Learning and Memory

Question 1

Two types of LTMs

Answer 1

Implicit and explicit

Question 2

Explicit

Answer 2

Conscious, intentional recollection: factual information, past experiences and concepts

Question 3

Divided into two parts (explicit):

Answer 3

Episodic (personal experiences) and semantic (factual information)

Question 4

What is the hippocampus most important for?

Answer 4

Explicit memory, particularly episodic memory (WWW)

Question 5

External events are represented in the brain by?

Answer 5

Spatiotemporal patterns of neural activity - must themselves be the agents of synaptic change

Question 6

Where must the location of storage, or ‘engram’ of learning and memory be found?

Answer 6

Amongst those synapses that support activity-dependent changes in efficacy

Question 7

Hebb’s postulate

Answer 7

Cells that fire together wire together

Question 8

Gordon Allport’s theory of cell assembly

Answer 8

If inputs cause same pattern repeatedly, set of active elements constituting that pattern become increasingly strongly interassociated

Question 9

What does this activity-dependent, positive-feedback process underlie?

Answer 9

Strengthening of effective synapses and facilitates the encoding of LTMs in the hippocampus

Question 10

Changes in synaptic efficacy first described?

Answer 10

Terje Lomo (1966) - persistent increase in synaptic strength - later characterised ‘long-lasting potentiation’ (Bliss and Lomo, 1973)

Question 11

What does LTP depend on?

Answer 11

NMDAR coincidence detector

Question 12

How is LTP primarily expressed?

Answer 12

Increased AMPAR conductance

Question 13

How can AMPAR conductance be increased?

Answer 13

Influx of Ca2+ through NMDAR activates CaMKII which either inserts synaptic AMPARs or phosphorylates existing

Question 14

Three distinct phases of LTP (ref)

Answer 14

LTP1 (2.1hrs), LTP2 (3.5 days) and LTP3 (20.3) - Abraham, 2003

Question 15

What did Flexner, Flexner and Stellar show in 1963?

Answer 15

Intracerebral puromycin led to memory loss of a learning task in mice

Question 16

In which environment do place cells set up their place fields rapidly?

Answer 16

Novel, remain indefinitely stable

Question 17

What happens if anisomycin is expressed the first time they are exposed to a novel environment? (ref)

Answer 17

When returned to the environment, place cell fields showed unstable firing patterns (Agnihotri et al., 2004)

Question 18

What does PSD-95 do?

Answer 18

Stabilises nascent spines, anchors receptors and scaffolding proteins to the membrane

Question 19

What proteins mediate spine enlargement via actin polymerisation?

Answer 19

Actin, CaMKII, Kalirin-7, Rac1

Question 20

Who showed that LTP induction is associated with dendritic spine formation in CA1?

Answer 20

Engert and Bonhoeffer, 1999

Question 21

What have several studies demonstrated (DA)?

Answer 21

Enhancement of LTP induction and LTM consolidation by dopamine

Question 22

What prevents a weak stimulus from producing LTP when exploring novel environments? (+ refs x 2)

Answer 22

D1/5 antagonist ONLY if present during exploration (Li et al., 2003; Frey et al., 1991)

Question 23

Chr2 expressed in what neurons?

Answer 23

Dopaminergic VTA in mice

Question 24

Difference in VTA neurons when exploring novel vs familar environments?

Answer 24

Significantly more burst firing

Question 25

What was the effect of optogenetic stimulation of VTA neurons?

Answer 25

No effect on rate of learning, but following completion of trials there was a clear improvement in the later recall of neural representations of space (McNamara et al., 2014)

Question 26

What do patients with MTL lesions show?

Answer 26

Retrograde amnesia that is temporally graded such that recent memory loss is greater than earlier memory loss

Question 27

What is retrograde memory loss restricted to? (ref)

Answer 27

Explicit memory, leaving implicit memory intact over time (Scoville and Milner, 1957)

Question 28

What do retrograde memory loss observations suggest? (ref)

Answer 28

MTL forms a temporary memory trace needed for explicit memories until they are consolidated to other brain areas, such as neocortex (Squire and Alvarez, 1995)

Question 29

What did Kim & Fanselow (1992) show?

Answer 29

Time-limited effect on the fear response of context-conditioned, but not tone-conditioned, animals

Question 30

[K&F] What was the effect of introducing a HPC lesion together with the CFC protocol?

Answer 30

Significant reduction in fear response

Question 31

[K&F] What was the effect of introducing a HPC lesion 28 days after the CFC protocol?

Answer 31

No difference between controls

Question 32

[K&F] What do they provide evidence for?

Answer 32

Storage reorganisation of LTMs to brain regions independent of the hippocampus

Question 33

What is the effect of CA1 fast optogenetic inhibition (even weeks after training)?

Answer 33

Blocks remote fear memory recall in CFC mice, which opposes SC model

Question 34

What happened when CA1 inhibition was extended to match the time course of pharmacological blockade?

Answer 34

Remote hippocampal dependence converted to hippocampal independence

Question 35

What did the inactivation of ACC lead to?

Answer 35

Prevented the recall of behaviours learned a month or more in the past

Question 36

What do Goshen's et al. (2011) observations suggest?

Answer 36

Memories consolidate to cerebral cortex, and while their retrieval is normally dependent on the hippocampus, it can adaptively shift to other brain regions

Question 37

What did Lui et al., (2012) identify, and how?

Answer 37

Small subset of DG neurons by exposing mice to a shock in context B which induced expression of ChR2/cFos

Question 38

What did optogenetic stimulation of DG neurons do in a neutral context?

Answer 38

Still drove freezing

Question 39

How did Ryan et al., (2015) extend this concept?

Answer 39

Also labelled input axons from EC

Question 40

What did Ryan et al. find?

Answer 40

Engram cells (DG neurons) had stronger connections from EC afferents, as well as higher spine densities, only if consolidated

Question 41

[Ryan] What did optogenetic stimulation of engram cells lead to?

Answer 41

Drove freezing even in the absence of consolidation - memory trace is always present but consolidation may link this to other neurons in the network

Question 42

What is memory reconsolidation?

Answer 42

Process of previously consolidated memories being recalled and actively consolidated

Question 43

What does the retrieval of LTMs cause?

Answer 43

Once consolidated, LTMs thought to be stable, but their retrieval of a memory trace can cause a labile phase that requires an active process to make the memory stable after retrieval is complete

Question 44

Who first showed the lability of memory?

Answer 44

Misanin et al. 1968 - ECT after brief presentation of conditioned stimulus led to memory loss

Question 45

What early studies treating OCD, delusions and depression were noteably successful? (ref)

Answer 45

Patients not anaesthetised and asked to focus on compulsions (Rubin, Fried & Franks, 1969)

Question 46

What is the effect of blocking protein synthesis in higher brain regions (e.g. amygdala)? (ref)

Answer 46

Prevents reconsolidation of memories, almost completely abolishing the fear response (Nader, Schafe & LeDoux, 2000)

Question 47

Labile phase of memory is a great candidate for targeted clinical interactions, for example:

Answer 47

Kroes et al., 2014: ECT in patients with unipolar depression disrupted reactivated, but not non-reactivated memories, for an emotional episode in a time-dependent manner