this molecular switch represents a critical
period for memory development?
Travaglia et al. (2016)

Question 48

Lohmann 2014

Answer 48

Task 4

Molecular basis of memory development: NMDARs
• Developmental changes in GluN2A and
GluN2B expression levels show that there
is a development ‘switch’ in which GluN2
subunit dominates NMDARs
• This switch occurs coincidentally with
the emergence of episodic memory
• What are the differences between GluN2A
and GluN2B?

Molecular basis of memory development
• Synaptic plasticity also involves altering
protein interactions in post-synaptic
cells via kinases
• A key kinase is CaMKII
• CaMKII is activated if calcium enters
the post-synaptic cell.
• Once activated it translocates to the
synapse and binds to GluN2Bs, inducing
spine growth.
• CaMKII-GluN2B interactions are vital
for LTP induction and activation of
CaMKII is sufficient to potentiate
synapses
• Interestingly, CaMKII levels reach near-
adult levels during 4th post-natal week
-The developmental period associated with the emergence of memory is marked by
dramatic changes in the molecular composition and processes within excitatory
neurons
• Based on the developmental timeline of various molecular candidates, memory
development may depend on the GluN2A/GluN2B switch and the expression of
CaMKII
Lohmann & Kessels (2014)