L20 - 22 - Learning and Memory

Question 1

Implicit memory (5)

Answer 1

Memories that are not consciously recalled

• Habituation (e.g. ticking clocks)
• Sensitization (something potentially dangerous, surprising happens – removing habituation)
• Classical conditioning (Pavlov’s dogs)
• Operant conditioning (Skinner – pairing behaviour with reward or punishment)
• Procedural (reflexive)

Question 2

Explicit memory/declarative memory? What is the short-term version?

Answer 2

Memory of facts that can be consciously recalled. If short term, called working memory – stores newly acquired info and retrieved memories (seconds to mins).

Question 3

What brain structure does working memory depend on?

Answer 3

Prefrontal cortex and lateral intraparietal cortex

Question 4

Subdivisions of working memory

Answer 4

1) Central executive – prefrontal cortex: controlled the whole thing
2) Phonological loop – language areas of auditory cortex: digits, numbers, words – holds 7 digits
3) Spatiotemporal sketchpad: - everywhere else where are you in space and the environment around you e.g. touch, smell, taste

Question 5

Subdivisions of explicit memory

Answer 5

1) Semantic – meaning of words, sights, sounds, etc
2) Episodic – what happened: social and temporal relationships between different semantic memories
* Both important for language

Question 6

Semantic dementia

Answer 6

A progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains. The most common presenting symptoms are in the verbal domain however (with loss of word meaning) and it is characterized as a primary progressive aphasia.

Question 7

What brain structure is required in explicit memory to transfer from working to long term explicit memory?

Answer 7

Hippocampal formation -> primarily stored in the neocortex once consolidated (often involves “reliving” originals stimulus)

Question 8

What do lesions in the hippocampus proper affect what type of memory? Paracampal region?

Answer 8

Episodic, semantic

Question 9

How does repetition affect memory?

Answer 9

Repetition alters strength of active synapses, laying down an activity pattern that can be recalled (Hebb’s theory)

Question 10

Where does neurogenesis occur and does it have a role in memories?

Answer 10

Neurogenesis in dentate gyrus of hippocampus has a role in some memories

Question 11

Does sleep affect memories? What type of sleep?

Answer 11

Frequently sleep is required – slow wave (slowly going to sleep) and REM sleep (deep sleep) implicated
*in males it takes 3 nights of sleep to consolidated into LT memory from working memory, faster in females

Question 12

Theoretical structure of memory – Hopfield network
Stored as strength of connections between neurons in a network
-individual neurons can participate in several memories
-Neurons that are active strengthen connections to other neurons that are active, where partial stimulus is also to recall activity of whole stimulus
-distributed, not depending on single neurons
-theory applies to all networks of neuron-like elements e.g. Artificial intelligence
-Usually located close to the region that responds to a specific modality

Answer 12

Theoretical structure of memory – Hopfield network
Stored as strength of connections between neurons in a network
-individual neurons can participate in several memories
-Neurons that are active strengthen connections to other neurons that are active, where partial stimulus is also to recall activity of whole stimulus
-distributed, not depending on single neurons
-theory applies to all networks of neuron-like elements e.g. Artificial intelligence
-Usually located close to the region that responds to a specific modality

Question 13

Where is hippocampus found? Role of Hippocampus?

Answer 13

Hippocampus - primitive cerebral cortex located medially in temporal lobe
–Active during consolidation of explicit memory
–Includes dentate gyrus, where adult neurogenesis occurs

Question 14

What happens when hippocampus is damaged? Does it affect implicit memories?

Answer 14

-Damage prevents formation of new long term explicit memories but does not disturb consolidated memories
–Implicit memories still form

Question 15

Role of neocortex

Answer 15

•Explicit memory is associative – neocortex stalls this info
•Recall of stored memory of an event activates parts of cortex active when event was experienced
–Event is partially relived
•During LT memory formation (takes days) continual interaction between neocortex and hippocampus

Question 16

What physiological mechanism does strengthening of synapses occur by? What about weakening?

Answer 16

Strength – LTP: long term potentiation

Weakening – LTD: long term depression

Question 17

Hebbian modification - LTP definition? LTD definition?

Answer 17

• LTP: Synapses strengthen when pre- and post-synaptic neurons are active at the same time
• LTD: Synapses weaken when activity in pre and post synaptic neurons where out of sync with each other

Question 18

If by themselves LTP and LTD will lead to superposition catastrophe - why?

Answer 18

Unless there are other mechanism to balance activity of system out – associative memories will associate with strong memories and force out weaker memories. Hence the only memory you have will be the smell of your mother’s nipple.
-Synaptic homeostasis balances this out

Question 19

LTP is synapse specific - what does this mean?

Answer 19

If you stimulate input 1 and strengthen synapses, when you stimulate input 2, you don’t get the same response

Question 20

Post-synaptic mechanism for LTP - what are the steps taken for this to occur?

Answer 20

1) Glutamate excites AMPA receptors and unblocks NMDA receptors
2) Ca2+ entering via NMDA receptors activates Ca2+-dependent kinases
3) Kinases phosphorylate AMPA receptors – insert AMPA receptors into postsynaptic membrane
4) Ca2+ can also enter via voltage-gated Ca2+-channels

Question 21

Calcium-calmodulin dependent protein kinase II (CaMKII) – where is it found? How many subunits? How does it work?

Answer 21

–Found in spine cytoplasm
–Associated in rings of 10 subunits
1) Ca2+-calmodulin activates/disinhibits kinase activity
2) CaMKII is target for phosphorylation by CaMKII
3) Phosphorylation makes CaMKII constitutively active until dephosphorylated by a phosphatase
4) Memory stored in number of CaMKII molecules within ring that are phosphorylated

Question 22

What’s limited with Phosphorylation, receptor sensitization, and increased receptor number for memory storage?

Answer 22

All time limited

Question 23

For long term memory, you need?

Answer 23

Protein synthesis

Question 24

One mechanism identified in invertebrates involves phosphorylation of?

Answer 24

CREB (cyclic AMP Response Element Binding protein), which regulates gene expression.
*Ca2+ activates Adenyl Cyclase activates PKA activates CREB

Question 25

NMDA receptors are not the only source of Ca2+ - what other sources are there?

Answer 25

•Back propagating dendritic action potentials can open voltage-dependent Ca channels
•Can also increase cytoplasmic Ca2+ via release from intracellular stores
e.g. the metabotropic glutamate receptor mGluR1 causes Ca2+ release from endoplasmic reticulum
•Timing of Ca2+ entry is the key

Question 26

T/F: Ca2+ entry via NMDA plus voltage-dependent channels greater than sum of separate routes of entry by themselves

Answer 26

True

Question 27

Back propagation of an action potential in a dendrite

Answer 27

•Back-propagating dendritic APs activate voltage-dependent Ca2+ channels
•Close association of back propagating APs and EPSPs lead to either LTP or LTD
–Depends on timing

Question 28

If AP precedes EPSP, _ is activated, total increase in intra Ca2+ is ___ and you get LT_

Answer 28

Ca2+ dependent phosphatase, small, LTD

Question 29

If AP follows EPSP, _ is activated, total increase in intra Ca2+ is ___ and you get LT_

Answer 29

CaM Kinase II, larger, LTP

Question 30

Ebbinghaus – the forgetting curve, R =e^-t/s

Answer 30

Ebbinghaus – the forgetting curve, R =e^-t/s

Question 31

Dead reckoning

Answer 31

Process of calculating one’s current position by using a previously determined position, or fix, and advancing that position based upon known or estimated speeds over elapsed time and course.

Question 32

Why were Lashley’s cortical lesions so ineffective at diminishing learned performance in tasks like conditioned reflexes and maze running?

Answer 32

His assumption was that it was cortical but its’s actually everywhere. Learning of simple tasks is sub-cortical, hence have to take out huge areas of cerebral cortex to diminish learned performance.

Question 33

Patient HM – had both medial temporal lobe hippocampus removed (1/4 hippocampus left over)

Answer 33

HM showed that hippocampus is essential for the consolidation of explicit episodic memory. Could learn new things (could do procedural tasks) but cannot form new long term memories.

Question 34

Loni Sue Johnson - what happened to her?

Answer 34

Viral encephalitis, pure hippocampal loss on both sides. She has both anterograde and retrograde memory loss

Question 35

Hippocampus is part of cerebral cortex (the bit at the extremities)

• 90%: 6 layer cortex
• 10% of brain at edges goes from 5 to 4 to 3 cell layers (from inside to outside)

Answer 35

Hippocampus is part of cerebral cortex (the bit at the extremities)

• 90%: 6 layer cortex
• 10% of brain at edges goes from 5 to 4 to 3 cell layers (from inside to outside)

Question 36

Place cells accidently discovered and was initially thought to be memory of location, later seen as present location encoding and part of a system of space-encoding neurons:

• Space, grid, boarder, head direction and speed cells
• Many, if not most hippocampal neurons are place sensitive

Answer 36

Place cells accidently discovered and was initially thought to be memory of location, later seen as present location encoding and part of a system of space-encoding neurons:

• Space, grid, boarder, head direction and speed cells
• Many, if not most hippocampal neurons are place sensitive

Question 37

Are place fields topographic?

Answer 37

No

Question 38

T/F: Hippocampal neurons that respond as place cells also response to sensory stimuli (touch, taste and time). So a place field is also what happens in a place.

Answer 38

T

Question 39

Is the map set or does it reform with the exploration of new environments?

Answer 39

Initial exp with a small sample space of place cells suggested a fixed hardwired (predetermined) space map, but more complete studies showed that many place fields take several minutes to settle, and this depended on the rat’s attention to, and exploration of, the new environment – only rats that ACTIVELY explored the new environment would re-map their place cells.

Exp reformates the spatial map. As some neurons re-map rapidly, it is suggested that there may be a set of skeletal templates that can be selected then further refined as the specific of new environment are encountered

Question 40

DRAG-85 stops

Answer 40

NMDA mediated LTP

Question 41

Knockout subunit of NMDA in specific regions affects place fields by?

Answer 41

Reducing their ability to stabilise place fields in new environment

Question 42

Blocking LTP didn’t abolish place cells, but it stopped them from doing what?

Answer 42

Stops them from adapting to new environments – basic map is okay but it doesn’t refine.

Question 43

How and why do new map features/locations get stabilized? What is the role of attention in learning?

Answer 43

Selective attention, not general arousal. Rats trained to navigate by odour showed good odour selectivity in hippocampal cells but not good spatial maps, even though they covered the same territory as rats who were trained to follow spatial cues (and had good spatial maps) – these rats selectively paid attention to the odour rather than the spatial maps.

Question 44

What rhythm is dominant during exploratory phase of navigation?

Answer 44

Neurons fire in accord with a 6 – 10 Hz (theta) rhythm – dominant

Question 45

Consolidation is due to the ____ ____ _____ that spreads as ripples through the hippocampus and its entorhinal connection during _____ and _____. The sharp-wave activity is optimal for LTP and spreads via entorhinal cortex to cerebral cortex – learning is transferred from the ____, becoming consolidated as ___ representations. May relate to conscious recall of spatial info. The sharp-wave ripples also seem to be imaginary or rehearsal – once a map is established we have access to mental travel time estimation.

Answer 45

Sharp wave activity, rest and sleep, Hippocampus, Cortical

Question 46

Where do the signals that contribute to the hippocampal place fields come from?

Answer 46

Despite predictions, place fields were not generated from intra-hippocampal connections – isolating CA1 from CA3 and DG didn’t have much effect. Instead it comes from the entorhinal cortex.

Question 47

Difference between place cells and grid cells

Answer 47

The entorhinal cortex showed strong modulation by place with clearly silent regions separating place fields. Unlike place cells (that fire when the rat is in a particular location) grid cells fire when a rat is in a multiple of a particular distance. Grid cells determine mapping on place cells.

Question 48

Grid cells form a ____ or ____ grid. They are ____ _____ but denser space ____ and wider ____. The mesh size varies from ___ to over __ (so wide earlier closely spaced neuronal recordings miss the grid).

Answer 48

Grid cells form a triangular or hexagonal grid. They are non-topographic but denser space dorsally and wider ventrally. The mesh size varies from about 30cm to over 3m (so wide earlier closely spaced neuronal recordings miss the grid).

Question 49

The sequential firing of cells representing smaller/larger cells and smaller/larger grids give the rat a reference system for its location in its environment.

Answer 49

Larger, larger

Question 50

Head direction cells

Answer 50

A second type of cell defining the animal’s place in the environment appears in regions downstream of the hippocampus (entorhinal cortex, subiculum). Cell fires when animal is facing in a particular direction in an environment (relative to environment, not compass!)

Question 51

How do grid cells encode a specific combination of place cell identities for each new environment?

Answer 51

Dorsally – small grids, Ventrally – larger grids
The way you combine the varying grid sizes will give you 1000s of unique space cell mappings. Imagine it is a combinational lock where each grid cell mapping have different combinations in different environments.

Question 52

Navigation requires a combination of:

Answer 52

a) Dead reckoning - self-referenced movement from a known location
b) The generation of landmark-based maps

It is thought that the formation of a detailed map relies on repeated experiences with self-referencing explorations, the same way as semantic memories may become context-independent with repetition of episodic memories concerning a semantic relationship.