memory2_2011

memory2_2011 - Learning and Memory II Nov 18 2011 Ralph...

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Unformatted text preview: Learning and Memory II Nov. 18, 2011 Ralph Adolphs 1. Declarative Memory 2. Nondeclarative Memory 1 Time: Nov 21 (Mon). 4 pm - 5 pm Location: SSEL Lab. Baxter 5 (in the basement of Baxter) Payment: around $15 for about 45 min. Sign-up URL: https://www.ssel.caltech.edu/ssel/signup.html 2 Memory consists of multiple stages Memory consists of multiple types 3 4 Memory retention Observed STM Review R708 0 MTM ARM 1 2 3 LTM 4 Time (h) 5 24 Current Biology postulated to exist, based on theLTM assumption that the olfactory task Dopaminergic US rutabaga STM, MTM and ARM act additively to produce the ioral tasks. Hence, dunce CREB staufen crammer fasII observed memory retention curve. rlying biochemical amnesiac Nf1 ADF-1 pumilio Notch linotte Acquistion evidence for the MTM STM Key existence of MTM camenebula from the neural circuits latheo volado experiments on amnesiac mutants [15,25]. The first haviors as well. leonardo radish clue came simply from comparing the retention curves hows many of the PKC Cholinergic of normal flies and amnesiac mutants [8]. amnesiac cribed for PavlovARM CS mutant flies show near-normal memory retention uding acquisition, Current Biology immediately after a single training session and again dependence, temaround seven hours later. In between these time ation, conditioned points, memory retention in the mutants is appreciaeffects ([7–10]; M. 5 6 7 (Fig. 1, A and B). A similar transient increase of the training and the response to the foot shock hereaft H3K9, H3K14, roups were successfully ableandlearn this task, Old similar among groups (fig. S5B). Animals and tab Youngobserved in H4K5, to H4K8 acetylation werewere not subjected to fear conditioning but genes w was 16-month-old mice. less 6-month-old mice showed significantlyWhereas that reezingH4K5 acetylation was up-regulated 60 min after otherwise were treated identically served as con- such a behavior during the memory test, fear conditioning in both age groups, a significant trols. Notably, the gene expression profile was intrace - hich indicated H4K5 acetylation was already detect- nearly identical among 3- and 16-month-old con- Additi impaired associative learning increase of fig. S1A). Additional groups of mice were 16-month- trol mice (Fig. 2A and fig. S6). This is consistent old mi able 30 min after fear conditioning in trained old mice. These 16-month-old mice failed to with our finding that histone acetylation, HAT, plicate up-regulate and Cognitive Diseases, C and D). and HDAC activities are similar among those remode Laboratory for AgingH4K12 acetylation (Fig. 1,European These data were confirmed by immunohisto- groups (figs. S2 and S3). In 3-month-old mice, and ta euroscience Institute, Grisebach Str. 5, D-37077 Goettingen, 2 Max Delbrueck Center S4). Moreover, the lev- 2229 genes (1980 up-regulated versus 449 down- chain r ermany. chemical analysis (fig. for Molecular Medicine, els of total H4 did not change between groups regulated) were differentially expressed 1 hour the dif nstitute for Medical Systems Biology, Robert-Rössle-Strasse (fig. S4), which showed DNA Microarray Facility, 0, D-13125 Berlin-Buch, Germany. 3that memory impairment after fear conditioning as compared with the age- represe eorg August University, Humboldtallee 23, D-37073 Goettinen, Germany. 4Harvard Medical School, Genetics Department, 5 l 7 Ave Louis Pasteur, Boston, MA 02115, USA. Fasteris SA, H-1228 Plan-les-Ouates, Switzerland. Fig. 1. Impaired learning and memory in 16-mont , These authors contributed equally to this work. acetylation. (A) Representative immunoblot showing his Present address: Department of Psychiatry, Division of , olecular Psychiatry, University Goettingen, von Siebold to fear conditioning (FC). Control mice (c) were treated Quantification of (A). (C) Analysis similar to that descri tr. 7, D-37075 Goettingen, Germany. (D) Quantification of (C). (**P < 0.01, *P < 0.05 versus c To whom correspondence should be addressed. E-mail: indicate SEM. .[email protected] , , , , www.sciencemag.org SCIENCE VOL 328 7 MAY 2 Peleg et al. (2010), Science 328:753. 8 9 Types of declarative memory ·ȂSemantic memory –Neocortex (esp. temporal) ·ȂEpisodic memory –Hippocampus, frontal lobes, association  cortex ·ȂAutobiographical memory –Frontal lobes, association cortex ·ȂFlashbulb memories –Amygdala, association cortex 10 Declarative memory is highly dependent on the hippocampus at encoding, and during consolidation it becomes gradually less dependent on the hippocampus and more dependent on cortex. Episodic memory is more dependent on the hippocampus than semantic memory. Episodic memory may become re-coded as semantic memory over time. 11 Modulation of Declarative Memory: --repetition --recency --re-consolidation --salience: --attention --distinctiveness (von Restorff effect) --emotional arousal 12 Memories of Challenger Accident (Neisser & Harsch, 1992) 13 Description 1: “When I first heard about the explosion I was sitting in my freshman dorm room with my roommate and we were watching TV. It came on a news flash and we were both totally shocked. I was really upset and I went upstairs to talk to a friend of mine and then I called my parents.” Description 2: “ I was in my religion class and some people walked in and started talking about it. I didn’t know any details except that it had exploded & the school-teacher’s students had all been watching it which I thought was so sad. Then after class I went to my room and watched the TV program talking about it and I got all the details from that.” 14 Memory Performance The Function of Emotion within Space and Time Memory Performance Space Conference…Assembly…Massacre…Company Time 15 Organization of Memory Long-term memory Declarative (relational) Procedural Nondeclarative Priming/ Perceptual Classical Conditioning Nonassociative Learning Facts & Events Emotional Responses Medial  Temporal Lobe Diencephalon Striatum Cerebellum Motor Cortex Skeletal  Muscles Reflex Pathways Neocortex Amygdala Cerebellum 16 Associative vs. Non-Associative Learning • Non-associative Learning: – Learning with respect to a single stimulus • Associative Learning: – Learning about relationships • Between stimuli • Between a behavior and an outcome 17 Associative vs. Non-Associative Learning • Non-associative Learning: – Learning with respect to a single stimulus • habituation and sensitization • Associative Learning: – Learning about relationships • Between stimuli: Pavlovian conditioning • Between a behavior and an outcome: operant/ instrumental conditioning 18 • Types of associations: – S-S, S-R, S-O, R-O, S-(R-O), etc. • US = unconditioned stimulus • UR = unconditioned response – UR occurs to US independent of learning • CS = conditioned stimulus – Initially neutral • CR = conditioned response – CR occurs to CS because of learning 19 20 ACQUISITION
 UncondiKoned
SKmulus
 
(UCS)
 CondiKoned
sKmulus
 
(CS)
 UncondiKoned
Response
 
(UR)
 TIME
 TIME
 CondiKoned
Response
 
(CR)
 TIME
 21 Some Common Pavlovian Procedures 22 Reward learning Associating stimuli or actions with the value of outcomes Value can be dissociated from sensory properties 23 24 25 Fear conditioning 26 Pavlovian Fear Conditioning in humans It is dissociable from declarative memory Amygdala = fear conditioning Hippocampus = declarative memory 27 28 29 30 Phelps et al. 31 Phelps et al. 32 Phelps et al. 33 Most of what we learn is through observation from other people “Social/observational learning” 34 What can be learned? --”prepared stimuli” --the example of language acquisition --> There are innate/genetic constraints on WHAT classes of stimuli can be learned and on HOW we learn about them Learning mechanisms vary through development 35 36 Fig. 1. Examples of stimuli used in the FM and EE experiments. (A) Previously unknown target study phase trial in the FM experiment. (B) Recognition test trial in the FM experiments. (C ) Previously unknown target study phase trial in the EE experiment. (D) Recognition test trial in the EE experiment. “Fast mapping” binomial test) was not signi and even num (Mann–Whitn mance also w different from patients and patients retai performance as a group (P three patients 0.04 for A.D. chance (P = 0 the same item recognized o week and we probability). M significantly d 13%) (Mann even E.C.’s p significantly d tantly, a clos that, similar and controls o ones they rem performance tributable 37 to Fig. 3. Associative recognition performance on the FM (A) and EE (B) tasks of amnesic patients and healthy controls. The horizontal line represents chance performance. Error bars represent the SEM. Sharon et al. there have b more so of a visual obje the specifici retrieval (19 differed with presentation modality (bo retrieval). Su degree of fle declarative m We also h the flexibilit through FM memory—co who was ava the FM-acqu he had learn both healthy correct resp nition, sugg Sharon et al., PNAS (2011) 108:1146 38 ticoids in or? They as pups with the Younger an odor press an on, after udy from uestion6. n from a s mother ned and ronment. s already d to the rticoids, the odor. the odor, ot secrete dala, and n seen in the odor sed with , showed secreted, other is b More than 10 d old Exposure to shock-paired odor Mother present Mother present and glucocorticoids in amygdala Glucocorticoid secretion, amygdaloid activation No glucocorticoid secretion, no amygdaloid activation Amygdaloid activation Avoidance Attraction Avoidance givers even in the face of noxious stimuli, Barr et al.1 w rite, “attachment [by such an infant] to the caretaker has evolved to ensure that the infant forms a bond to that caregiver brain, as when it comes to metaphorical heart, love and hate are by no means opposites. 1. Barr, G. et al. Nat. Neurosci. 12, 1367–1369 (2009). 2. Sullivan, R., Landers, M., Yeaman, B. & Wilson, D. 39 nd of age, itioned r) r this t ids ent a Less than 10 d old Exposure to shock-paired odor , a, ups, on, ior. e t only ticoid- Infuse dopamine Infuse glucocorticoids and dopamine receptor blocker No amygdaloid activation ds the don’t ids in They pups th the unger odor Infuse glucocorticoids Increased dopaminergic tone and activity in the amygdala Amygdaloid activation No amygdaloid activation Attraction Avoidance Avoidance Attraction b More than 10 d old 40 Classical vs. Instrumental • Classical Conditioning, behavior of animal has no effect on occurrence of US • CS → US • Instrumental Conditioning, behavior of animal determines occurrence of US – S-(R-O) or S-R or R-O • CS → behavior/no behavior → US/no US 41 42 At least 2 kinds of instrumental learning: Habit learning (depends on basal ganglia) Goal-directed (depends on prefrontal cortex) With time and practice, goal-directed learning may become habit learning: more automatic, less flexible, harder to change (this is a little bit reminiscent of episodic memory converting to semantic memory with time) 43 Quick recap: Pavlovian fear conditioning: amygdala Context fear conditioning: amygdala + hippocampus Trace conditioning: hippocampus Declarative memory consolidation: hippocampus Declarative memory storage/recall: complex “Fast mapping”: ? Not hippocampal-dependent Instrumental learning: habitized: basal ganglia Instrumental learning: goal-directed: frontal cortex 44 Some learning only requires a single trial Taste aversion conditioning Conditioned social defeat 45 Acquisition (Training on Day 1) Initial defeat session(s) Resident Aggressor Experimental animal in resident aggressor’s home cage Expression (Testing on Day 2 and subsequently) Non-Aggressive Intruder Experimental animal in its own home cage 46 Conditioned defeat 47 48 Memory consolidation during sleep? 49 50 51 52 53 ...
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