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by a careful analysis of thethree-dimensional structure ofa dividing nucleus and the ER, similarto what was done for interphaseS. cerevisiae cells [20]. In particular,it would be of interest to explore ifany specific architectural featuresat the mitotic NE–ER interface couldserve as a specialized membranereservoir for the NE expansion.

At present, it would be prudent toconclude that we know very little aboutthe mechanisms underlying NEexpansion during mitosis and the fieldis ripe for major breakthroughs. Theflared mitotic nuclei described byWitkin et al. [4] should prove a usefulexperimental setup for dissecting thenuclear growth pathways. While oftenconsidered somewhat esoteric, theclosed mitosis is in fact a great systemfor understanding non-scalable nuclearmembrane expansion and nuclearshape control in all eukaryotes.

References1. Cavalier-Smith, T. (2005). Economy, speed and

size matter: evolutionary forces driving nucleargenome miniaturization and expansion. Ann.Bot. 95, 147–175.

2. Jorgensen, P., Edgington, N.P.,Schneider, B.L., Rupes, I., Tyers, M., andFutcher, B. (2007). The size of the nucleusincreases as yeast cells grow. Mol. Biol. Cell 18,3523–3532.

3. Neumann, F.R., and Nurse, P. (2007). Nuclearsize control in fission yeast. J. Cell Biol. 179,593–600.

4. Witkin, K.L., Chong, Y., Shao, S., Webster, M.,Lahiri, S., Walters, A.D., Lee, B., Koh, J.L.Y.,Prinz, W.A., Andrews, B.J., et al. (2012). Thebudding yeast nuclear envelope adjacent to thenucleolus serves as a membrane sink duringmitotic delay. Curr. Biol. 22, 1128–1133.

5. Webster, M.T., McCaffery, J.M., andCohen-Fix, O. (2010). Vesicle traffickingmaintains nuclear shape in Saccharomycescerevisiaeduringmembraneproliferation. J.CellBiol. 191, 1079–1088.

6. Siniossoglou, S., Santos-Rosa, H.,Rappsilber, J., Mann, M., and Hurt, E. (1998). Anovel complex of membrane proteins requiredfor formation of a spherical nucleus. EMBO J.17, 6449–6464.

7. Santos-Rosa, H., Leung, J., Grimsey, N.,Peak-Chew, S., and Siniossoglou, S. (2005).The yeast lipin Smp2 couples phospholipidbiosynthesis to nuclear membrane growth.EMBO J. 24, 1931–1941.

8. Levy, D.L., and Heald, R. (2010). Nuclear size isregulated by importin alpha and Ntf2 inXenopus. Cell 143, 288–298.

9. Carman, G.M., and Han, G.S. (2006). Roles ofphosphatidate phosphatase enzymes in lipidmetabolism. Trends Biochem. Sci. 31, 694–699.

10. O’Hara, L., Han, G.S., Peak-Chew, S.,Grimsey, N., Carman, G.M., andSiniossoglou, S. (2006). Control of phospholipidsynthesis by phosphorylation of the yeastlipin Pah1p/Smp2p Mg2+-dependentphosphatidate phosphatase. J. Biol. Chem.281, 34537–34548.

11. Loewen, C.J., Gaspar, M.L., Jesch, S.A.,Delon, C., Ktistakis, N.T., Henry, S.A., andLevine, T.P. (2004). Phospholipid metabolismregulated by a transcription factor sensingphosphatidic acid. Science 304, 1644–1647.

12. Choi, H.S., Su, W.M., Morgan, J.M., Han, G.S.,Xu, Z., Karanasios, E., Siniossoglou, S., andCarman, G.M. (2011). Phosphorylation ofphosphatidate phosphatase regulates itsmembrane association and physiologicalfunctions in Saccharomyces cerevisiae:identification of SER(602), THR(723), ANDSER(744) as the sites phosphorylated byCDC28 (CDK1)-encoded cyclin-dependentkinase. J. Biol. Chem. 286, 1486–1498.

13. Choi, H.S., Su, W.M., Han, G.S., Plote, D., Xu, Z.,and Carman, G.M. (2012). Pho85p-Pho80pphosphorylation of yeast Pah1p phosphatidatephosphatase regulates its activity, location,abundance, and function in lipid metabolism. J.Biol. Chem., In Press. 10.1074/jbc.M112.346023.

14. Karanasios, E., Han, G.S., Xu, Z., Carman, G.M.,and Siniossoglou, S. (2010). Aphosphorylation-regulated amphipathic helixcontrols the membrane translocation andfunction of the yeast phosphatidatephosphatase. Proc. Natl. Acad. Sci. USA 107,17539–17544.

15. Adeyo, O., Horn, P.J., Lee, S., Binns, D.D.,Chandrahas, A., Chapman, K.D., andGoodman, J.M. (2011). The yeast lipinorthologue Pah1p is important for biogenesis oflipid droplets. J. Cell Biol. 192, 1043–1055.

16. Castagnetti, S., Oliferenko, S., and Nurse, P.(2010). Fission yeast cells undergo nucleardivision in the absence of spindle microtubules.PLoS Biol. 8, e1000512.

17. Campbell, J.L., Lorenz, A., Witkin, K.L.,Hays, T., Loidl, J., and Cohen-Fix, O. (2006).Yeast nuclear envelope subdomains withdistinct abilities to resist membrane expansion.Mol. Biol. Cell 17, 1768–1778.

18. Stone, E.M., Heun, P., Laroche, T., Pillus, L.,and Gasser, S.M. (2000). MAP kinase signalinginduces nuclear reorganization in buddingyeast. Curr. Biol. 10, 373–382.

19. Towbin, B.D., Meister, P., and Gasser, S.M.(2009). The nuclear envelope–a scaffold forsilencing? Curr. Opin. Genet. Dev. 19, 180–186.

20. West, M., Zurek, N., Hoenger, A., andVoeltz, G.K. (2011). A 3D analysis of yeast ERstructure reveals how ER domains areorganized by membrane curvature. J. Cell Biol.193, 333–346.

1Temasek Life Sciences Laboratory,1 Research Link, 117604 Singapore..2Department of Biological Sciences NationalUniversity of Singapore, 117604 Singapore.*E-mail: snejana@tll.org.sg

DOI: 10.1016/j.cub.2012.04.043

Animal Memory: Rats Can AnswerUnexpected Questions about PastEvents

A new study has found that rats are able to answer, in a hippocampus-dependent manner, unexpected questions about whether they recently atefood or not. The results highlight potential shared mechanisms forremembering personal events in rats and humans, and offer new insightsinto the nature of animal memory.

Michael J. Beran

‘‘And where were you last night?’’No matter who asks you thisquestion — the inquisitive neighbor,the jealous lover, or the detectiveinterviewing you in the policestation — the experience is likely to besimilar. You will mentally ‘travelthrough time’ to the previous evening,remembering the critical ‘who, what,

when, and where’ information relevantto the question being asked. You mayeven, in some cases, feel as if you werere-living the evening in question.These experiences are routine forhumans, and highlight the personal andspecific aspects of our memory forevents. An important question iswhether these experiences areuniquely human, or whether otheranimals have access to the same kinds

of memories for specific events andepisodes in their own past. This form ofmemory, called episodic memory, andthe question of whether other speciesexperience mental time travel into thefuture and into the past, as whenhumans recall personal episodes, isheavily debated in the comparativecognition literature [1,2]. A studyreported in this issue ofCurrent Biology[3] will certainly add to the debateabout episodic memory in animals:Zhou et al. [3] report that rats haveand use episodic memories that allowthem to answer unanticipatedquestions about their own personalpast. These new data are exciting,and will inspire new discussionsabout the nature of animal memory,and specifically the existence ofepisodic memory in nonhumananimals.There have been a number of

studies with nonhuman animals that

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suggested episodic-like memory.Perhaps best known among these arestudies with scrub jays, in which thebirds cache food items of differentquality, and different decompositionrates, and then seemingly rememberwhen and where they cached what, byretrieving the better (but moreperishable) items after short delays andthe less preferred (but longer-lasting)items after longer delays [4,5]. Otherstudies have assessed so-calledwhat-where-when memory usinga variety of tasks, with mixed results[6–9]. And, a few cases have involvedtests with great apes in whichexperimenters could actually query anape about what it remembers [10], or anape could recall and report itsmemory for a past event [11]. However,these reports have been met withvarious criticisms, particularlyregarding whether they really provedthat animals can ‘mentally travelthrough time’ as would seem to bea critical aspect of episodic memory[12]. Thus, it remains an openquestion as to how to demonstrateepisodic memory in nonhumananimals [13–16].

Zhou et al. [3] expanded upon theirown creative memory tests given torats to provide the newest evidencefor episodic memory in nonhumananimals. Rats were trained on twokinds of tests. In the first, they wereplaced in a maze that had five alleys,three of which were open and had foodat the end. The rats were allowed tovisit these three alleys, and then had toendure a delay. After the delay, fivealleys were opened, and food was atthe end of the two not previouslyvisited. The rats were quite good atgoing down those alleys rather than thealready visited alleys where no morefood remained. The rats also learned tonavigate a T-maze. At the start ofa trial, a rat either got food or did not:food delivery (or not) was the cue as towhich way to turn at the end of themaze to retrieve additional fooditems — one direction if the rat hadjust eaten food, and the other if ithad not.

The rats performed both of thesetests until they were quite good atremembering where food still waslocated, and remembering whetherthey had just eaten food. Then, incritical test trials, rats ran down threearms of the radial maze as before. Now,however, they either got food at the endof each alley (as before) or they did not.

Then, they were given the T-maze test,where they had to respond based onwhether they had just received foodfrom the radial maze test or had not.These critical probe tests wereinfrequent, and were unlike the usualtests with just onemaze or the other, sothe rats could not come to anticipatewhen they might get this unusualcombination of mazes. Zhou et al. [3]argue that the rats were incidentallyencoding the presence (or absence) offood in the radial arm maze, rather thanin response to some expectation ofbeing asked (in the T-maze) aboutgetting food. This is a critical aspect ofthe experiment, because it would meanthat rats that accurately commented ongetting (or not getting) food earlier inthe radial arm maze would have to bedoing so when the question wasunexpected. They would have toaccess their episodic memory for thatevent, rather than using a plannedresponse due to expecting the T-mazequestion to be asked (a responsepattern that would not require episodicmemory).

The story getsmore interesting. Zhouet al. [3] then temporarily inactivatedthe CA3 region of the hippocampus insome rats, and found very selectiveeffects on performance in these tasks.The hippocampus has been implicatedas a critical brain region for episodicmemory in humans [17,18] and also inother animals [19,20]. So, Zhou et al. [3]predicted that if these rats werenormally encoding episodic memoriesof whether they had eaten food or not,disruption of processing in thehippocampus would hurt theperformance pattern in the T-maze thatrelied on those episodic memories.This is exactly what happened.Interference occurred only forunexpected questions, but not formore general responding in the T-mazewhen an expected question was asked,and the rats presumably couldimplement a planned action pattern. Itseemed clear that hippocampusinvolvement was necessary for the ratsto encode episodes of eating (or noteating) that they could later retrievewhen the unexpected question wasasked.

It is not clear, andmay never be clear,what the experience is like for a rat(or any nonhuman animal) to rememberpast events in its life. The issuessurrounding mental time travel inanimals, and the subjective qualitiesof memory in other species are

important, and should be debatedand considered carefully. But, resultssuch as these are exciting for whatthey offer by way of animal models ofcognitive processes that likely sharesome qualities with thoseexperienced and used by humans.That rats show some similarities in thebrain–behavior links for memoryprocesses offers valuable newinsights to better understandinganimal memory and human memory,and also for advancing potentialtherapeutic treatments for peoplesuffering from memory deficits.

References1. Griffiths, D., Dickinson, A., and Clayton, N.

(1999). Episodic memory: What can animalsremember about their past? Trends Cogn. Sci.3, 74–80.

2. Suddendorf, T., and Corballis, M.C. (2007). Theevolution of foresight: What is mental timetravel, and is it unique to humans? Behav.Brain Sci. 30, 299–351.

3. Zhou, W., Hohmann, A.G., and Crystal, J.D.(2012). Rats answer an unexpected questionafter incidental encoding. Curr. Biol. 22,1149–1153.

4. Clayton, N.S., and Dickinson, A. (1998).Episodic-like memory during cache recoveryby scrub jays. Nature 395, 272–274.

5. Clayton, N.S., and Dickinson, A. (1999). Scrubjays (Aphelocoma coerulescens) remember therelative time of caching as well as the locationand content of their caches. J. Comp. Psychol.113, 403–416.

6. Hampton, R.R., Hampstead, B.M., andMurray, E.A. (2005). Rhesus monkeys(Macaca mulatta) demonstrate robust memoryfor what and where, but not when, in anopen-field test of memory. Learn. Motiv. 36,245–259.

7. Skov-Rackette, S.I., Miller, N.Y., andShettleworth, S.J. (2006). What-where-whenmemory in pigeons. J. Exp. Psychol. Anim.Behav. Proc. 32, 344–358.

8. Feeney, M.C., Roberts, W.A., and Sherry, D.F.(2009). Memory for what, where, and when inthe black-capped chickadee (Poecileatricapillus). Anim. Cogn. 12, 767–777.

9. Hoffman, M.L., Beran, M.J., andWashburn, D.A. (2009). Memory for ‘what,’‘where,’ and ‘when’ information in rhesusmonkeys (Macaca mulatta). J. Exp. Psychol.Anim. Behav. Proc. 35, 143–152.

10. Schwartz, B.L., Colon, M.R., Sanchez, I.C.,Rodriguez, I.A., and Evans, S. (2002).Single-trial learning of ‘‘what’’ and ‘‘who’’information in a gorilla (Gorilla gorilla gorilla):Implications for episodic memory. Anim. Cogn.5, 85–90.

11. Menzel, C.R. (1999). Unprompted recall andreporting of hidden objects by a chimpanzee(Pan troglodytes) after extended delays. J.Comp. Psychol. 113, 426–434.

12. Suddendorf, T., and Busby, J. (2003). Mentaltime travel in animals? Trends Cogn. Sci. 7,391–396.

13. Eichenbaum, H., Fortin, N.J., Ergorul, C.,Wright, S.P., and Agster, K.L. (2005). Episodicrecollection in animals: ‘‘If it walks like a duckand quacks like a duck.’’. Learn. Motiv. 36,190–207.

14. Griffiths, D.P., and Clayton, N.S. (2001). Testingepisodic memory in animals: A new approach.Physiol. Behav. 73, 755–762.

15. Roberts, W.A., and Feeney, M.C. (2009). Thecomparative study of mental time travel. TrendsCogn. Sci. 13, 271–277.

16. Zentall, T.R. (2005). Animals may not be stuckin time. Learn. Motiv. 36, 208–225.

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17. Tulving, E., and Markowitsch, H.J. (1998).Episodic and declarative memory: Role of thehippocampus. Hippocampus 8, 198–204.

18. Ergorul, C., and Eichenbaum, H. (2004). Thehippocampus and memory for ‘‘what,’’ ‘‘where,’’and ‘‘when.’’ Learn. Memory 11, 397–405.

19. Li, J.S., and Chao, Y.S. (2008). Electrolyticlesions of dorsal CA3 impair episodic-like

memory in rats. Neurobiol. Learn. Mem. 89,192–198.

20. Kesner, R.P., Hunsaker, M.R., andWarthen, M.W. (2008). The CA3 subregion ofthe hippocampus is critical for episodicmemory processing by means of relationalencoding in rats. Behav. Neurosci. 122,1217–1225.

Language Research Center, Georgia StateUniversity, University Plaza, Atlanta,GA 30302, USA.E-mail: mjberan@yahoo.com

DOI: 10.1016/j.cub.2012.05.003

Cytoskeletal Organization: Whirlingto the Beat

Dense populations of microtubules driven by axonemal dynein form largevortices, providing insights into how simple interactions between individualscan give rise to large-scale coordinated movement, such as that seen inschools of fish and flocks of birds.

William O. Hancock

Like busy sidewalks, schools of fish,and confluent monolayers of cells, thecytoplasm is a crowded environmentwhere larger order organization resultsfrom numerous interactions betweenpairs of individuals. These interactionsare particularly important forcytoskeletal filaments, which have highaspect ratios and frequently function inaligned bundles, such as in the mitoticspindle, axonal transport, and musclefibers. Can we relate the molecularmechanisms that promote cytoskeletalorganization to the collective groupbehaviors seen at the level of cellsand organisms? A recent paper bySumino et al. [1] describes coordinatedmovements of groups of microtubulesdriven by dynein motors and suggeststhat the complex emergent behaviorobserved in this refined systemcan help to understand not onlycytoskeletal organization but alsothe coordinated movements of morecomplex systems, such as confluentmonolayers of cells and schoolingof fish.

To understand how simpleinteractions between pairs ofindividuals lead to coordinatedbehavior of groups, Sumino et al. [1]turned to the filament gliding assay,a workhorse in the molecular motorsfield. Axonemal dynein c motors,which power the beating of cilia andflagella, were adsorbed to a glasssurface at high surface densities,and microtubules introduced inthe presence of ATP. Using lowconcentrations of microtubules, thefilaments glided across the surface

at a few microns per second, takingfairly straight paths and not interactingwith any neighbors (think lone hiker ina field). Increasing the filament densityto the point where many collisionsoccurred (mimicking a crowded urbanenvironment) led to groups of filamentsmigrating together and organizinginto vortices with diameters that were25-fold larger than the filament lengths.Over time, the vortices organized intoa quasi-lattice on the surface, withmicrotubules switching betweenadjacent vortices (Figure 1A).

This type of coordinated movementis observed in crowded systems ata range of size scales. Pedestriansself-organize into lanes on crowdedsidewalks and, under normalconditions, people efficiently exitcrowded theatres and avoid jamming[2]. Flocks of birds and schools of fishinvolve many individuals moving in thesame direction and rapidly switchingdirections en masse, behaviors thatare evolutionarily adapted to avoidor confuse predators [3]. Marchinglocusts and groups of ants showcollective behavior, sometimes todevastating effect [4,5]. In some ofthese cases, the collective migrationforms into a circle or vortex, whicheliminates the need for a leader andonly requires individuals to follow theindividuals in front of them (Figure 1B)[4,6]. This collective behavior has beenthe subject of extensive experimentalanalysis and modeling, but, becauseindividuals can make consciousdecisions, it is often difficult to pindown the underlying rules that resultin the emergent behavior at theorganismal level.

Highly aligned collective motion isalso seen at the level of individual cellsand is relevant for understandingwound healing and the properties ofbacterial biofilms. In sheets of epithelialcells and in plates of migratingbacteria, groups of cells migrating enmasse have been observed (Figure 1C)[7,8]. In dense cultures of migrating fishkeratocytes, erecting microfabricatedbarriers resulted in the cells movingin a circular pattern [9]. Even in theserelatively simple systems, however, therange of possible cell–cell interactionsthat give rise to the emergent behaviormakes it difficult to constrain modelsof the behavior. This is why studyingcollective motion in a highly reducedsystem like the filament assay isappealing — the rules governinginteractions between individuals canbe quantitatively characterized toconstrain models of the complexbehavior of groups.To define the ‘interaction rules’ in

the dynein–microtubule gliding assay,Sumino et al. [1] characterizedcollisions between individualmicrotubules at low microtubuledensities and found that collisionsmost often caused alignment of themoving filaments, either in the parallelor antiparallel direction depending onthe angle of interaction. This contrastswith collisions of microtubules drivenby immobilized kinesin motors,where microtubules most oftencross over one another withoutany change in direction [10] — moreon that later. Using the rules formicrotubule–microtubule collisions,a computational model was developedand the model was shown to nicelyreproduce the vortex behavior. Hence,very simple interactions betweenindividuals, which don’t require cellularmechanotransduction or cognitivedecision making, can lead to complexbehaviors of groups on scales manytimes larger than the size of theindividual.Why do the dynein-driven

microtubules (which average 15