memory1_2011 - Learning and Memory I Nov 16 2011 Ralph...

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Unformatted text preview: Learning and Memory I Nov. 16, 2011 Ralph Adolphs 1 Recap from last time Behavior is organized at many levels of control Reflexes Volitional action Motor control is distributed Action and perception interact Learning and Memory 2 Stages of Processing 1. 2. 3. 4. 5. 6. 7. Transduction Perception (early) Recognition (late perception) Memory (association) Judgment (valuation, preference) Planning (goal formation) Action 3 What is memory? What is remembering/ recollection? 4 “Life is that property of matter whereby it can remember. Matter which can remember is living; matter which cannot remember is dead. Life, then, is memory.” -Samuel Butler, Life and Habit (1910) In psychology, memory is an organism's ability to store, retain, and recall information and experiences - Wikipedia 5 Types of Memory - Plasticity, reorganization -processing changes - Nondeclarative memory -processing changes that lead to behavioral/ content changes - Declarative memory -processing changes that lead to content changes 6 6 How are changes encoded into the brain (a memory “trace” or “engram”)? How are memories stable in the face of a continuously changing brain? 7 7 Rat Whiskers are represented as “barrels” -ca. 4000 neurons per barrel -spontaneous: 1500 APs/ 200 ms -evoked: 4000 APs 8 9 10 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 11 12 13 14 15 15 16 16 Terms to Know • Encoding: learning new information • Consolidation: processes through which memory traces of newly formed information perseverate • Retrieval: recalling or recognizing previously learned information • Working Memory: online processing of information (shortterm memory) 17 Declarative Memory: --”immediate”, “iconic” --short-term, working memory: note that the neuropsychological definition is different from the cellular ca. 30-60 seconds, 7 “chunks” capacity, can think about it and use flexibly (hence “working” memory). --long-term: neuropsychologically, anything >60seconds, beyond the range of working memory. Nearly unbounded capacity, must retrieve into working memory to use. 18 How is memory related to conscious experience? Iconic Memory Working Memory LTM 19 19 • • • Iconic memory: very short (1s) sensory memory Working memory: 30-40s declarative memory. At least 2 processes have been studied: visuospatial scratchpad and phonological loop. Long-term memory: anything longer than working memory. • NOTE: short-term and long-term also refer to stages of memory consolidation at the molecular level. • • Remembering: awareness of the learning of an item Knowing: awareness of the familiarity of the item • • Recognition: retrieval triggered by the stimulus that is recognized Recall: retrieval triggered spontaneously or by an unrelated cue 20 “Short” and “Long”-term usage is inconsistent across disciplines. Neuropsychologically: short <60 sec, long > 60 sec Some psychology/clinical use: short is days/weeks, long is months, years (not a good usage). Better: Recent memory Remote memory 21 Cellular neurobiology: short is independent of gene transcription long depends on gene transcription, ultrastructural changes. Short is ephemeral, long is more permanent. 22 What brain regions subserve memory? Things that compromise memory: --Alzheimer’s disease --Normal aging --Encephalitis/anoxia --chronic alcoholism --benzodiazepines, scopolamine 23 Brain systems involved in declarative memory: Medial temporal lobe Association cortices Sensory cortices Basal forebrain Anterior thalamus Prefrontal cortex Mammillary bodies 24 25 MTL Amnesia: --complete anterograde --graded retrograde 26 26 Functional anatomy of amnesia Normal Brain from Corkin, 2002 Nature Rev. Neurosci. 3: 153-160 27 Patient H.M. (post-mortem brain ready to be sliced at UCSD) 28 28 The medial temporal lobe (MTL) and  declarative memory -Prior to 1953, the role of the MTL in memory was  relatively unknown -H.M. changed all that: bilateral temporal lobectomy =  complete anterograde amnesia    29 H.M.’s retrograde amnesia -Famous Faces  performance is normal  for 40s, then below  normal for 50s, then  severely impaired in  the 60s & 70s 70.0 % Correct -H.M.s RA extends  back ~11 years presurgery  Comparison 52.5 35.0 17.5 H.M. 0 1940s 1950s 1960s 1970s Famous Faces Recognition by Decade 30 Intact domains of memory in amnesia -Working memory: HM’s  digit span is normal -Skill and Perceptual  learning 31 Perceptual Learning Gollins partial pictures  test 32 Figure 1 (Left) A schematic view of the medial temporal lobe structures important for declarative memory. S, subicular complex; DG, dentate gyrus; CA1, CA3, the CA fields of the hippocampus. (Right) Lateral view of the rat brain (A) and ventral views of the monkey (B) and human (C) brain showing the borders of perirhinal cortex (gray), entorhinal cortex (diagonal stripes), and parahippocampal cortex (mottled shading). In the rat, the parahippocampal cortex is termed postrhinal cortex. (Adapted from Burwell et al. 1996.) 33 34 Gating of NMDA receptors NMDA receptors are “coincidence-detectors”. Their channel opens only when two events happen concurrently: 1. Binding of glutamate (in presence of glycine) Modified from Zigmond et al. (Eds.) Fundamental Neuroscience, Sinauer (1999) 3. NMDA receptors are very permeable to Ca2+. 2. Strong depolarization of the postsynaptic membrane (as by a back-propagating action potential). The depolarization relieves block of the Channel by Mg2+. 35 36 37 38 (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] , , , , SCIENCE VOL 328 7 MAY 2 39 Peleg et al. (2010), Science 328:753. 39 Testing Declarative Memory in Animals 40 40 41 The Morris Water Maze 42 42 43 43 44 45 46 47 48 ...
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