CHAPTER 12

1. CHAPTER 12 Learning and Memory Learning as the Storage of Memories Brain Changes in Learning Learning deficiencies and Disorders

2. Brain Changes in Learning • Over 50 years ago Donald Hebb (1940) stated what has become known as the Hebb rule: • If an axon of a presynaptic neuron is active while the postsynaptic neuron is firing, the synapse between them will be strengthened. • Note: Hebb made this statement in the absence of much knowledge regarding neural architecture or decent anatomical evidence!

3. Changes in the structure of the synapse during Learning • Long-term potentiation (LTP): • increase in synaptic strength following repeated high-frequency stimulation • Increase in dendritic growth • Changes in receptor sites in synapse • Long-term depression (LTD): • decrease in synaptic strength when an axon of a neuron is active while the postsynaptic neuron is not depolarized. • May result in decreased dendritic growth • Also changes in receptor sites in synapse

4. Spread of learning circuits • Associative long-term potentiation: • synapse is stimulated weakly while another synapse on the same postsynaptic neuron is being stimulated strongly; both are poteniated • Helps build generalization or secondary associations • Associative long-term depression • weakening of a synapse that is active when the postsynaptic neuron is not depolarized • is inactive when the postsynaptic neuron is depolarized. • LTP, LTD, associative LTP, and associative LTD can all be summed up in the expression, “Cells that fire together wire together.”

5. The graphs show excitatory postsynaptic potentials in response to a test stimulus before and after repeated stimulation. (a) 100-Hz stimulation produced long-term potentiation that was evident 25 minutes later. (b) 5-Hz stimulation produced long-term depression that blocked potentiation established earlier.

6. How does LTP and LTD happen? • In most locations the neurotransmitter involved in LTP is glutamate. • There are two types of glutamate receptors: • The AMPA receptor • The NMDA receptor

7. Brain Changes in Learning • During initial trials: • Glutamate activates AMPA receptors but not NMDA receptors, • NMDA receptors NOT activated because they are blocked by magnesium (Mg) ions. • During LTP induction: • activation of the AMPA receptors by the first few pulses of stimulation partially depolarizes the membrane • This dislodges the magnesium ions • Dislodging of magnesium ions allows NMDA receptors to begin being activated. • .

8. Brain Changes in Learning • Thus: critical NMDA receptor activated with repetition • This NMDA activation result = influx of sodium (Na+) and calcium (Ca+) ions. • Action of Ca+ ions allows release of Mg • Release of Mg ions and thus stimulation of NMDA receptor: • Influx of Na+ and Ca+ further depolarizes the neuron AND • Calcium activates CaMKII. • CaMKII: is an enzyme that is necessary for LTP; • acts as a binary switch to change the strength of a synapse. • Allows growth at the synapse of dendrite

9. (a) Initially, glutamate activates the AMPA receptors but not the NMDA receptors, (blocked by magnesium ions) (b) IF activation is strong enough to partially depolarize the postsynaptic membrane- magnesium ions are ejected. The NMDA receptor can then be activated, allowing sodium and calcium ions to enter.

10. Brain Changes in Learning • The final stage of LTP: • involves alteration of gene activity • and the synthesis of proteins. • Changes responsible for structural modifications in the dendrites • These changes produce longer-lasting increases in synaptic strength: • Neurons develop increased numbers of dendritic spines: • partially bridge the synaptic cleft • make the synapse more sensitive. • Later, additional AMPA receptors are transported from the dendrites into the spines.

12. Research suggests Long term potentiation • plays fundamental role in learning. • Decreasing number of NMDA receptors in mice results in: • reduced LTP in the hippocampus • impaired learning. • Learning improved by chemically increasing LTP • Humans may possess genes related to various proteins involved in LTP. • Also supports data suggesting that what “works” to remember: • repetition • massed trials • Or other similar practice/rehearsal strategies • Mastery learning: Practice makes perfect • Practice grows your brain!

13. Learning while we sleep?? • Hippocampus has ability to acquire learning “on the fly” • That is, while the event is in progress • Why would this be important? • In contrast, longer time needed for long-term storage of declarative memories in the cortex. • Hippocampus appears to transfers information to the cortex during times when the hippocampus is less occupied, • for example, during sleep • May be function of dreaming.

14. Brain Changes during sleep • Neurons in rat hippocampus and involved cortical areas repeat pattern of firing sequences that occurred during awake learning • Presumably: “offline” replay provides cortex opportunity to undergo long-term potentiation • Cortex requires more time to develop LTP, perhaps due to complexity: Takes time for changes in synapse; dendrites • Hippocampus = STM store; cortex is your hard drive

15. Learning as consolidation • Consolidation • process by which brain forms a more or less permanent physical representation of a memory. • Memory is formed via consolidation • We will explain this later (LTP processes) • Retrieval = process of accessing stored memories. • Hippocampal formation plays a lead role in consolidation, • damage to that area accounts for difficulty learning new material • No consolidation, no memory!

16. Three stages of memory • Formation of memory • Remember, “memory” is a process, not a “thing • Takes time to form permanent memory • Cognitive psychologists: 3 stages of memory • Sensory register memory: recognizing info as important • Short term memory: • Is short in duration- no more than 20 sec typically • Has limited capacity: 7+/-2 • Must engage in active effort to transfer to long term memory • Long Term memory: • Unlimited duration; Unlimited capacity • Why forgetting? Interference or tissue loss

18. Storage of Memories in brain • STM: hippocampus stores information temporarily in the hippocampal formation. • LTM: Over time, a more permanent memory is consolidated elsewhere in the brain. • Memories are not stored in a single area • But: memory also NOT distributed throughout the brain. • different memories are located in different cortical areas • Tend to be located according to where the information they are based on was processed.

19. Types of memory • Declarative memory • involves memories of facts, people, and events, which a person can verbalize, or declare. • variety of declarative memory subtypes: • episodic memory (events) • factual memory • autobiographical memory • spatial memory (the location of the individual and of objects in space). • Nondeclarative memory involves memories for behaviors. • Memories for procedural or skills learning: motor memory • emotional learning • stimulus-response conditioning.

20. Declarative vs. nondeclarative memory • Why distinguish? • have different origins in the brain. • Represent very different behaviors/functions • How know which area processes which type of memory? • Animal tests: can conduct lesions • Testing rats in the radial arm maze • Determine which brain areas were involved in learning tasks corresponding to non-declarative and declarative learning • Damage particular brain areas • Test/retest rats and examine change in performance.

21. Declarative vs. nondeclarative memory • Research Evidence supports importance of hippocampus • Rats with damage to both hippocampi could learn the simple conditioning task of going to any lighted arm for food. • When every arm was baited with food: • Rats would skip over “new” arms • repeatedly returned to arms where the food had already been eaten. • Rats with damage to the striatum • could remember which arms they had visited • could not learn to enter lighted arms.

22. Role of amygdala inStorage of Memories • Amygdala = significant role in nondeclarativeemotional learning. • Nonverbal learning • Procedural, spatial, visual • Particularly emotional learning • But also involved in some procedural (motor) learning • Amygdala strengthens declarative memories about emotional events: • increases activity in the hippocampus. • If electrically stimulate amygdala: activates the hippocampus, • enhances learning of a non-emotional task, such as a choice maze.

23. STM or working memory • Remember: Working memory: temporary “register” for information while it is being used. • Working memory: phone number you just looked up • holds information retrieved from long-term memory while it is integrated with other information • Or used in problem solving and decision making. • Is short in duration and capacity! • Like your working memory for files in computer • If you don’t save, it is gone

24. Working memory = prefrontal function • Prefrontal area = working memory’s central executive. • manages behavioral strategies and decision making; • coordinates activity in brain areas involved in perceptual and response functions in a task; and • directs the neural traffic in working memory. • Damage to prefrontal area • Increased impulsivity • Lack of control for emotions • Poor short term memory

25. Forgetting? Brain Changes in Learning • A memory must be both • stable to be useful • Malleable to be adaptable • Need to remember new information • But must also be able to forget irrelevant/worthless information • Several ways the brain accomplishes this: • Extinction • Forgetting

26. The Case of H.M. • At the age of 7, • HM was knocked down by a bicycle • unconscious for five minutes. • Three years later: minor seizures • First major seizure occurred on his 16th birthday. • As he got older: increased intensity/frequency of seizures • averaged 10 small seizures a day • one major seizure per week. • When he was 27: surgeon did bilateral removal of temporal lobes where the seizure activity was originating. • Familiar story of severe seizure disorders, except for the bilateral removal of temporal lobes- this was exceptional

27. Why is H.M. interesting? • HM’s intelligence was not impaired by the operation. • His IQ test performance even went up, • Why? probably because post surgery was no interference from seizures. • Although H.M. could recall past events, couldn’t learn new things: • can recall personal and public events and remember songs from his earlier life, • difficulty learning and retaining new information. • Only hold new information in memory for a short while • , if distracted loses memory • Memory dissipates within few minutes • Almost COMPLETE loss of STM

28. Types of amnesia • Anterogradeamnesia • an impairment in forming new memories • HM’s symptoms one of first documented cases • Retrograde amnesia • inability to remember events prior to impairment • Also found with HM’ • the surgery also caused considerable retrograde amnesia • Typically: etiology of amnesia unknown • H.M. unique because definitive cause of amnesia • Rare chance to look at how brain forms memories

29. Hippocampal formation and memory • HM’s surgery damaged or destroyed the hippocampal formation • Structures near by along with hippocampus form this formation, nearby structures • Amygdala also important in this circuit (remember emotions!) • Why important? • The hippocampus consists of several substructures • Each has different functions • Which area damaged = what kind of damage

30. Hippocampal CA1 • Hippocampal CA1: provides the primary output from the hippocampus to other brain areas. • Damage in that part of both hippocampi results = moderate anterograde amnesia • only minimal retrograde amnesia. • If the damage includes the rest of the hippocampus, anterograde amnesia is severe.

31. Forgetting? Brain Changes in Learning • Extinction • involves new learning • Like LTP, extinction requires activation of NMDA receptors; • blocking these receptors eliminates extinction. • Forgetting is a problem, but is also adaptive • Prevents saturation of synapses with information that is not used regularly • Eliminates information that not made connections with other stored memories • Thus importance of elaborative rehearsal. • A number of studies indicate: Any time memory is retrieved it must be reconsolidated: During that time the memory becomes vulnerable again to disruption. • Bottom line: • Use it or lose it • Use it and risk losing it!

32. Traumatic Brain injury and Memory • TBI is leading cause of death and disability in young adults • 200-300/100,000 young adults admitted to hospital with TBI each year • Most are males • Mortality peaks from 15-24 years of age • Risk peaks between 15 and 30 • 70% result of motor vehicle accident

33. TBI: Traumatic Brain injury and Memory • Memory deficits = most marked sequels in TBI • Often persist beyond period of immediate recovery • Most frequent site of injury: temporal and basal-frontal regions of cortex • Areas highly associated with memory • Memory deficits occur in 69-80% of individuals with TBI • 36% show severe deficits • 73% of those with severe TBI show long term deficits • Predictors: degree of severity (marked by duration of loss of consciousness) and duration of amnesia

34. TBI: Traumatic Brain injury and Memory • Memory involves 4 sequential, interrelated processes: • Paying attention • Encoding • Storage • Retrieval • Memory impairment in TBI may involve some or all of these processes • 25% of TBI patients show difficulty with encoding or storage • Often lasts for months or years • Milder cases show disruption in attention, retrieval or combo of both • Difficulty with new learning, retrieval of new information

35. Impact on daily life • Memory deficits • Impair daily functioning • Prevent return to work/school • Impact ability to engage in daily living skills (bathing, eating, carrying out daily chores) • Depression often co-existing condition • May be biologically related • May be result of awareness of disability and loss

36. Compensation strategies • Must compensate or bypass memory problems and use residual skills more effectively • Memory compensatory strategies include • Use of mnemonics and memory aids • Cognitive training and memory building • Self-awareness of limitations and feedback • Memory groups • External memory aids: • Alarms for taking medication • Electronic memory aids • Neuropage alphanumeric paging system: • Important events entered into computer • Phone system pages the individual with reminder • Issue of ecological validity: is this “normal”