Learning & Memory

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


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


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)


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



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



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



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



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

Learning & Memory

Documents

Transcript of Learning & Memory