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Lecture11_Fortin_1slidepp - HIPPOCAMPUS II - MEMORY...

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Unformatted text preview: HIPPOCAMPUS II - MEMORY PROCESSES WHAT DOES THE HIPPOCAMPUS DO? Good question... N112A: Neuroscience Fundamentals November 2, 2011 OVERVIEW ❖ Why use animals to investigate the role of the hippocampus in learning and memory? ❖ The hippocampus and spatial learning/memory ❖ The hippocampus as a cognitive map ❖ Problems with that theory ❖ The hippocampus and non-spatial learning/memory ❖ So what does the hippocampus do? WHY USE ANIMALS TO INVESTIGATE THE ROLE OF THE HIPPOCAMPUS IN MEMORY? Limitations of memory experiments performed in humans Variability in extent of neurological damage Variability in subjects’ learning history Low spatial and temporal resolution of techniques Advantages of animal models Control extent and timing of brain damage Control information learned before and after brain damage Can use high-precision techniques that are not available in humans WHY USE ANIMALS TO INVESTIGATE THE ROLE OF THE HIPPOCAMPUS IN MEMORY? The brain is very similar across mammalian species, especially the hippocampus Human brain scan Detailed histology of Hippocampus and Medial Temporal Lobes (MTL) Human Rat Chimpanzee WHY USE ANIMALS TO INVESTIGATE THE ROLE OF THE HIPPOCAMPUS IN MEMORY? The brain is very similar across mammalian species, especially the hippocampus Human brain scan Various mammals from Manns & Eichenbaum, 2006 WHY USE ANIMALS TO INVESTIGATE THE ROLE OF THE HIPPOCAMPUS IN MEMORY? Similar pattern of connections between brain structures across mammals OVERVIEW ❖ Why use animals to investigate the role of the hippocampus in learning and memory? ❖ The hippocampus and spatial learning/memory ❖ The hippocampus as a cognitive map ❖ Problems with that theory ❖ The hippocampus and non-spatial learning/memory ❖ So what does the hippocampus do? THE HIPPOCAMPUS AND SPATIAL MEMORY WHY MAZES? Mazes were thought to be an good way to test learning and memory in rats (they live in burrows, use tunnels and paths) a b Figure 2. Complex maze learning (Small, 1901). a, picture of the Hampton Court Palace maze outside London, which served as inspiration (from Google Maps). b, Diagram of one of the maze used by Small (1901). from Fortin, 2008 THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) Theory: The hippocampus builds a faithful map of the environment Experimental evidence: Damage to the hippocampus impairs many spatial tasks “Place cells” in the hippocampus Larger hippocampi in people with advanced navigational capabilities THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) Damage to the hippocampus impairs performance in radial-arm maze in rats a b Radial-arm maze performance Arm baited with food X Arm previously visited X X Figure 4. Radial-arm maze task. a, The maze consists of 8 arms radially extending from a central platform. Before each session, all arms were baited with a food reward and optimal foraging performance would consist of running down the end of each arm only once (Olton and Samuelson, 1976). b, Animals with hippocampal damage were severely impaired in learning the task compared to control groups (McDonald and White, 1993). from Fortin, 2008 THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) Performance of a control animal in the radial-arm maze THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) Performance of a transgenic animal in the radial-arm maze THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) Damage to the hippocampus impairs performance in watermaze in rats a c b Figure 5. Morris watermaze task (Morris, 1981). a, Example swim path of a control rat. b, Example swim path of a rat with damage to the hippocampus. c, Top, performance of rats with hippocampal lesions (filled circles and lines), cortical lesions (filled circle and dashed lines) and normal controls (open circle) in acquiring the watermaze task. Place navigation refers to the condition in which the platform is hidden under the surface, cue navigation refers to a control condition in which the platform is visible to the animals. Bottom, swim path of a control subject on the transfer test in which the platform has been removed, showing a preference for the quadrant where the platform was located, and swim times of the rats in the four different quadrants (Morris et al., 1982). from Fortin, 2008 THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) A mouse learning the watermaze THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) “Place cells” in the hippocampus Cells firing at high rate when rat is in a specific location in the environment Original report: O’Keefe and Dostrovsky, 1971 THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) “Place cells” in the hippocampus Cells firing at high rate when rat is in a specific location in the environment Firing&rate:& Red&>&yellow&>&green&>&blue& Top view of square environment from O’Keefe and Burgess, 1996 THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) Latest technology: ~ 96-128 electrodes in the hippocampus Recording from > 40 place cells at once THE HIPPOCAMPUS AND SPATIAL MEMORY THE HIPPOCAMPUS AS A COGNITIVE MAP (O’KEEFE & NADEL, 1978) People with advanced navigational capabilities may have larger hippocampi Navigation-related structural change in the hippocampi of taxi drivers Eleanor A. Maguire*†, David G. Gadian‡, Ingrid S. Johnsrude†, Catriona D. Good†, John Ashburner†, Richard S. J. Frackowiak†, and Christopher D. Frith† †Wellcome Department of Cognitive Neurology, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom; and ‡Radiology and Physics Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom Communicated by Brenda Milner, McGill University, Montreal, Canada, January 28, 2000 (received for review November 10, 1999) Structural MRIs of the brains of humans with extensive navigation experience, licensed London taxi drivers, were analyzed and compared with those of control subjects who did not drive taxis. The posterior hippocampi of taxi drivers were significantly larger relative to those of control subjects. A more anterior hippocampal region was larger in control subjects than in taxi drivers. Hippocampal volume correlated with the amount of time spent as a taxi driver (positively in the posterior and negatively in the anterior hippocampus). These data are in accordance with the idea that the posterior hippocampus stores a spatial representation of the environment and can expand regionally to accommodate elaboration of this representation in people with a high dependence on navigational skills. It seems that there is a capacity for local plastic change in the structure of the healthy adult human brain in response to environmental demands. O ne important role of the hippocampus is to facilitate spatial memory in the form of navigation (1). Increased hippocampal volume relative to brain and body size has been reported in small mammals and birds who engage in behavior requiring spatial memory, such as food storing (2). In some species, hippocampal volumes enlarge specifically during seasons when demand for spatial ability is greatest (2, 3). In the healthy human, a priori regions of interest. The data were also analyzed by using a second and completely independent pixel-counting technique within the hippocampus proper. Comparisons were made between the brain scans of taxi drivers, who had all acquired a significant amount of large-scale spatial information (as evidenced by passing the licensing examinations), and those of a comparable group of control subjects who lacked such extensive navigation exposure. Methods Subjects. Right-handed male licensed London taxi drivers (n 16; mean age 44 years; range 32–62 years) participated. All had been licensed London taxi drivers for more than 1.5 years (mean time as taxi driver 14.3 years; range 1.5–42 years). The average time spent training to be a taxi driver before passing the licensing tests fully (i.e., time on The Knowledge) was 2 years (range 10 months to 3.5 years; some trained continuously, some part time). All of the taxi drivers had healthy general medical, neurological, and psychiatric profiles. The scans of control subjects were selected from the structural MRI scan database at the same unit where the taxi drivers were scanned. Those subjects below 32 and above 62 years of age were excluded as were females, left-handed males, and those with any health OVERVIEW ❖ Why use animals to investigate the role of the hippocampus in learning and memory? ❖ The hippocampus and spatial learning/memory ❖ The hippocampus as a cognitive map ❖ Problems with that theory ❖ The hippocampus and non-spatial learning/memory ❖ So what does the hippocampus do? REPORTS THE HIPPOCAMPUS AND SPATIAL MEMORY bath solution, which were amp 500 amplifier (Axon y, CA) interfaced with a er at 0°C, which was addmber at the end of each e expected large depolarand Cl channels [B. D. n, R. W. Davis, E. P. Spal, 1327 (1997)], a test of to pH 5.7 with CaOH. Roots were incubated for 10 min in DS containing 4 mM NH4Cl and 10 M, 100 M, or 1 mM Rb(86Rb)Cl and then washed two times for 10 min each in ice-cold DS. Radioactivity was measured by detection of Cerenkov radiation. 23. J. I. Schroeder, J. M. Ward, W. Gassmann, Annu. Rev. Biophys. Biomol. Struct. 23, 441 (1994); W. Gassmann, J. M. Ward, J. I. Schroeder, Plant Cell 5, 1491 (1993). 24. Y. Cao, A. D. M. Glass, N. M. Crawford, Plant Physiol. 102, 983 (1993); F. R. Vale, W. A. Jackson, R. J. Volk, ibid. 84, 1416 (1987); F. R. Vale, R. J. Volk, W. A. Jackson, Planta 173, 424 (1988). 25. Supported by the Department of Energy (DOE)/NSF/ USDA Collaborative Research in Plant Biology Program (BIR-9220331), funds to R.E.H. from the NIH University of Wisconsin Cellular and Molecular Biology Training Grant (GM07215), to M.R.S. from DOE (DEFG02-88ER13938) and NSF (DCB-90-04068), and to E.P.S. from the NASA/NSF Network for Research on Plant Sensory Systems (IBN-9416016). We thank T. Janczewski and R. Meister for technical assistance and P. Krysan, W. Robertson, J. Satterlee, and J. Young for helpful comments on the manuscript. PROBLEMS WITH THE COGNITIVE MAP THEORY Many other brain regions are involved in processing spatial info e.g., fMRI studies in humans navigating a virtual environment lly on Petri plates containKCl, and 1 mM CaCl2 in 5 days. Root protoplasts g the root about 150 m anipulator-mounted razor. infiltrated with an enzyme lysin (12 mg/ml) (Calbiol) (Sigma), and bovine seigma) dissolved in 10 mM MES, and 300 mM sorbitol [tris(hydroxymethyl)methyling a vacuum produced by 2 hours of incubation, the the solution without enC or placed in a 500- l ining 10 mM CaCl2, 30 mM 20 to180 mM sorbitol (pH sts of nonepidermal cells of the otherwise undigestere filled with 130 mM K5 mM Hepes, and 4 mM ate (Mg-ATP) (pH 7.0 with ment and procedures were and E. P. Spalding Proc. 26 November 1997; accepted 27 March 1998 Knowing Where and Getting There: A Human Navigation Network Eleanor A. Maguire,* Neil Burgess, James G. Donnett, Richard S. J. Frackowiak, Christopher D. Frith, John O’Keefe The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals. Where am I? Where are other places in the environment? How do I get there? Ques- ciencemag.org on May 13, 2011 h, A. J. Miller, Proc. Natl. 10 (1996). een an inserted electrode ts a depolarizing current to M. H. M. Goldsmith, Planta ct of which may be to un50 mV [W. Gassmann and hysiol. 105, 1399 (1994)]. itude would shift each of he most positive of which more negative than 230 poral context (3, 6). By contrast, the role of the hippocampus in human navigation has THE HIPPOCAMPUS AND SPATIAL MEMORY PROBLEMS WITH THE COGNITIVE MAP THEORY Examples of virtual reality mazes used in human studies campus, it is clear that navigation is a capacity that e in the environment. requires other brain systems as well. In addition to is maintained even if the role of sensory systems to process MEMORY THE HIPPOCAMPUS AND SPATIALand represent ved,PROBLEMS WITHenvironmental stimuli, MAP THEORY or if all distal cues THE COGNITIVE and the involvement of the field rotates with the prefrontal cortex in providing executive control of 978; Miller and Best, response selection and planning through interactions Many other brain regions are involvedDe Bruin et al., 1994; spatial cond, many place cells with cortico-striatal loops (e.g., in processing Alexander et al., 1986; found et a 2005), a number of the environment, as e.g., “Head-direction” cells areDunnett in al.,number of regions, but not the hippocampus Firing rate (spikes/s) (b) (c) 60 40 20 0 0 60 120 180 240 300 Head direction (deg) 360 ng properties. (a) Place cell: Hippocampal neuron showing an increase in firing rate whenever orner of an open-field environment. Adapted from O’Keefe J and Burgess N (1996) Head-direction cells are active only when the animal’s ce fields of hippocampal neurons. Nature 381(6581): 425–428, with permission from -direction cell: Postsubicular neuron increasingin a specific direction points its firing rate whenever the animal’s head is grees). Taken from Taube JS (2007) The head direction signal: Origins and sensory-motor 0: 181–207, with permission from the Annual Review of Neuroscience. (c) Grid cell: head info campus, it is clear that navigation is a capacity that e in the environment. requires other brain systems as well. In addition to is maintained even if the role of sensory systems to process MEMORY THE HIPPOCAMPUS AND SPATIALand represent ved,PROBLEMS WITHenvironmental stimuli, MAP THEORY or if all distal cues THE COGNITIVE and the involvement of the field rotates with the prefrontal cortex in providing executive control of 978; Miller and Best, response selection and planning through interactions Many other brain regions are involvedDe Bruin et al., 1994; spatial cond, many place cells with cortico-striatal loops (e.g., in processing Alexander et al., 1986; found et a 2005), a number of the environment, as e.g., “Head-direction” cells areDunnett in al.,number of regions, but not the hippocampus Firing rate (spikes/s) (b) (c) 60 40 20 0 0 60 120 180 240 300 Head direction (deg) 360 ng properties. (a) Place cell: Hippocampal neuron showing an increase in firing rate whenever orner of an open-field environment. Adapted from O’Keefe J and Burgess N (1996) Head-direction cells are active only when the animal’s ce fields of hippocampal neurons. Nature 381(6581): 425–428, with permission from -direction cell: Postsubicular neuron increasingin a specific direction points its firing rate whenever the animal’s head is grees). Taken from Taube JS (2007) The head direction signal: Origins and sensory-motor 0: 181–207, with permission from the Annual Review of Neuroscience. (c) Grid cell: head info lations among landmarks, not simply campus, a capacity that campus, it is clear that navigation isit is clear that navigation ssociated environment. requires other brain to a particular acue in thewith a particular cue in theother brain systems as well. In additionsystems as we requires environment. ace THEForisinstance, place celliffiring is role of sensory systems theprocess and represent to proc cell firing maintained even the maintained even if HIPPOCAMPUS AND SPATIAL to role of sensory systems MEMORY individual all distal are cues are removed, orWITHcuescues removed, or if all distalTHEORY involvement of the environmental stimuli, the PROBLEMS ifdistal THE COGNITIVE MAP cues and environmental stimuli, and the in are field rotates with the prefrontal cortex in providing exe unit (the place rotated as a unit (the place field rotates with the prefrontal cortex in providing executive control of cues; O’Keefe and Best, 1978; Miller and and response selection and planning thr nd Conway, 1978; Miller and Conway, response selection Best,planning through interactions 1980; Hill and Best, 1981 with cortico-striatal loops est, Many other brain regions are many place cells processing spatial ; (e.g., De 1981). Second, many place cells ). Second, involved loops (e.g., De Bruin et al., 1994info with cortico-striatal in Alexander et ), a number reflect the overall topographyAlexander et al., 1986;as of the environment, Dunnett et al., 2005al., 1986; Dunnett et al ll topography of the environment, as e.g., “Grid cells” are found in a subregion of the entorhinal cortex, but not the hippocampus (b) (b) 60 Firing rate (spikes/s) Firing rate (spikes/s) (a) 40 20 0 0 60 (c) (c) 60 40 20 0 120 180 240 0 300 60 360 120 180 240 300 Head direction (deg) Head direction (deg) 360 s with spatial Figure 6 cell” (a) Placespatial firing properties. (a) Place cell: Hippocampal neuron showing an increase in firing properties. in hippocampus “Place Neurons with cell: Hippocampal neuron showing an cell” ininentorhinal cortex “Grid increase firing rate whenever the animal an open-field environment. Adapted from O’Keefe J and Burgess N from he North-West corner ofenters the North-West corner of an open-field environment. Adapted (1996)O’Keefe J and Burg Geometric of hippocampal neurons. fields of hippocampal neurons. Nature 381(6581): inants of the place fields determinants of the place Nature 381(6581): 425–428, with permission from 425–428, with per Macmillan Publishers Ltd. ers Ltd. (b) Head-directioncells” are (b) Head-direction cell: Postsubicularwhenever the animal’sfiring rate whenever neuron increasing its “Grid cell: Postsubiculardegrees). Taken from firing rate (2007) The head direction signal: Origins a much less influenced by neuron increasing info is non-spatial its head facing a particular direction JS Taube JS direction (60 degrees). Taken from Taube(60 (2007) The head direction signal: Origins and sensory-motor that “place cells” Neuroscience.Annual Review of Neuroscience. integration. Annu. Rev. Neurosci. 30: 181–207, Review of Rev. Neurosci. 30: 181–207, with permission from the Annualwith permission from the (c) Grid cell: Dorsocaudal medial entorhinal spatial firing fields arranged in a spatial firing fields arranged in al entorhinal cortex neuron exhibiting multiplecortex neuron exhibiting multiple hexagonal grid in an open field.a hexagonal THE HIPPOCAMPUS AND SPATIAL MEMORY PROBLEMS WITH THE COGNITIVE MAP THEORY But the biggest problems for the theory are that: Damage to the hippocampus impairs non-spatial memory tasks Hippocampal cells code non-spatial information as well We’ll talk about a few of those examples now OVERVIEW ❖ Why use animals to investigate the role of the hippocampus in learning and memory? ❖ The hippocampus and spatial learning/memory ❖ The hippocampus as a cognitive map ❖ Problems with that theory ❖ The hippocampus and non-spatial learning/memory ❖ So what does the hippocampus do? THE HIPPOCAMPUS AND NON-SPATIAL MEMORY FLEXIBILITY OF EXPRESSION OF NON-SPATIAL REPRESENTATIONS Hippocampal damage impairs “flexibility of expression” of non-spatial memory representations (“~non-spatial maps”) Bunsey & Eichenbaum (1996) better than that of both the PRER (P ⌅ 0.01) and rise above chance levels subjects (P ⇥ 0.10) or in control across both pairs, performance did not FX (P ⌅ hoc comparisons indicated that control performance was 0.01) ⌅ better than that of both the PRER (P ⌅ 0.01) and FX (P groups, which did not significantly0.10) or FX each (P ⇥ 0.10). subjects performed significantly [ in control subjects (P ⇥ differ from rats other PRER (P ⇥ 0.10). In subjects performed significantly [t(5) ⇤ 2.988; P ⌅ 0.05], albeit better than chance (Fig. 3 addition, by contrast to the performance of other slightly, 0.01) groups, which did not significantly differ from each other FX subjects, slightly, better than chance (Fig. 3the ANOVA confirmed that the two subjects removed from B). FX group there were no significant group (P ⇥ 0.10). In addition, by contrast to the performance of other because performance [F(2, 15) ⇤ 0.221 FX subjects, the two subjects removed from the FX group of ineffective lesions significant group differences of new probe there were no performed within the range on control controls because of ineffective lesions performed within the range of performance on BD F(2, and 80% correct).⇥ 0.10]. Furthermore, performed significantly performance [ (70 15) ⇤ 0.221; P A further analysis ofperformed significantly better on BD trials than odor pairs [t(7) ⇤ 3.529; P ⌅ new on control performance on BD (70 and 80% correct). controls transitivity examined performance on the on presentation of the BD pair, which may be A further analysis of transitivity examined performance very firstnew odor pairs [t(7) ⇤ 3.529; P ⌅ 0.01] whereas PRER rats FX not (Ps ⇥ 0.10). The con and did considered a ‘‘pure’’ test of inferential The contrast between robust mance on BD over new odor p the very first presentation of the BD pair, which may be rats did not (Ps ⇥ 0.10). responding uncontamperforinated indicates considered a ‘‘pure’’ test of inferential responding uncontam-by reinforcement BD repeated probe trials. Of control rats strongly that their judgments mance on on over new odor pairs in choose that their the first BD the BD pairs reflected inferential capacity. Conversely, inated by reinforcement on repeated probe trials. Of subjects, 88%indicates correctly on judgments onpresentation control (binomial difference on this comparison, c subjects, 88% choose correctly on the first BD presentation P ⌅ 0.05) whereas only Conversely, FX and PRER a significant inferential capacity. 50% of the the absence of successful on this comparison, combined with (binomial P ⌅ 0.05) whereas only 50% of the FX andsubjects were difference on the initial BD judgment (binomialintact mance on the AE pair, emphasi PRER perforP ⇥ 0.10). mance on the AE pair, emphasizes the selective losscapacity for transitive inference subjects were successful on the initial BD judgment (binomial of the Analyses of performance on other types of FX andtrials P ⇥ 0.10). capacity for transitive inference in probe PRER rats. demonstrated the selectivity of the deficit in transitive inferAnalyses of performance on other types of probe trials DISCUSS ence in demonstrated the selectivity of the deficit in transitive infer- rats with hippocampal region damage. All rats perDISCUSSIONbe solved Previous studies have demonstra formed ence in rats with hippocampal region damage. All rats per- extremely well on the AE trials, which can cies can Previous studies (Fig. 3B), and there was no formed extremely well on the AE trials, which can bewithout a transitive judgmenthave demonstrated that several animal spe- learn an overlapping serie solved and demonstrate a capacity for cies difference in performance on this problem without a transitive judgment (Fig. 3B), and there significant group can learn an overlapping series of discrimination problems was no FIG. 2. significant group difference in performance on this problem ( A )(2, 15) ⇤ 0.595; P of trials required representtheinferencefor each phase of premise training. Err ( A ) The mean number of trials required to reach the criterionIG. 2.eachF The mean number ⇥ 0.10]. Conversely, all SE criterion (15, 26– present results identify F for [ANOVA: phase of premise training. Error bars to reach groups the 32). The and demonstrate a capacity for transitive above mean. ( B ) Mean response accuracy ( SE) on each of the four premise pairs during the evidence of learning during presentations of pairs duringto transitive inference and mean. ( B Mean response accuracy ( SE) critical 32). The present identify the four premise [ANOVA: F(2, 15) ⇤ 0.595; P ⇥ 0.10]. Conversely, allshowed )minimal test sessions. results on each ofthe hippocampal region as the test sessions. groups the of (WX and pus plays showed minimal evidence control performance was hoc new odor pairs indicated YZ). Combining theindicate that the hippocam- a pairs, performancedev of learning during presentationscomparisonspairs, performance did not performance was levels across both critical role in the did critical to transitive inference rise above chance and performance across both hoc comparisons indicated that that control the new of both the PRER YZ). 0.01) and FX P ⌅ betterin pus plays P PRER in the development or PRER expresbetter than that odor pairs (WX and (P ⌅ Combining the(performance control subjectsathe⇥ 0.10) (P ⌅ 0.01) and⇥ 0.10).⌅ than that of both (critical roleor FX rats (P FX (P flexiblein control subjects (P ⇥ 0.10) or THE HIPPOCAMPUS AND NON-SPATIAL MEMORY MEMORY FOR RELATIONSHIPS AMONG NON-SPATIAL ITEMS Hippocampal damage impairs “transitive inference” in non-spatial representations (analogous to thinking of a new trajectory between 2 locations) Hipocampal rats cannot express the “hidden” Sci. 10 Psychology: Dusek and Eichenbaum Proc. Natl. Acad. relationship among from P ⌅5 items the other Hippocampal rats can learn set groups, which did not significantly differ from each other 0.01) groups, which did not significantlyt(5) ⇤ 2.988; each0.05], albeit subjects performed significantly [t 0.01) of overlapping subjects performed significantly [ differ (P by contrast slightly, better than chance to 3 ). ANOVA of other 110 Psychology: Dusek and⇥ 0.10). In addition, by contrast to the performance of other (P ⇥ 0.10). In addition,subjects (Fig.theBperformanceconfirmed that slightly, better than chance (Fig. 3 Proc. Natl. Acad. Sc FX Eichenbaum there the two no group from the pairs of odors as well as controlslesions removed within the range of because of ineffectivesignificantremoveddifferences on newof there were no[Fsignificant group ble 1. Stages of training and probesubjects, the two subjectsperformedfrom the FX group FX subjects,were were combinedFX groupprobeanalyses below tests because of ineffective lesions ⇤ 0.221; performance [F(2, 15) performedPwithin the range the performance ⇥ 0.10]. in Furthermore, (2, 15) ⇤ 0.221 control performance on BD (70 and 80% correct). control performance on BD (70 and 80% correct). trials than on controls performed significantly controls performed significantly better on BD as the control group. odor pairs (7) ⇤ 3.529; ⌅ 0 further analysis of transitivity further analysis t transitivity ⌅ 0.01] performance and new odor pairs ⇤ 3.529; Premise pair training theA very first presentation of theexamined performance on theA very firstnot (Ps[of(7)0.10). ThePexaminedwhereas PRERon FX new did not (Ps[t⇥ 0.10). ThePcont BD pair, which may be pair, which may perforrats did presentation of thecontrast between robustbe ⇥ able 1. Stages of training and probe tests test of inferential responding uncontam- considered a on BD test ofnew odorBDrespondingandin the analyses beloi were combined strongly rats on BDDuring pa considered a ‘‘pure’’ uncontammance ‘‘pure’’ over inferential pairs in rats Shaping. over Apparatuscontrol control mance that their new odor o inated by reinforcement on repeated probe trials. Of control inated by reinforcement on repeated probe trials. Of indicates that their judgments on the BD pairs reflected indicates judgments A B subjects, 88% choose correctly on the first BD presentation subjects, 88% choose asConversely, the absence of4-oz Nalgene plastic c correctly on first BD a agroup. inferential capacity. thethe withpresentation significant capacity. Conversely, providedcontrolintact perfor- inferential on this comparison, co (binomial Premise pair training P ⌅ 0.05) whereas only 50% of the FX and PRER (binomial P ⌅ 0.05)this comparison, combined with PRER difference difference on whereas only 50% of the FX and B C subjects were successful on the initial BD judgment (binomial subjects wereon the AE on Apparatus (binomial the mance on the AE During the initial BD the mance successful pair, emphasizesjudgment and Shaping. pair, emphasiz diameter) FX selective loss of 110 g of san filled rats. capacity PRER with A BC D P ⇥ 0.10). of performance on other types of probe trials P ⇥ 0.10). of for transitive inference intypesand probe trials capacity for transitive inference i Analyses Analyses performance on other of provided with a ⇥ (6.5 selectivity of the deficit in transitive 4-oz Nalgene plasti DISCUSSION DISCUSS B C D demonstratedwith hippocampal region damage. All ratsinfer- demonstratedwith Plexiglas baseAll ratsinfer- 3.5 in). A cup wa E rats the selectivity of the deficit in transitive per- ence in rats the hippocampal region damage. ence in perPrevious studiesdiameter) filled formed extremely well on the AE trials, which can be solved formed extremelyrewards (Froot be solved with 110 have demonstrat well have demonstrated that several animal spe- Previous studies g of sa on the AE trials, which can Loops, Kellogg’s, Bat C D cies transitive overlapping series of discrimination no without Ordered representation a transitive judgment (Fig. 3B), and there was no without acan learn anjudgment (Fig. 3B), and there wasproblems cies can learn an overlapping serie and group partially transitive inference (15, ⇥ 3.5 topA cup t significant group difference in performance on this problem significantdemonstrate a capacity for buried problem 26– andon in). a capacity for w difference in performance on this (6.5 Plexiglas base in and demonstrate of the 32). F(2, 15) ⇤ results ⇥ 0.10]. the identify region [ANOVA: A relationship among Fitems of Plearning during presentations of showedcanpresent0.595; Plearning duringhippocampalhippocam- relationshipidentify B C D Dshowed E (2, 15) ⇤ 0.595; ⇥ 0.10]. Conversely, all groups [ANOVA:The transitive inference and Conversely, all groups as 32). The present results and E minimal evidence “hidden” minimal express the a simpler presentations the Both groupscritical to a evidence ofYZ). Combining thethatflexibleof criticaland thenthere rewardsindicate performance pus plays atransitiverole in deve (Froot Loops, Kellogg’s, B of the rat’s home cage, to critical inference the new (WX role pus plays criticaland in the development or Ordered Probe tests representationodor pairs (WX and YZ). Combining the performance the new odoripairsa control condition expresn were visible. Subsequently, subjects partially buried in and on top of th B A D: test C transitivity vs. B of D E of the rat’s home cage, and then scented sand in two cups mounted on Probe E: nontransitive novel pairing A vs. tests were visible. Subsequently, reward only one cup contained food subject B vs. D: test of transitivity scented sand in two cups mounted o with a simple odor discrimination ta A vs. E: nontransitive novel pairing memory deficit whereas severe memory deficits are obonly one cup contained food rewa native stimuli consisted of common f rved when the damage includes the cortical regions adjacent with a each of two discrimination sand. On simple odor 10-trial sessions o hippocampus in both rats (16, 17) and monkeys (18–20). thememory deficit whereas severe memory deficits are obnative cups of sand; one common with twostimuli consisted ofcontainin erved when have led some to suggest that the hippocampus ese findings the damage includes the cortical regions adjacent a sand. On each reward,10-trial sessio single buried of two and the othe o plays either a relatively rats (16, 17) role in memory (20) elfthe hippocampus in bothunimportant and monkeys (18–20). with two cups of response was de unbaited. A choicesand; one contain Dusek & Eichenbaum (1998) ahese findingsto spatial memory suggestwhereas the adjacent role limited have led some to (6, 10) that the hippocampus a single buried reward, and the ot which a subject began to dig although FIG. 3. ( A ) Mean response accuracy (⇧SE) for the average performance on premise pairs BC and CD and fo the test sessions. ( B ) Response accuracy ⇧SE) for control probe pair AE and the average response accuracy for FIG. 3. ( A ) Mean response accuracy (⇧SE) for the average performance on premise pairs BC and(CD and for the critical test pair BD during YZ). the test sessions. ( B ) Response accuracy (⇧SE) for control probe pair AE and the average response accuracy for the new control pairs (WX and YZ). FIG. 3. ( A ) Mean response accuracy (⇧SE) for the average performance 3. premise pairs BC and CD and(for thefor the average performance on premise pairs BC and CD and for FIG. on ( A ) Mean response accuracy ⇧SE) critical test pair BD during the test sessions. ( B ) Response accuracy (⇧SE) for control probe pair AE and the average Response accuracy for SE) newcontrol probe (WXAE and the average response accuracy for the test sessions. ( B ) response accuracy (⇧ the for control pairs pair and WHAT ARE THESE CELLS CODING FOR? • • • Wood et al (2000) THE HIPPOCAMPUS AND NON-SPATIAL MEMORY HIPPOCAMPAL CELLS ENCODE MORE THAN JUST SPATIAL INFO • • • Wood et al (2000) THE HIPPOCAMPUS AND NON-SPATIAL MEMORY HIPPOCAMPAL CELLS ENCODE MORE THAN JUST SPATIAL INFO Hippocampal cells also code for non-spatial info in a non-spatial task (Task: “Does current odor match the odor from the last trial?”) hippocampal(neurons( erform(a(match/non5 udgment(at(different( s(in(an(environment( Place(cell( Place cells Match/nonmatch(cell( Approach cells • Approach(cell( Odor cells Match/nonmatch cells • • o,(and(Eichenbaum,(1999( Wood et al (1999) THE HIPPOCAMPUS AND NON-SPATIAL MEMORY HIPPOCAMPAL CELLS ENCODE MORE THAN JUST SPATIAL INFO Recording single neurons in humans subjects (very rare!) Individual neurons coding for specific experiences (more on that next lecture) OVERVIEW ❖ Why use animals to investigate the role of the hippocampus in learning and memory? ❖ The hippocampus and spatial learning/memory ❖ The hippocampus as a cognitive map ❖ Problems with that theory ❖ The hippocampus and non-spatial learning/memory ❖ So what does the hippocampus do? SO WHAT DOES THE HIPPOCAMPUS DO? PUTTING IT ALL TOGETHER: THE “RELATIONAL MEMORY THEORY” The hippocampus is important for creating a “relational network”, in which spatial and non-spatial info is encoded and can be flexibly expressed The hippocampus encodes relations among spatial stimuli The hippocampus encodes relations among non-spatial stimuli It’s a “memory space”, not memory for space! ...
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