Lecture 8 Flashcards
Learning and memory: the problem and definition
We do not know the neural mechanism of a thought
However, we do know:
We do know: large destruction of the cerebral cortex does not prevent a person from heaving thoughts (but it reduces the degree of awareness)
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
All learning processes are an expression of the CNS’ plasticity:
- ability to change/functionally remodeled in
response to the demands - Δexperience –> Δsynaptic and hence neuronal connections: fundamental to learning and memory
Cognitive function is explainable by
cellular events that influence plasticity: eg long- term potentiation events
Some of the basic neuronal processes that probably lead to the process of memory
Memory is the ability to
to retain and recall information
Learning:
acquisition of knowledge, demonstrated in a new behaviour, that was not part of the behavioural repertoire
Enriching environmental conditions vs Impoverished environmental conditions:
changes in biochemical and histological patterns
Enriching environmental conditions: results in
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
Classification of broad types of learning
- associative learning
- non-associative learning
Associative learning:
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…)
Non-associative learning
Habituation and Sensitization
Short-term memory: transient changes in synaptic activity
Habituation
Sensitization
Habituation:
decreased response to an irrelevant stimulus that is presented over and over (eg a sudden loud noise)
Sensitization:
exposure to a certain stimulus (eg noxious or intense) causes an enhanced response upon subsequent exposure
Short-term memory involves transient changes in synaptic activity
under normal conditions
Action potential arrives pre-synaptically –> voltage-gated Ca2+ channels open –> exocytosis of neurotransmitter –> receptor binding –> depolarization
Ca2+ channel modification: the most common form in learning
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
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.
Enhanced Ca2+ entry in sensitization through presynaptic interaction
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
Increased use of a pathways:
long-term potentiation (LTP)
long-term potentiation (LTP)
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)
What is needed for long-term potentiation (LTP)
sufficient depolarization at an AMPA receptor to drive out Mg2+ at a neighboring NMDA receptor
What results from a long-term potentiation (LTP)
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
Possible pathways for long-term potentiation.
Memory
Storage of acquired knowledge for later recall
Memory trace
Neural change responsible for retention or storage of knowledge
Short-term memory
Lasts for seconds to hours
Long-term memory
Retained for days to years
Consolidation
Process of transferring and fixing short-term memory traces into long-term memory stores
Working memory
Temporarily holds and interrelates various pieces of information relevant to a current mental task
is needed in the consolidation phase
Protein synthesis
A disruption of protein synthesis during a training/learning disturbs
-consolidation and inhibits long term memory
-Short term memory is not affected
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
Alzheimer’s disease (AD)
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
First signs of Alzheimers disease
headache, slightly depressed
Early state of Alzheimers disease
- 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
Second state of Alzheimer’s disease
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
End state of Alzheimer’s disease
bed, stiff, non-responsive, pneumonia, uro-sepsis
AD-microscopic changes:
- Presence of neurofibrillary tangles, appearing as aggregates within the cytoplasm of neurons; tangles are composed of insoluble, protein-rich paired helical filaments (PHFs)
- Accumulations of PHF’s occur within the distal processes to form characteristic senile plaques
- 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)
Protein aggregates and neurodegeneration
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 themcell 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
