Lecture 8

Question 1

Learning and memory: the problem and definition
We do not know the neural mechanism of a thought
However, we do know:

Answer 1

We do know: large destruction of the cerebral cortex does not prevent a person from heaving thoughts (but it reduces the degree of awareness)

Question 2

Guyton Medical Physiology: “A thought probably results from the momentary pattern of stimulation of many different parts of the nervous system at the same time, probably involving most importantly the cerebral cortex, the thalamus, the limbic system and the upper reticular formation of the brain stem”.

Therefore, the mechanism of memory must be equally as complex, as the CNS needs to recreate the same spatial and temporal pattern

Question 3

All learning processes are an expression of the CNS’ plasticity:

Answer 3

• ability to change/functionally remodeled in
  response to the demands
• Δexperience –> Δsynaptic and hence neuronal connections: fundamental to learning and memory

Question 4

Cognitive function is explainable by

Answer 4

cellular events that influence plasticity: eg long- term potentiation events

Question 5

Some of the basic neuronal processes that probably lead to the process of memory

Question 6

Memory is the ability to

Answer 6

to retain and recall information

Question 7

Learning:

Answer 7

acquisition of knowledge, demonstrated in a new behaviour, that was not part of the behavioural repertoire

Question 8

Enriching environmental conditions vs Impoverished environmental conditions:

Answer 8

changes in biochemical and histological patterns

Question 9

Enriching environmental conditions: results in

Answer 9

thicker and heavier cortex, higher nr of dendrite processes and dendrite spines, higher transmitter synthase rates, thicker postsynaptic membranes, larger neuronal soma and nuclei, higher nr and activity of glia cells

Question 10

Question 11

Classification of broad types of learning

Answer 11

• associative learning
• non-associative learning

Question 12

Associative learning:

Answer 12

Pavlov’s dogs-simultaneous presentation of food with the ring of a bell –> association–> bell-only –> salivation
(think of sour lemon juice on your tongue…)

Question 13

Non-associative learning

Answer 13

Habituation and Sensitization

Question 14

Short-term memory: transient changes in synaptic activity

Answer 14

Habituation
Sensitization

Question 15

Habituation:

Answer 15

decreased response to an irrelevant stimulus that is presented over and over (eg a sudden loud noise)

Question 16

Sensitization:

Answer 16

exposure to a certain stimulus (eg noxious or intense) causes an enhanced response upon subsequent exposure

Question 17

Short-term memory involves transient changes in synaptic activity
under normal conditions

Answer 17

Action potential arrives pre-synaptically –> voltage-gated Ca2+ channels open –> exocytosis of neurotransmitter –> receptor binding –> depolarization

Question 18

Ca2+ channel modification: the most common form in learning

Answer 18

Mechanism Habituation: Ca2+ channels do not open as readily (decreased open probability) –> decrease in neurotransmitter release –> reduction in postsynaptic potential –> decrease in behavioural response
= memory for habituation stored in form of Δ in Ca2+ channels
Lasts for hours
First learning mechanism in human infants

Question 19

Figure 5.17: Habituation and sensitization in Aplysia.
Researchers have shown that in the sea snail Aplysia (shown in the photo), two forms of short-term memory—habituation and sensitization—result from opposite changes in neurotransmitter release from the same presynaptic neuron, caused by different transient channel modifications.

Question 20

Enhanced Ca2+ entry in sensitization through presynaptic interaction

Answer 20

Mechanism Sensitization:
Enhanced Ca2+ entry –> increase in neurotransmitter release –> larger postsynaptic potential
However: enhances Ca2+ through presynaptic facilitation: serotonin release at interneuron –> triggering cAMP pathway –> blocking of K+ channels –>decrease in K+ efflux –> prolonged action potential –> increase in Ca2+ influx

Question 21

Increased use of a pathways:

Answer 21

long-term potentiation (LTP)

Question 22

long-term potentiation (LTP)

Answer 22

enhances ability of presynaptic neuron to excite postsynaptic neuron –> increased excitatory responsiveness (last for days or weeks –> consolidation from short term to long term memory)

Question 23

What is needed for long-term potentiation (LTP)

Answer 23

sufficient depolarization at an AMPA receptor to drive out Mg2+ at a neighboring NMDA receptor

Question 24

What results from a long-term potentiation (LTP)

Answer 24

Increase in AMPA receptor density AND increase in release of ligand glutamate
NMDA: N-Methyl-D-aspartate, AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

Question 25

Possible pathways for long-term potentiation.

Question 26

Memory

Answer 26

Storage of acquired knowledge for later recall

Question 27

Memory trace

Answer 27

Neural change responsible for retention or storage of knowledge

Question 28

Short-term memory

Answer 28

Lasts for seconds to hours

Question 29

Long-term memory

Answer 29

Retained for days to years

Question 30

Consolidation

Answer 30

Process of transferring and fixing short-term memory traces into long-term memory stores

Question 31

Working memory

Answer 31

Temporarily holds and interrelates various pieces of information relevant to a current mental task

Question 32

Question 33

Question 34

Question 35

is needed in the consolidation phase

Answer 35

Protein synthesis

Question 36

A disruption of protein synthesis during a training/learning disturbs

Answer 36

-consolidation and inhibits long term memory -Short term memory is not affected

Question 37

The content of a memory cannot be reduced to molecular mechanisms in a single cell or single synapse, but has always to be ascribed to neuronal networks or assemblies

Question 38

Question 39

Question 40

Alzheimer’s disease (AD)

Answer 40

Cortical neuronal degeneration especially of frontal, temporal and parietal lobe, least in occipital lobe 4-5% of >60 years are affected In 5 % a genetic contribution Responsible for more than 50% of dementias basic functions such as vision, hearing, somato-sensory and motor function remain intact Cognitive performance affected Usually a fast progressive disease development with major dementia within 4-5 years

Question 41

First signs of Alzheimers disease

Answer 41

headache, slightly depressed

Question 42

Early state of Alzheimers disease

Answer 42

- memory loss: own items placed --> forgotten location Speech becomes less precise, “filling words” are used more often Difficulty with calculations, reading, writing Not able to continue work Personality and mood remains not affected Memory of names for people and things is dysfunctional Orientation: can’t find way to car/office Failure to draw sketches of complex figures, eg a watch or a bicycle

Question 43

Second state of Alzheimer's disease

Answer 43

years after begin of disease: atrophy of frontal lobe, decreasing interest on environment, clothes, hygiene, small steps Repeat of words or phrases--> rhythmic repeat of syllables --> complete loss of language

Question 44

End state of Alzheimer's disease

Answer 44

bed, stiff, non-responsive, pneumonia, uro-sepsis

Question 45

Question 46

Question 47

AD-microscopic changes:

Answer 47

1. Presence of neurofibrillary tangles, appearing as aggregates within the cytoplasm of neurons; tangles are composed of insoluble, protein-rich paired helical filaments (PHFs) 2. Accumulations of PHF’s occur within the distal processes to form characteristic senile plaques 3. Plaques contain a central amyloid core composed of β-amyloid (care: the presence of plaques and/or tangles is not-by itself-specific for AD, but their increased nr is)

Question 48

Question 49

Protein aggregates and neurodegeneration

Answer 49

Failure of the cells protein quality control Protein degradative pathways: ubiquitin-proteasome system and autophagy machinerey Large aggregates of protein accummulate in affected cells Aggregates may adsorb other macromolecules to themcell death Aggregates released from dead cells accumulate in extracellular matrix Interference with cell function  neurotoxicity and neurodegeneration Alzheimer’s disease or Huntington disease are caused initially by such protein aggregates

Question 50