Learning & Memory

1. Learning & Memory June 24, 2011

2. Review Quiz • Explain the neural processes (chemicals and structures) involved in sleep. • What is a circadian rhythm? • Name and describe one sleep disorder.

3. Coloring Diagrams

4. The Neuroscience of Memory http://www.sfn.org/skins/main/pdf/brainfacts/2008/brain_facts.pdf

5. A + B are active at the same time strong synapse weak synapse A B A B To put it another way: “Cells that fire together, wire together.” 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. From Lecture by Randy Hall, Emory University , 2007

6. Hebb & Long-Term Potentiation

7. 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)

8. 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

9. Control NMDA receptors AMPA receptors Potentiated 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 From Lecture by Randy Hall, Emory University , 2007

10. 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.

11. 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?

12. 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.

13. 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

14. Types of Memory & Localization

15. Semantic Episodic (Facts) (Events) Knowing Remembering LONG-TERM MEMORY IMPLICIT (Nondeclarative) EXPLICIT (Declarative) Procedural Memory Skills, habits Emotional Memory Priming Medial Temporal Cortex Striatum Cerebellum Hippocampus Neocortex Amygdala From Lecture by Jocelyne Bachevalier, Emory University , 2006

16. Dentate gyrus Unimodal & polymodal association areas (frontal, temporal, and parietal) Parahippocampal cortex Entorhinal cortex CA3 CA1 Perirhinal cortex Hippocampus Entorhinal cortex Parahippocampal gyrus Subiculum Perirhinal cortex Explicit memory: Specific subregions From Lecture by Jocelyne Bachevalier, Emory University , 2006

17. Who Was H.M.? http://www.pbs.org/wgbh/nova/body/how-memory-works.html

18. H.M.’s Hippocampus Case H.M. Control A B Hippocampus Uncus C D Parahippocampal gyrus Hippocampus From Lecture by Jocelyne Bachevalier, Emory University , 2006

19. The Case of H.M.

20. Mirror Tracing Experiment http://www.pbs.org/wgbh/nova/body/corkin-hm-memory.html

21. Memory Impairments

22. 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

23. 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 beta-amyloid protein between neurons. • Tangles are formation of tau protein that have accumulated inside of cells.

24. 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

25. Plaques and Tangles http://med.kuleuven.be/legtegg/AD.html

26. 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.

28. Other Factors Affecting Memory • Stress • Fatigue • Medical conditions or medications • Diet and exercise • Others…? http://www.nikonsmallworld.com/gallery/search/all/neurons/8

29. Recency Vs. Primacy Experiment

30. The Fallacy of Memory

31. Eyewitness Memory

33. The Neuroscience of Learning http://jcb.rupress.org/content/161/4/666.2

34. 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)

35. 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) 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! From Lecture by Randy Hall, Emory University , 2007

36. 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

37. 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?

38. 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.

39. 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

40. Brainstorming • Define an example of classical conditioning, and identify the US, UR, CS, and CR. http://www.improve-education.org/id44.html

41. 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

42. 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?

43. Hippocampal Learning • Different aspects or types of learning seem to occur in different hemispheres of the hippocampus. From Lecture by Jocelyne Bachevalier, Emory University , 2006

44. The Space Place Experiment

45. Learning Disorders & Mental Retardation http://www.brainandlearning.eu/

46. 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

47. Causes & Treatment of LD 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 • 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

48. Mental Retardation & Down Syndrome 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 • Defined by IQ score below 70 • About 1-3% of the general population • Higher incidence in males than females 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

49. Causes of Mental Retardation 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 • 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

50. Treatment of Mental Retardation 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 • 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