Transcript June 24_Learning & Memory

Learning & Memory
June 24, 2011
Review Quiz
1.
2.
3.
Explain the neural processes
(chemicals and structures) involved in
sleep.
What is a circadian rhythm?
Name and describe one sleep disorder.
Coloring Diagrams
The Neuroscience of Memory
http://www.sfn.org/skins/main/pdf/brainfacts/2008/brain_facts.pdf
Hebb’s Postulate

If a synapse is active at approximately
the same time that the postsynaptic
neuron is active, then that synapse will
be strengthened.
weak synapse
A
B
A + B are active
at the same time
strong synapse
A
B
To put it another way: “Cells that fire together, wire together.”
From Lecture by Randy Hall, Emory University , 2007
Hebb & Long-Term Potentiation
LTP: The Beginnings

In the 1970’s Lomo &
Bliss studied two areas
of the hippocampus:



Perforant path:
connection between the
entorhinal cortex &
dentate gyrus of the
hippocampus
Dentate Gyrus: A
region of the
hippocampus
When Lomo & Bliss
applied electrical
stimulation to the
perforant path, they saw
a much higher response
in the dentate gyrus
(from Bliss & Lomo,
J. Physiol., 1973)
Associativity of LTP



Pairing a weak stimulation of
one set of inputs with a
concurrent strong stimulation of
another set of inputs can result
in LTP of both pathways
In other words, if one neuron is
stimulated weakly at the same
time a stronger stimulus is given
to a second neuron, BOTH
pathways will now have a
stronger response.
Sounds a lot like Hebb’s
Postulate to me…
From Lecture by Randy Hall, Emory University , 2007
What is Required for LTP?


Control

NMDA receptors
AMPA receptors

Potentiated
Ca2+
NMDA receptors, a
specialized type of
receptor that binds
glutamate
AMPA receptors, a
second type of
glutamatergic receptor
Calcium-activated
enzymes, such as
CaMKII & PKC and the
protease calpain, which
alter the activity of
NMDA & AMPA
receptors
From Lecture by Randy Hall, Emory University , 2007
LTP: Long-Term
LTP can cause changes in size and
shape of dendritic spines, allowing room
for more AMPA receptors to be
expressed.
 It may also cause changes in expression
of important genes, allowing for the
formation of more stable memories.

LTP and Memory
We know that LTP strengthens synapses
in the hippocampus so that cells that fire
together also wire together, according to
Hebb’s Postulate.
 But does this really apply to memory?

Yes! Roll Out The Evidence…
LTP is observed in the hippocampus and
cortex, regions that are known to be
involved in memory formation. It doesn’t
seem to be observed elsewhere.
 Like memory formation, LTP is quickly
performed and lasts for a very long time.
 Drugs or genetic manipulations that
enhance learning also enhance LTP.

Doogie Mice


For example, Doogie
mice have extra-high
levels (over-expression)
of the NMDA receptor
subunit NR2B in their
forebrains.
They show enhanced
LTP and also perform
exceptionally well on a
variety of memory tasks.
http://thebusinessglue.com/tag/doogie-howser/
http://www.scientificamerican.com/article.cfm?id=making-smart-mice
Types of Memory &
Localization
LONG-TERM MEMORY
IMPLICIT
(Nondeclarative)
EXPLICIT
(Declarative)
Semantic
(Facts)
Knowing
Episodic
(Events)
Remembering
Medial
Temporal
Cortex
Hippocampus
Procedural
Memory
Skills, habits
Priming
Emotional
Memory
Striatum
Cerebellum
Neocortex
Amygdala
From Lecture by Jocelyne Bachevalier, Emory University , 2006
Explicit memory: Specific subregions
Dentate
gyrus
Unimodal & polymodal
association areas
(frontal, temporal,
and parietal)
Parahippocampal
cortex
CA3
Entorhinal
cortex
CA1
Perirhinal cortex
Subiculum
Entorhinal
cortex
Perirhinal cortex
Hippocampus
Parahippocampal
gyrus
From Lecture by Jocelyne Bachevalier, Emory University , 2006
Who Was H.M.?
http://www.pbs.org/wgbh/nova/body
/how-memory-works.html
H.M.’s Hippocampus
Case H.M.
A
Control
B
Hippocampus
Uncus
C
D
Hippocampus
Parahippocampal
gyrus
From Lecture by Jocelyne Bachevalier, Emory University , 2006
The Case of H.M.
Normal Function
Memory Deficit
Mirror Tracing Experiment
http://www.pbs.org/wgbh/nova/body/corkin-hm-memory.html
Memory Impairments
Dementia
Mild cognitive impairment beyond what is
normal for the patient’s age, but not so
severe as to impact daily functioning
 May or may not progress to develop
Alzheimer’s
 Likely linked to degeneration of gray
matter in the brain

Alzheimer’s Disease
Severe memory impairments including
difficulty learning new information
 Associated with the formation of plaques
and tangles

Plaques are built-up deposits of betaamyloid protein between neurons.
 Tangles are formation of tau protein that
have accumulated inside of cells.

Plaques and Tangles
http://www.medinik.com/mental-disorders/protein-alzheimer%E2%80%99s
http://www.ahaf.org/alzheimers/about/understanding/plaques-and-tangles.html
Plaques and Tangles
http://med.kuleuven.be/legtegg/AD.html
Other Keys: APP



Amyloid Precursor Protein
Source of beta amyloid protein
How is this different in Alzheimers?



Enzymes like gamma-secretases cut APP into beta
amyloid pieces
These pieces of beta amyloid can then assemble
into plaques
Gamma-secretase activity on APP is
controlled by presenillin
 Genetic alterations in APP or presenillin can
lead to Alzheimer’s.
Other Factors Affecting Memory





Stress
Fatigue
Medical
conditions or
medications
Diet and exercise
Others…?
http://www.nikonsmallworld.com/gallery/search/all/neurons/8
Recency Vs. Primacy
Experiment
The Fallacy of Memory
Eyewitness Memory
The Neuroscience of Learning
http://jcb.rupress.org/content/161/4/666.2
Types of Learning

Perceptual: recognizing a particular stimulus
that has been perceived before
 Stimulus-response: Learning to perform a
behavior in the presence of a stimulus
 Motor: learning to make a new response (ie,
dancing, knitting, bike riding, etc)
 Relational: Learning about the relationships
between stimuli (ie, learning to associate a
cat’s meow with the softness of their fur)
LTP & Learning


Like Memory, LTP is heavily
involved in learning.
Brain rhythms that are optimal
for LTP induction are also
associated with learning.


A 5 Hz rhythm works best at
inducing LTP. This rhythm
consists of brief bursts of
stimulation separated by 200
msec.
5 Hz is a Theta rhythm that is
observed in the hippocampus
and cortex during learning
and REM sleep by EEG!
Beta
(15-30 Hz)
(arousal, alertness, anxiety)
Alpha
(8-14 Hz)
(relaxation, meditation, pre-sleep)
Theta
(5-6 Hz)
(learning, novelty, REM sleep)
Delta
(1-4 Hz)
(deep sleep, unconsciousness)
From Lecture by Randy Hall, Emory University , 2007
LTP & Learning Continues


AP5
Modified from http://www.euroimmun.com/index.php?id=35&L=1
Also, drugs or
manipulations that block
learning also block LTP.
Rats treated with an
NMDA receptor
antagonist (blocks
NMDA receptors) called
AP5 will have inhibited
hippocampal LTP and
deficits in learning.
Conditioning Learning
Classical conditioning: formation of an
association between two previously
unrelated stimuli to cause a reflexive
behavior
 Operant conditioning: similar to classical
conditioning, but involving a learned
(non-reflexive) behavior
 Can you think of any examples?

Classical Conditioning

Ivan Pavlov observed that dogs salivated
when presented with meat. This was an
unconditioned response (UR) because it did
not require training.


Thus, the meat is called an unconditioned stimulus
(US).
Pavlov paired the sound of a bell with the
presentation of meat. The bell is a conditioned
stimulus (CS); it does not cause a response
unless trained to do so when paired with the
US.
Pavlov’s Dogs

Now, Pavlov saw
that the bell (CS)
caused salivation
alone, even when
not in the presence
of the meat (US).

This means that the
bell now causes a
conditioned
response (CR).
http://animals.howstuffworks.com/pets/dog-training1.htm
Brainstorming

Define an example of classical
conditioning, and identify the US, UR,
CS, and CR.
http://www.improve-education.org/id44.html
Operant Conditioning

A hungry rat is put in an
operant chamber (“Skinner
box”). Will it press the
lever on the wall?



Probably not initially, but
eventually it will out of
boredom.
Once it presses the lever,
a food pellet is presented.
Yummy! This is a
reinforcing stimuli.
Will the rat now be more
likely to press the lever?

YES!
http://brembs.net/operant/skinnerbox.html
Skinner Boxes
What if pressing the lever causes an
unpleasant stimuli, like a footshock?
 This is called a punishing stimuli and will
decrease the likelihood that the rat will
press the lever.
 What are some examples of operant
conditioning, and punishing and
reinforcing stimuli in our lives?

Hippocampal Learning

Different aspects or types of learning
seem to occur in different hemispheres of
the hippocampus.
Left Hippocampus
Right Hippocampus
Tactile maze learning
-
+
Visual maze learning
-
+
Spatial position
-
+
Spatial memory
-
+
Recall of nonsense syllables
+
-
Recall of word lists
+
-
Paired associates
+
-
Self-ordered word recall
+
-
From Lecture by Jocelyne Bachevalier, Emory University , 2006
The Space Place Experiment
Learning Disorders & Mental
Retardation
http://www.brainandlearning.eu/
Learning Disorders (LD)

Academic problems in
reading, mathematics,
and writing


Performance
substantially below
expected levels
5-10% prevalence in the
United States

Highest in wealthier
regions of the United
States
Figure 14.2 Uneven distribution. The highest percentages of schoolchildren
diagnosed with learning disabilities are in the wealthiest states.
Abnormal Psychology: An Integrative Approach, 4th Edition, David H. Barlow Chapter 14: Developmental Disorders
Acknowledgements to Barbara L. Swarthout, Family & Consumer Sciences teacher at Elkhorn High School
Causes & Treatment of LD

Genetic and Neurobiological Contributions




Reading disorder runs in families
100% concordance rate for identical twins
Evidence for subtle forms of brain damage is
inconclusive
Requires Intense Educational Interventions


Remediation of basic processing problems
Improvement of cognitive skills
Abnormal Psychology: An Integrative Approach, 4th Edition, David H. Barlow Chapter 14: Developmental Disorders
Acknowledgements to Barbara L. Swarthout, Family & Consumer Sciences teacher at Elkhorn High School
Mental Retardation & Down Syndrome
Defined by IQ score below 70
 About 1-3% of the general population


Higher incidence in males than females
http://www.impactlab.com/2008/10/07/newblood-tests-to-detect-downs-syndrome/
http://scrapetv.com/News/News%20Pages/He
alth/images-2/Down-Syndrome-Child-3.jpg
Abnormal Psychology: An Integrative Approach, 4th Edition, David H. Barlow Chapter 14: Developmental Disorders
Acknowledgements to Barbara L. Swarthout, Family & Consumer Sciences teacher at Elkhorn High School
Causes of Mental Retardation

Most cases have no known cause, but there are
hundreds of known causes






Environmental – Deprivation, abuse
Prenatal – Exposure to disease or a drug / toxin
Perinatal – Difficulties during labor
Postnatal – Head injury
Genetic Components
Chromosomal Abnormalities


Down syndrome and Fragile X syndrome
Maternal Age and Risk of Having a Down’s Baby
Abnormal Psychology: An Integrative Approach, 4th Edition, David H. Barlow Chapter 14: Developmental Disorders
Acknowledgements to Barbara L. Swarthout, Family & Consumer Sciences teacher at Elkhorn High School
Treatment of Mental Retardation

Teach Needed Skills
To foster productivity
 To foster independence
 Educational and behavioral management
 Living and self-care skills via task analysis
 Communication training – Often most
challenging

Abnormal Psychology: An Integrative Approach, 4th Edition, David H. Barlow Chapter 14: Developmental Disorders
Acknowledgements to Barbara L. Swarthout, Family & Consumer Sciences teacher at Elkhorn High School
Class Debate: Cognitive
Enhancement
Learning about Learning
Animal Models
Test an animal’s ability to learn and
remember spatial information over time.
 Morris Water Maze



Can an animal learn to find a platform
hidden in the water based on visual cues
around the room?
Radial Arm Maze

Can an animal learn which arm contains a
reward when it is consistently placed in the
same arm of the maze?
Morris water maze
Trial 1
Packard and McGaugh, 1992, J. Neurosci., 9:1465
Trial 10
Radial Arm Maze



Will the rat learn and
remember which arm
has food and which
doesn’t?
Will he spend less time
in the empty arms of the
maze than in the foodbaited arms?
Videos: A Normal
Mouse vs a Mouse with
a Genetic
Memory/Learning
Deficit
Decreased
time?
Modified from http://www.scielo.cl/scielo.php?pid=S0716-97602003000200009&script=sci_arttext
Human Tests
Delayed Matching-to-Sample
 Wisconsin Card Sort
 IQ Testing

Visual Recognition
Delayed NonMatching-to-Sample Task
Trial 1
+
+
Trial 2
+
+
Trial 3
+
+
Visual DNMS task
Percent Correct
100
C
90
80
70
60
MT
50
Delays 10 sec
Mishkin, 1978, Nature, 273:297.
30 sec
60 sec
120 sec
Retrograde Amnesia
Percent correct
90
Controls
H lesions
85
80
75
70
65
60
55
50
2 weeks
4 weeks
+
+
6 weeks
12 weeks
+
Zola-Morgan & Squire, 1990, Science, 250:288
+
16 weeks
+
Wisconsin Card Sort



Participant must match
the new stimulus card to
the appropriate display
category.
No information about
matching criteria is
given, but participant is
told whether they are
right or wrong.
Rules are frequently
changed, and the time
taken to learn the new
rules reflects learning.
http://en.wikipedia.org/wiki/Wisconsin_card_sort
Intelligence Quotient Testing
http://en.wikipedia.org/wiki/Wechsler_Adult_Intelligence_Scale
Animats & Computer Technology

What is an Animat?
“A computer simulated or
robotic animal behaving in
an environment”
--Steve Potter, PhD
 Put another way: Neurons
can be used to control
robots and make them
behave in a particular way.

How to Create an Animat

Neurons from the cortex of a rat are removed
and grown on a surface covered in electrodes.
 These electrodes can both provide electrical
stimulation to the neurons and record electrical
signals from the neurons.
 The electrical signals from the neurons are
then connected to a computer and used to
influence the behavior of the animat.
 The computer can then also provide a
feedback response to the neurons about the
behavior of the animats by applying an
electrical stimulation through the electrode.
Animat Setup
Demarse, T. B., D. A. Wagenaar, et al. (2001). "The Neurally Controlled Animat: Biological Brains Acting with
Simulated Bodies." Autonomous robots 11(3): 305-310
Animats
http://www.wired.com/medtech/health/multimedia/2006/08/714
57?slide=1&slideView=4
http://discovermagazine.com/2006/nov/minibrains-dishes
http://en.wikipedia.org/wiki/Hybrot
Why Would We Make an Animat?

We can use
the animat to
study learning
and neural
plasticity.
 How?
Animats and Learning
Animats and Art
http://www.neuro.gatech.edu/groups/potter/MEART.html
http://news.bbc.co.uk/2/hi/science/nature/3096973.stm