Learning & Memory
June 24, 2011
Review Quiz
1. Explain the neural processes (chemicals and structures) involved in sleep.
2. What is a circadian rhythm?
3. 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.
To put it another way: “Cells that fire together, wire together.”
A BA + B are activeat the same time
weak synapse
A Bstrong synapse
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)
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…
Associativity of LTP
From Lecture by Randy Hall, Emory University , 2007
What is Required for LTP?
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
Control
Potentiated
NMDA receptorsAMPA 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://www.scientificamerican.com/article.cfm?id=making-smart-mice
http://thebusinessglue.com/tag/doogie-howser/
Types of Memory & Localization
LONG-TERM MEMORY
Medial Temporal
Cortex
StriatumCerebellum
IMPLICIT(Nondeclarative
)
EXPLICIT(Declarative)
Semantic(Facts)
Knowing
Episodic(Events)
Remembering
Hippocampus
ProceduralMemory
Skills, habits
Priming EmotionalMemory
Neocortex Amygdala
From Lecture by Jocelyne Bachevalier, Emory University , 2006
Explicit memory: Specific subregions
Unimodal & polymodalassociation areas(frontal, temporal,
and parietal)
Parahippocampalcortex
Perirhinal cortex
Entorhinal cortex
Dentategyrus
CA3
CA1
Subiculum
Hippocampus
ParahippocampalgyrusPerirhinal cortex
Entorhinalcortex
From Lecture by Jocelyne Bachevalier, Emory University , 2006
Who Was H.M.?
http://www.pbs.org/wgbh/nova/body/how-memory-works.html
ControlCase H.M.
A B
C DUncus Hippocampus
Hippocampus Parahippocampalgyrus From Lecture by Jocelyne Bachevalier, Emory University , 2006
H.M.’s Hippocampus
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 tanglesPlaques are built-up deposits of beta-
amyloid protein between neurons.Tangles are formation of tau protein that
have accumulated inside of cells.
Plaques and Tangles
http://www.ahaf.org/alzheimers/about/understanding/plaques-and-tangles.html
http://www.medinik.com/mental-disorders/protein-alzheimer%E2%80%99s
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)
Alpha(8-14 Hz)
Theta(5-6 Hz)
Delta(1-4 Hz)
(arousal, alertness, anxiety)
(relaxation, meditation, pre-sleep)
(learning, novelty, REM sleep)
(deep sleep, unconsciousness)
From Lecture by Randy Hall, Emory University , 2007
LTP & Learning Continues
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.
AP5
Modified from http://www.euroimmun.com/index.php?id=35&L=1
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 70About 1-3% of the general population
Higher incidence in males than females
http://www.impactlab.com/2008/10/07/new-blood-tests-to-detect-downs-syndrome/
http://scrapetv.com/News/News%20Pages/Health/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 SkillsTo foster productivityTo foster independenceEducational and behavioral managementLiving and self-care skills via task analysisCommunication 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 MazeCan an animal learn to find a platform
hidden in the water based on visual cues around the room?
Radial Arm MazeCan 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 Trial 10
Packard and McGaugh, 1992, J. Neurosci., 9:1465
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 food-baited arms?
Videos: A Normal Mouse vs a Mouse with a Genetic Memory/Learning Deficit
Modified from http://www.scielo.cl/scielo.php?pid=S0716-97602003000200009&script=sci_arttext
Decreased time?
Human Tests
Delayed Matching-to-SampleWisconsin Card SortIQ Testing
Visual Recognition Delayed NonMatching-to-Sample Task
Trial 1
Trial 3
Trial 2
++
++
++
Visual DNMS task
50
60
70
80
90
100
10 sec 30 sec 60 sec 120 sec
Per
cen
t C
orre
ct
Delays
Mishkin, 1978, Nature, 273:297.
MT
C
Retrograde Amnesia
Zola-Morgan & Squire, 1990, Science, 250:288
50
55
60
65
70
75
80
85
90ControlsH lesions
Perc
en
t corr
ect
+
2 weeks
+
4 weeks
+
6 weeks
+
12 weeks
+
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://en.wikipedia.org/wiki/Hybrot
http://www.wired.com/medtech/health/multimedia/2006/08/71457?slide=1&slideView=4
http://discovermagazine.com/2006/nov/minibrains-dishes
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.htmlhttp://news.bbc.co.uk/2/hi/science/nature/3096973.stm