Learning and Memory

What structures are important for memory?

Hippocampus and mammillary body (found in temporal lobe)

Oscar is a 62 year-old man with a history of alcohol abuse was hospitalized with dehydration and malnutrition. Neurologic exams revealed nystagmus, along with a mildly ataxic gait. He did not know the date or name of the hospital. What condition does he have?

Wernicke-Korsakoff syndrome

Memories are ____, meaning that they are not static. They can be changed and/or influenced.

Dynamic

Are memories archived statically?

No. Memories are subject to constant change by various influences.

what is memory?

Memory is the ability to store information (a process). Specific information is stored in the brain.

what is recall?

Recall is reconstruction, in which memories are changed and distorted.

What is learning?

Learning is the process of acquiring new information.

State the stages of memory processing.

What are the four types of memory?

• Iconic Memory

• Short-Term Memory (STM)

• Intermediate-Term Memory

• Long-Term Memory

How long does Iconic Memory last?

Iconic Memories last an extremely brief amount of time, and are usually stuck in the sensory buffer.

How long does Short-Term Memory last?

about 30 seconds

How long does Intermediate-Term Memory last?

there’s not a set amount of time intermediate memories last. they outlive STM, but they’re not permanent.

ex: you’ll remember what you ate for dinner yesterday, but you’ll forget after a few weeks.

How long does Long-Term Memory last?

Long-Term Memories last for years.

What are the subtypes of Long-Term Memory?

declarative (explicit) episodic (specific personal experiences)and semantic memory (general knowledge)

non declarative (implicit) procedual (how to do certain tasks/skills) emotional conditioning

What is Retrograde Amnesia?

Retrograde Amnesia is loss of memories formed before the onset of amnesia (memory loss).

What is Anterograde Amnesia?

Anterograde Amnesia is inability to form memories after onset of amnesia.

Who is Patient H.M? What ended up happening to him?

• Patient H.M. had surgery to remove his amygdala, hippocampus, and temporal cortex on both sides

• He ended up with profound anterograde amnesia, but still had normal Short-Term Memory

• Patient H.M.’s memory deficit was only confined to verbal tasks.

Who was Patient N.A.? What part of his brain was damaged? What was his memory like?

• He had damage to his mediodorsal thalamus and mammillary bodies.

• Like H.M., he still has short-term memory, but he cannot form declarative long-term memory.

What is Wernicke-Korsakoff Syndrome?

Wernicke-Korsakoff Syndrome is a memory deficiency caused by a lack of Thiamine –I

What part of the brain is affected in Wernicke-Korsakoff Syndrome patients?

delete

How does Wernicke-Korsakoff Syndrome affect memory?

Wernicke-Korsakoff Syndrome causes confabulation – the patient uses made-up stories to fill in a gap in their memory and they believe it to be true.

What is damaged in Wernicke-Korsakoff Syndrome?

• orbitofrontal cortex

• mammillary bodies of the posterior hypothalamus

• basal frontal lobes

• generalized cerebral atrophy.

What part of K.C.’s brain was damaged?

K.C. had bilateral damage to his hippocampus

How was K.C.’s memory 20 years later?

K.C. had the ability to encode semantic memories (general facts)

However, he had no episodic memory, so he couldn’t recall any personal events.

True or False: The hippocampus stores long-term memory.

FALSE

What brain structure is involved in the consolidation of memory?

The Hippocampus.

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Where are most memories stored?

the cortex 

Does sleep enhance memory?

Sleep after learning ENHANCES memory processing the hippocampus, as it induces information transfer between hippocampus and medial prefrontal cortex (mPFC).

This transfer consolidates memories, so new memories become stable.

What types of events are remembered better?

Emotional events are remembered better

Are pleasant or unpleasant memories more easily remembered?

Pleasant emotions are usually remembered better than unpleasant ones

What is more important in memory: emotional arousal or importance of information?

It is emotional arousal that helps memory, not importance of information.

What is Post Traumatic Stress Disorder (PTSD)?

PTSD is unwanted recall of fearful stimuli that creates a feed-forward loop.

Each recall produces an emotional reaction that reinforces the traumatizing memory.

What is a possible treatment for PTSD?

Early treatment with propranolol, which is an adrenalin antagonist, may prevent emotional reinforcement of memories in PTSD.

What part of the brain is used to recall pictures?

The Right Prefrontal Cortex, and the Left AND Right Parahippocampal Cortex are activated.

What part of the brain is used to recall words?

The Left Prefrontal Cortex and the Left Parahippocampal cortex are activated.

Which part of the brain are Episodic Memories stored in?

Episodic memories are stored in the cortex, especially in the right frontal and temporal regions.

Encoding episodic memories involves the ____, while retrieving episodic memories involve the _____.

Anterior medial temporal system, Posterior medial temporal system

Non-declarative memory is involved with:

Sensorimotor skills, Perceptual skills, & Cognitive skills.

NOTE: All of these are impaired if you have basal ganglia injury

What are the following parts of the brain involved with?

• Hippocampus

hippocampus helps with NEW declarative memories (temporal and spatial memories)

What are the following parts of the brain involved with?

amygdala

amygdala helps the consolidation of emotions within memory

What are the following parts of the brain involved with?

infertotemporal cortex

the inferotermporal cortex retrieves visual images of memory

What are the following parts of the brain involved with?

prefrontal cortex 

prefrontal cortex is important in source memory (memory for the context in which something was learned/how did you learn it.)

What are the following parts of the brain involved with?

basal ganglia & cerebellum 

basal ganglia and cerebellum are important in skill learning for sensorimotor/motor patterns

What are the following parts of the brain involved with?

mediodorsal nucleus (thalamus)

the mediodorsal thalamus connects to prefrontal lobe, which integrates and sorts memories

Where can anatomical changes occur at a synapse to store memory?

changes occur at the presynaptic or postsynaptic neuron, or both at the same time. Proposed by Cajal.

What are the SPECIFIC anatomical changes at a synapse to store memory?

The presynaptic neuron can have an increase of neurotransmitter release

The postsynaptic neuron can have an increase in effectiveness of receptors

these events can happen simultaneously and exclusively.

What is the Don Hebb’s hypothesis?

There are two parts:

If the presynaptic axon AND postsynaptic neuron is active, synapses are strengthened (Neurons that fire together, wire together). Long-Term Potentiation

If presynaptic axon is active, but the postsynaptic neuron is inactive, the synapse is weakened. Long-Term Depression

• What are the cerebral changes of animals that are raised in enriched conditions?

• What are the behavioral changes?

• Cerebral Changes: Increased AChE activity, dendritic branching, and synaptic contacts

• Behavioral Changes: Better learning, aided recovery from malnutrition, & protection against age-related decline in memory

What is Long-Term Potentiation?

LTP is a persistent strengthening of synapses based on recent patterns of activity.

What is Tetanus?

Tetanus is a brief electrical stimulation that triggers thousands of axon potentials.

How does Tetanus affect Excitatory Post-Synaptic Potentials (EPSPs)?

After Tetanus, EPSPs remain high for hours.

List the steps of the use of AMPA and NMDA receptors in LTP in the hippocampus.

• Glutamate first activates AMPA receptors

• NMDA receptors don’t respond until enough AMPA receptors are stimulated to partly depolarize the neuron.

• NMDA receptors at rest have a magnesium ion block on their calcium channels.

• After partial depolarization, Mg²⁺ is removed and NMDA receptors allow Ca²⁺ to enter in response to glutamate.

• The large Ca²⁺ influx activates protein kinases as well as allows for the fusing of another vesicle to bring another AMPA receptor to the post-synaptic dendrite membrane.

• Now there are 2 AMPA receptors in the membrane, which unblocks more NMDA receptors.

• The activation of the protein kinases leads to the activation of CREB

• Activated CREB binds to DNA promoter regions

• CREB changes the transcription rates of genes, which produce proteins that change synapse structure and contribute to LTP

What receptors are upregulated as LTP begins, then are downregulated?

AMPA

After the activation of NMDA receptors, there is an upregulation of AMPA receptors. Does this upregulation last?

No. The AMPA upregulation is short-lived.

What is ICER?

ICER is Inducible cAMP Early Repressor which makes CREB antagonists compete with CREB for binding sites, disrupting the formation of long-term memories.

Induction of LTP activates what?

Induction of LTP activates a retrograde signal for presynaptic neuron to release more neurotransmitter. Nitric Oxide (NO) is an example.

How does LTP increase the effectiveness of synapses?

• Increasing postsynaptic receptors

• Increasing neurotransmitter release

How does a postsynaptic cell trigger long-term potentiation?

There’s a spike of action potential in the presynaptic cell a few milliseconds before the postsynaptic cell to trigger long-term potentiation.

What evidence is there that glial cells participate in learning and memory?

• Spatial memory is altered in mice with disrupted glial cells

• mice in enriched environments produce more glial cells

What evidence is there that glial cells participate in learning and memory?

DELETE

What types of glial cells are needed for LTP to develop?

Astrocytes are needed for LTP to develop.

• True/False: Memories of different durations use different neurochemicals

TRUE

Does memory strength change?

There are dips in memory strength after training, which is representative of transtitions between the stages of memory.

What happens when one stage of memory is blocked?

Blocking one stage of memory prevents formation of the next stage.

A 73 year old woman had a gradually worsening memory and had difficulty finding words. She knew her name, but couldn’t give her age, date of birth or even the current Presidents’ name. What was wrong with her?

The woman had Alzheimer’s Dementia.

What causes Alzheimer’s Dementia?

extracellular accumulation of beta-A4 amyloid (plaques) and intracellular accumulation of tau (neuro tangles)

What does Tau do in Alzheimer’s Dementia?

Normally, Tau stabilizes microtubules.

In Alzheimer’s Dementia, Tau causes microtubules collapse and form clumps to form neuro tangles.

Why is there an accumulation of extracellular amyloid in Alzheimer’s patients?

Accumulation of beta-amyloid is caused by a failure in Apolipoprotein (ApoE), which is supposed to break down beta-amyloid.

The accumulation of beta-amyloid incites inflammation that kills the cell

What are Prion Diseases?

Prion Diseases are diseases caused by native folded proteins becoming misfolded. This occurs when exogenous misfolded proteins infect an animal and convert native prion proteins into a misfolded form. Aggregation of Aβ leads to Prion diseases; this converts tau into toxic tau

Which memories remain stable as we age?

Which skills decline as we age?

Autobiographical and Semantic remain stable as we age

Executive function and navigation skills decline as we age

Why is brain mass decline a bad thing?

Shrinkage of the hippocampus correlates with memory impairment.

Describe hippocampal atrophy (shrinkage) in normal aging.

In normal aging, hippocampal atrophy reflects a change in volume, but there is no loss of neurons.

What are the possible ways to protect against age-related decline in memory and brain volume?

Having enriched experiences in life helps. These will result in:

• Reducing Cortisol allowing better response to short-term stress

• Prompting nerve growth factor expression in the hippocampus

• Enlarging neural networks that compensates for losses of synapses in aging

Are enriching experiences late in life too late to prevent age-related decline in memory and brain volume?

No. Active environments and cognitive activities reduce cognitive decline in aging.