Memory

Welke, Ph.D.
 Objectives
*Understand the difference between short and long-term memory
*Be able to describe the differences between declarative,
working and procedural memory
*Understand the four aspects of normal memory function
*Understand why sleep is important to memory
*Understand why the hippocampus is important to memory
formation
*Understand the basics of LTP (long term potentiation) and how it
is important to consolidation of information
*Why is the story of H.M. importantwhat type of memory loss
did he exhibit?
*Be familiar with the types of amnesia: retrograde, anterograde,
transient global amnesia, infantile, psychogenic
*Understand how Alzheimers disease, Korsakoffs Syndrome and
Wernickes Encephalopathy relates to memory
*Understand the memory functions related to the prefrontal
cortex
 Memory

Short-Term Long-Term

Working
Memory Declarative Non-Declarative

Episodic Semantic Procedural

 Long-Term: Declarative Memory
Facts - what, where, why
Two types of Declarative Memory:
1-Episodic Memory = memory of life events
2-Semantic Memory = memory of meanings &
understandings that do not involve memory of a
certain event

Virtually Unlimited Storage Capacity & Storage

Duration
Long-Term: Non-Declarative: Procedural Memory

how-to knowledgeskills and procedures

thought to involve simpler processes - acquisition requires

significant repetition

Driving a car, playing an instrument, learning to swim

Structures involved include the basal ganglia, cerebellum and

possibly the prefrontal lobe & amygdala

Most often affected with damage to subcortical structures

Huntington s chorea
Parkinson s disease
 Short-Term: Working Memory
Type of short-term memory

Limited in Capacity - 7 2 for nonsense numbers/

words

Limited in Storage Duration - Attention / Distraction

Operates in Problem Solving & Planning

Prefrontal cortex is important!

 Boat Apple

Blue Candy

Sail House

Water Frying Pan

Harbour Motorcycle
 Memory Mechanisms
Four aspects of normal memory function:
1-Encoding
-process of storing info / memories
2-Storage
-takes place in the cerebral cortex
3-Retrieval
-To recall a memory, we need cues to activate the
memory network and bring the stored information to
the conscious level
-Can be done with very limited cues
4-Forgetting
-this is normal
 How did you do?

Boat Apple

Blue Candy

Sail House

Water Frying Pan

Harbour Motorcycle
 Photographic (Eidectic) Memory
Most scientists do not believe that this
exists
People may have specialized ways of thinking
about the infonot any kind of enhanced
memory
Mnemonics & The Method of Loci
http://www.youtube.com/watch?
v=koAuqwMgVJw
http://www.youtube.com/watch?v=X-
xl7_hdWZo
 Dj Vu
The feeling that one has experienced a
situation or event beforean
overwhelming sense of familiarity
most likely is an anomaly of memory
Network overlap between short and
long term memorythe unconscious
mind (LT) perceives current situation
before conscious mind (ST) does
It is associated most commonly with
temporal lobe epileptics or seizures.
The synaptic firing is all off and there
is an incorrect perception of a memory
Many times associated with religious or
paranormal phenomenom
 Forgetting is normal!
Older memories are no longer able to be
recalled from storageusually a gradual
process
Forgetting occurs because
the event was never consolidated in
the first place
inability to retrieve memorythe
necessary cues are not there
interference from other memories
most likely new memories
Damage to the brain (i.e. Alzheimers,
aging)
You can cease forgetting byrepetition!
LTP!
 Memory and sleep
the role of sleep in the
formation of memories
is an area of very active
controversy
Procedural memory:
-improved/enhanced
with light sleep
Declarative/Episodic
memory:
-retained/consolidated
with deep sleep
Factors that DO impact learning & memory

Nutritional status
Level of stress
Temperature
Blood
oxygenation
Sufficient sleep
is essential for
optimal mental
performance
What structure/s is responsible for storing
information as memories?
-How does it do it?

http://www.morphonix.com/software/education/science/brain/game/specimens/hippocampus.html
Uncus

Parahippocampal
gyrus

Hippocampus
Hippocampus
Anatomy of Memory Consolidation
-Consolidation is the process of transition of a
short-term memory into a long-term memory

-Two groups of limbic system nuclei are required

for the formation of long-term memories
1) Medial Temporal Lobe Structures
Hippocampus
Entorhinal Cortex & Parahippocampal Gyrus
2) Diencephalon
Mammillary bodies
Medialdorsal nuclei and anterior thalamic nuclei
 Papez Circuit
Hippocampus

Fornix
Mammillary
Bodies
Mammillothalamic Tract
Entorhinal
Cortex
Anterior
Nucleus of the
Thalamus

Internal Capsule

Cingulate
Parahippocampal Cortex
Gyrus

To certain areas
of cortex to be
stored!
Anatomy of the Hippocampus

CA3

CA2
CA4

DG

CA1

Subiculum

EC

 Long Term Potentiation (LTP)
*A long lasting
enhancement of
synaptic transmission
resulting from high
frequency stimulation
of specific synapses

*Thought to be one of
the physiologic
underpinnings of
learning and memory
occurs at
glutamatergic
synapses in the
hippocampus

* Does strength of
experience = synaptic
strength??
 Long Term Potentiation (LTP)

*At rest, both receptors will bind glutamate, but the

NMDA receptor will be blocked by Mg++ and no current
will flow. *Mg++ removal allows Ca++ to enter the
postsynaptic neuron and this increase in
*The EPSP is then mediated by the AMPA channel.
Ca++ within the dendritic spines is the
*High frequency stimulation will cause summation of 2nd messenger trigger for LTP.
EPSPs, leading to a prolonged depolarization that expels
Mg++ from the NMDA channel
 Long Term Potentiation (LTP)
*Ca++ entering the cell will also activate
postsynaptic protein kinases. These
trigger a series of reactions that leads
to the insertion of new AMPA
receptors into the postsynaptic spine.
*This, then, increases the neurons
sensitivity to glutamate.

*LTP can also cause an increase in the

ability of the presynaptic neuron to
release glutamate.
*This requires a retrograde signal, in
the form of NO, to travel from the
postsynaptic to presynaptic neuron.
 Long Term Potentiation (LTP)
Long-Term Changes:
*Protein Kinases also
activate transcriptional
regulator CREB, which
causes expression in genes
that produce long lasting
changes in synaptic
structure.
___________________
Seconds to minutes =
ongoing electrical activity,
changes in different ions
& 2nd messenger systems
Minutes to hours =
protein phosphorylation &
covalent modifications
Hours to years = changes
in gene transcription &
translation resulting in
structural changes of
proteins & neurons
First Image of a Memory Being Made June 2009!

The increase in green fluorescence represents the imaging of protein synthesis at

synapses when memories are made

http://www.livescience.com/health/090626-memory-image.html
 NMDA receptors & Memory
-The density of receptors in the CA3 subfield is reduced
in aged individualsthey have not lost their memories
they just have trouble retrieving them
-The CA1 region is the most vulnerable to plaque
formation in the brains of Alzheimer's patients.
-Knowledge of how memory works at the molecular level,
could be important for drug development in the future
-Not only for Alzheimer's patients, but for all aged
individuals to recall memories and learned facts
Where are memories stored?
Stories of the
Little Seahorse

http://www.nytimes.com/2008/12/05/us/05hm.html?_r=2&hp
Control Patient H.M.
Anterograde / Retrograde Amnesia in H.M.

H.M.:
-Had no change in intellect or perceptual abilities
Could acquire new motor skills
Had mild retention of visual and tactual mazes

 Morris Water Maze

-assesses
spatial learning
& memory
Morris Water Maze
 Delayed Non-Match to Sample
(DNMS) Recognition Memory Task

Sample condition

Choice condition

Th

+

Delayed Non-Match to Sample (DNMS) - Recognition Memory Task
Lesions to Medial Temporal Lobe?

-Fornix Lesions ->

Minor Disruption of
Fornix
Memory Functions

-Bilateral Hippocampal
Lesions -> Major
Disruption of
Memory Functions

-Unilateral
Hippocampal lesions
-> produce little to
no impairment
 Amnesia

-Anterograde amnesia: the inability to form new

memories
bilateral medial temporal lobe damage
-Retrograde amnesia: a deficit in retrieving memories
prior to brain injury
generalized lesions
Infantile amnesia, psychogenic amnesia
 Alzheimer s Disease
-Neuronal degeneration of AD preferentially affects the
hippocampal formation, temporal cortex and basal forebrain
-Individuals typically have greater deficits in semantic aspects of
declarative memory compared to episodic declarative
memories
 Wernicke's Encephalopathy / Korsakoffs Syndrome
Wernickes Encephalopathy: Common in Alcoholics - the digestive
system of an alcoholic is unable to absorb vitamin B-1 (thiamine). This
deficiency affects the mamillary bodies, medialdorsal nucleus,
cerebellar vermis, CN III, IV, VI, VIII
-Results in: encephalopathy, opthalmoplegia & ataxia

Korsakoffs Syndrome: Prolonged deficiencies of thiamine can lead

to "Korsakoff's Syndrome". Patients have severe anterograde and
retrograde amnesia, disorientation and confabulation.
 Prefrontal Cortex
-last to develop, the new part of the brain, larger in humans and may relate
to intelligence, self-awareness, consciousness of perception & experience

Working Memory:
Type of short-term memory

Limited in capacity & storage duration

Executive Functions:
Operates in Problem Solving & Planning, goals, weighing different
outcomes, positive vs. negative

Motivation, decision-making, responsibility (?), social control, rule

learning, willpower

Interconnected with brain regions involved with emotion

(amygdala) arousal systems, attention

There may be reduced volume in individuals with psychological

disorders such as depression, sociopaths, schizophrenics, ADHD
 Phineus Gage: No
Longer Gage after his
incident in 1848
Delayed Recognition Span Task (DRST) - Working Memory Task
End!