Abstract
Episodic memory is defined by the temporal organization of events in specific experiences. The hippocampus plays an essential role in episodic memory, suggesting that studies on temporal processing by the hippocampus might offer insights in the mechanisms of episodic memory. Here, we review reports on the effects of hippocampal damage in humans and animals and physiological studies using brain imaging in humans and single neuron recordings in animals. These studies provide converging and compelling evidence that the hippocampus is critical for the temporal organization of memories in humans and animals, including when spatial cues are irrelevant. Furthermore, the hippocampus in engaged in humans associated with temporal processing of memories, and hippocampal neuronal networks in animals and humans represent the temporal organization of experiences and disambiguate overlapping temporally extended experiences. In particular, hippocampal “time cells” fire at particular moments during temporally structured experiences, much as hippocampal place cells fire associated with particular locations in spatially organized experiences. Comparisons of firing properties of hippocampal neurons across species and behavioral situations suggest that the hippocampus provides a temporal and spatial “scaffolding” that organizes events to compose episodic memories.
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Adlam AL, Vargha-Khadem F, Mishkin M, de Haan M (2005) Deferred imitation of action sequences in developmental amnesia. J Cogn Neurosci 17:240–248
Agster KL, Fortin NJ, Eichenbaum HB (2002) The hippocampus and disambiguation of overlapping sequences. J Neurosci 22:5760–5768
Ainge JA, Tamosiunaite M, Woergoetter F, Dudchenko PA (2007) Hippocampal CA1 place cells encode intended destination on a maze with multiple choice points. J Neurosci 27:9769–9779
Allen K, Rawlins JN, Bannerman DM, Csicsvari J (2012) Hippocampal place cells can encode multiple trial-dependent features through rate remapping. J Neurosci 32:14752–14766
Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:571–591
Barker GR, Warburton EC (2011) When is the hippocampus involved in recognition memory? J Neurosci 31:10721–10731
Bartsch T, Döhring J, Rohr A, Jansen O, Deuschl G (2011) CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness. Proc Natl Acad Sci USA 108:17562–17567
Brown TI, Ross RS, Keller J, Hasselmo ME, Stern CE (2010) Which way was I going? Contextual retrieval supports the disambiguation of well-learned overlapping navigational routes. J Neurosci 30:7414–7422
Buhusi V, Meck WH (2005) What makes us tick? Functional and neural mechanisms of interval timing. Nat Rev Neurosci 6:755–765
Buzsaki G, Moser EI (2013) Memory, navigation, and theta rhythm in the hippocampal-entorhinal system. Nat Neurosci 16:130–138
DeCoteau WE, Kesner RP (2000) A double dissociation between the rat hippocampus and medial caudoputamen in processing two forms of knowledge. Behav Neurosci 114:1096–1108
Devito LM, Eichenbaum H (2011) Memory for the order of events in specific sequences: contributions of the hippocampus and medial prefrontal cortex. J Neurosci 31:3169–3175
Downes JJ, Mayes AR, MacDonald C, Hunkin NM (2002) Temporal order memory in patients with Korsakoff’s syndrome and medial temporal amnesia. Neuropsychologia 40:853–861
Dragoi G, Buzsaki G (2006) Temporal coding of place sequences by hippocampal cell assemblies. Neuron 50:145–157
Dragoi G, Tonegawa S (2011) Preplay of future place cell sequences by hippocampal cellular assemblies. Nature 469:397–401
Eichenbaum H (2004) Hippocampus: cognitive processes and neural representations that underlie declarative memory. Neuron 44:109–120
Eichenbaum H, Cohen NJ (2001) From conditioning to conscious recollection: memory systems of the brain. Oxford University Press, Oxford
Eichenbaum H, Stewart C, Morris RGM (1990) Hippocampal representation in place learning. J Neurosci 10:3531–3542
Eichenbaum H, Dudchencko P, Wood E, Shapiro M, Tanila H (1999) The hippocampus, memory, and place cells: is it spatial memory or a memory space? Neuron 23:209–226
Ekstrom AD, Bookheimer SY (2007) Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain. Learn Mem 14:645–654
Ekstrom AD, Meltzer J, McNaughton BL, Barnes CA (2001) NMDA receptor antagonism blocks experience-dependent expansion of hippocampal “place fields”. Neuron 31:631–638
Ekstrom AD, Kahana MJ, Caplan JB, Fields TA, Isham EA, Newman E, Fried I (2003) Cellular networks underlying human spatial navigation. Nature 425:184–187
Ergorul C, Eichenbaum H (2004) The hippocampus and memory for “what,” “where,” and “when”. Learn Mem 11:397–405
Ergorul C, Eichenbaum H (2006) Essential role of the hippocampal formation in rapid learning of higher-order sequential associations. J Neurosci 26:4111–4117
Etienne AS, Jeffery KJ (2004) Path integration in mammals. Hippocampus 14:180–192
Farovik A, Dupont LM, Eichenbaum H (2010) Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events. Learn Mem 17:12–17
Ferbinteanu J, Shapiro ML (2003) Prospective and retrospective memory coding in the hippocampus. Neuron 40:1227–1239
Fortin NJ, Agster KL, Eichenbaum H (2002) Critical role of the hippocampus in memory for sequences of events. Nat Neurosci 5:458–462
Fouquet C, Tobin C, Rondi-Reig L (2010) A new approach for modeling episodic memory from rodents to humans: the temporal order memory. Behav Brain Res 215:172–179
Frank LM, Brown EN, Wilson M (2000) Trajectory encoding in the hippocampus and entorhinal cortex. Neuron 27:169–178
Fyhn M, Molden S, Witter MP, Moser EI, Moser M-B (2004) Spatial representation in the entorhinal cortex. Science 305:1258–1264
Gelbard-Sagiv H, Mukamel R, Harel M, Malach R, Fried I (2008) Internally generated reactivation of single neurons in human hippocampus during free recall. Science 322:96–101
Gilbert PE, Kesner RP (2002) Role of the rodent hippocampus in paired-associate learning involving associations between a stimulus and a spatial location. Behav Neurosci 116:63–71
Gill PR, Mizumori SJ, Smith DM (2011) Hippocampal episode fields develop with learning. Hippocampus 21:1240–1249
Ginther MR et al (2011) Hippocampal neurons encode different episodes in an overlapping sequence of odors task. J Neurosci 31:2706–2711
Gothard KM, Skaggs WE, McNaughton BL (1996) Dynamics of mismatch correction in the hippocampal ensemble code for space: interaction between path integration and environmental cues. J Neurosci 16:8027–8040
Hafting T, Fyhn M, Molden S, Moser M-B, Moser EI (2005) Microstructure of a spatial map in the entorhinal cortex. Nature 436:801–806
Honey RC, Watt A, Good M (1998) Hippocampal lesions disrupt an associative mismatch process. J Neurosci 18:2226–2230
Howard MW, Fotedar MS, Datey AV, Hasselmo ME (2005) The temporal context model in spatial navigation and relational learning: toward a common explanation of medial temporal lobe function across domains. Psychol Rev 112:75–116
Itskov V, Curto C, Pastalkova E, Buzsáki G (2011a) Cell assembly sequences arising from spike threshold adaptation keep track of time in the hippocampus. J Neurosci 31:2828–2834
Itskov PM, Vinnik E, Diamond ME (2011b) Hippocampal representation of touch-guided behavior in rats: persistent and independent traces of stimulus and reward location. PLoS One 1:e16462
Itskov PM, Vinnik E, Honey C, Schnupp J, Diamond ME (2012) Sound sensitivity of neurons in rat hippocampus during performance of a sound-guided task. J Neurophysiol 107:1822–1834
Jadhav SP, Frank LM (2014) Memory replay in the hippocampus. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, Heidelberg
Jadhav SP, Kemere C, German PW, Frank LM (2012) Awake hippocampal sharp-wave ripples support spatial memory. Science 336:1454–1458
Jenkins LJ, Ranaganath C (2010) Prefrontal and medial temporal lobe activity at encoding predicts temporal context memory. J Neurosci 30:15558–15565
Jensen O, Lisman JE (2005) Hippocampal sequence-encoding driven by a cortical multi-item working memory buffer. Trends Neurosci 28:67–72
Ji D, Wilson MA (2007) Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci 10:100–107
Johnson A, Redish AD (2007) Neural ensembles in CA3 transiently encode paths forward of the animal at a decision point. J Neurosci 27:12176–12189
Karlsson MP, Frank LM (2009) Awake replay of remote experiences in the hippocampus. Nat Neurosci 12:913–918
Kennedy PJ, Shapiro ML (2009) Motivational states activate distinct hippocampal representations to guide goal-directed behaviors. Proc Natl Acad Sci 106:10805–10810
Kesner RP, Gilbert PE, Barua LA (2002) The role of the hippocampus in memory for the temporal order of a sequence of odors. Behav Neurosci 116:286–290
Kesner RP, Hunsaker MR, Gilbert PE (2005) The role of CA1 in the acquisition of an object-trace-odor paired associate task. Behav Neurosci 119:781–786
Komorowski RW, Manns JR, Eichenbaum H (2009) Robust conjunctive item-place coding by hippocampal neurons parallels learning what happens. J Neurosci 29:9918–9929
Kraus B, Robinson RJ III, White JA, Eichenbaum H, Hasselmo ME (2013) Hippocampal “time cells”: time versus path integration. Neuron 78:1090–1101
Kumaran D, Maguire EA (2006a) An unexpected sequence of events: mismatch detection in the human hippocampus. PLoS Biol 4(12):e424
Kumaran D, Maguire EA (2006b) The dynamics of hippocampal activation during encoding of overlapping sequences. Neuron 49:617–629
Lehn H, Steffenach HA, van Strien NM, Veltman DJ, Witter MP, Håberg AK (2009) A specific role of the human hippocampus in recall of temporal sequences. J Neurosci 29:3475–3484
Lenck-Santini P-P, Fenton AA, Muller RU (2008) Discharge properties of hippocampal neurons during performance of a jump avoidance task. J Neurosci 28:6773–6786
Leutgeb S, Leutgeb JK, Barnes CA, Moser EI, McNaughton BL, Moser MB (2005) Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science 309:619–623
Levy WB (1989) A Computational approach to hippocampal function. In: Hawkins RD, Bowers GH (eds) Computational models of learning in simple neural systems. Academic, New York, NY, pp 243–305
Levy WB (1996) A sequence predicting CA3 is a flexible associator that learns and uses context to solve hippocampal-like tasks. Hippocampus 6:579–590
Levy WB, Xiangbau W, Baxter RA (1995) Unification of hippocampal function via computational/encoding considerations. Int J Neural Syst 6:71–80
Lisman JE (1999) Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interactions. Neuron 22:233–242
MacDonald CJ, Lepage KQ, Eden UT, Eichenbaum H (2011) Hippocampal “time cells” bridge the gap in memory for discontiguous events. Neuron 71:737–749
MacDonald CJ, Place R, Carrow S, Eichenbaum H (2013) Distinct hippocampal time cell sequences represent odor memories in head-fixed rats. J Neurosci 33:14607–14616
Maguire EA (2001) Neuroimaging studies of autobiographical event memory. Philos Trans R Soc Lond B Biol Sci 356:1441–1451
Maguire EA, Mummery CJ (1999) Differential modulation of a common memory retrieval network revealed by positron emission tomography. Hippocampus 9:54–61
Maguire EA, Frackowiak RS, Frith CD (1997) Recalling routes around London: activation of the right hippocampus in taxi drivers. J Neurosci 17:7103–7110
Mankin EA, Sparks FT, Slayyeh B, Sutherland RJ, Leutgeb S, Leutgeb JK (2012) Neuronal code for extended time in the hippocampus. Proc Natl Acad Sci USA 109:19462–19467. doi:10.1073/pnas.1214107109
Manns J, Eichenbaum H (2009) A cognitive map for object memory in the hippocampus. Learn Mem 16:616–624
Manns JR, Howard MW, Eichenbaum H (2007) Gradual changes in hippocampal activity support remembering the order of events. Neuron 56:530–540
Markus EJ, Qin Y-L, Leonard B, Skaggs WE, McNaughton BL, Barnes CA (1995) Interactions between location and task affect the spatial and directional firing of hippocampal neurons. J Neurosci 15:7079–7094
Mauk MD, Buonomano DV (2004) The neural basis of temporal processing. Annu Rev Neurosci 27:307–340
Mayes AR, Isaac CL, Holdstock JS, Hunkin NM, Montaldi D, Downes JJ, Macdonald C, Cezayirli E, Roberts JN (2001) Memory for single items, word pairs, and temporal order of different kinds in a patient with selective hippocampal lesions. Cogn Neuropsychol 18:97–123
McDonough L, Mandler JM, McKee RD, Squire LR (1995) The deferred imitation task as a nonverbal measure of declarative memory. Proc Natl Acad Sci USA 92:7580–7584
McNaughton BL, Barnes CA, Gerrard JL, Gothard K, Jung MW, Knierim JJ, Kudrimoti H, Qin Y, Skaggs WE, Suster M, Weaver KL (1996) Deciphering the hippocampal polyglot: the hippocampus as a path integration system. J Exp Biol 199:173–185
McNaughton BL, Battaglia FP, Jensen O, Moser EI, Moser MB (2006) Path integration and the neural basis of the ‘cognitive map’. Nat Rev Neurosci 7:663–678
Mehta MR, Barnes CA, McNaughton BL (1997) Experience-dependent, asymmetric expansion of hippocampal place fields. Proc Natl Acad Sci USA 94:8918–8921
Mehta MR, Quirk MC, Wilson MA (2000) Experience-dependent asymmetric shape of hippocampal receptive fields. Neuron 25:707–715
Moita MAP, Moisis S, Zhou Y, LeDoux JE, Blair HT (2003) Hippocampal place cells acquire location specific location specific responses to the conditioned stimulus during auditory fear conditioning. Neuron 37:485–497
Morris RGM, Garrud P, Rawlins JP, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683
Mumby DG (2002) Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats. Behav Brain Res 127:159–181
Muzzio IA, Levita L, Kulkarni J, Monacoi J, Kentros C, Stead M, Abbott LF, Kandel ER (2009) Attention enhances the retrieval and stability of visuospatial and olfactory representations in the dorsal hippocampus. PLoS One 7:e1000140
Naya Y, Suzuki WA (2011) Integrating what and when across the primate medial temporal lobe. Science 333:773–776
O’Keefe J, Conway DH (1980) On the trail of the hippocampal engram. Physiol Psychol 8:229–238
O’Keefe J, Nadel L (1978) The hippocampus as a cognitive map. Oxford University Press, New York, NY
Olton DS (1986) Hippocampal function and memory for temporal context. In: Isaacson RL, Pribram KH (eds) The hippocampus, vol 4. Plenum, New York, NY
Olton DS, Becker JT, Handlemann GE (1979) Hippocampus, space, and memory. Brain Behav Sci 2:313–365
Pastalkova E, Itskov V, Amarasingham A, Buzsáki G (2008) Internally generated cell assembly sequences in the rat hippocampus. Science 321:1322–1327
Paz R, Gelbard-Sagiv H, Mukamel R, Harel M, Malach R, Fried I (2010) A neural substrate in the human hippocampus for linking successive events. Proc Natl Acad Sci USA 107:6046–6051
Rawlins JNP (1985) Associations across time: the hippocampus as a temporary memory store. Behav Brain Sci 8:479–496
Redish AD, Rosenzweig ES, Bohanick JD, McNaughton BL, Barnes CA (2000) Dynamics of hippocampal ensemble activity realignment: time versus space. J Neurosci 20:9298–9309
Rekkas PV, Westerveld M, Skudlarski P, Zumer J, Pugh K, Spencer DD, Constable RT (2005) Neural correlates of temporal-order judgments versus those of spatial-location: deactivation of hippocampus may facilitate spatial performance. Brain Cogn 59:103–113
Rolls ET (2010) A computational theory of episodic memory formation in the hippocampus. Behav Brain Res 215:180–196
Ross RS, Brown TI, Stern CE (2009) The retrieval of learned sequences engages the hippocampus: evidence from fMRI. Hippocampus 19:790–799
Schendan HE, Searl MM, Melrose RJ, Stern CE (2003) An FMRI study of the role of the medial temporal lobe in implicit and explicit sequence learning. Neuron 37:1013–1025
Shapiro ML, Kennedy PJ, Ferbinteanu J (2006) Representing episodes in the mammalian brain. Curr Opin Neurobiol 16:701–709
Shimamura AP (1990) Memory for the temporal order of events in patients with frontal lobe lesions and amnesic patients. Neuropsychologia 28:803–813
Sinden JD, Rawlins JNP, Gray JA, Jarrard LE (1986) Selective cytotoxic lesions of the hippocampal formation and DRL performance in rats. Behav Neurosci 100:320–329
Skaggs WE, McNaughton BL (1996) Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science 271:1870–1873
Skaggs WE, McNaughton BL (1998) Spatial firing properties of hippocampal CA1 populations in an environment containing two visually identical regions. J Neurosci 18:8455–8466
Solomon PR, Vander Schaaf ER, Thompson RF, Weisz DJ (1986) Hippocampus and trace conditioning of the rabbit’s classically conditioned nictitating membrane response. Behav Neurosci 100:729–744
Spiers HJ, Burgess N, Hartley T, Vargha-Khadem F, O’Keefe J (2001) Bilateral hippocampal pathology impairs topographical and episodic memory but not visual pattern matching. Hippocampus 11:715–725
Staresina BP, Davachi L (2006) Differential encoding mechanisms for subsequent associative recognition and free recall. J Neurosci 26:9162–9172
Templer VL, Hampton RR (2012) Cognitive mechanisms of memory for order in rhesus monkeys. Hippocampus 23:193–201. doi:10.1002/hipo.22082
Tubridy S, Davachi L (2011) Medial temporal lobe contributions to episodic sequence encoding. Cereb Cortex 21:272–280
Tulving E (1972) Episodic and semantic memory. In: Tulving E, Donaldson W (eds) Organization of memory. Academic, New York, NY, pp 381–403
Tulving E (1984) Précis of elements of episodic memory. Behav Brain Sci 7:223–268
Vargha-Khadem F, Gadian DG, Watkins KE, Connelly A, Van Paesschen W, Mishkin M (1997) Differential effects of early hippocampal pathology on episodic and semantic memory. Science 277:376–380
Wallenstein GV, Eichenbaum H, Hasselmo ME (1998) The hippocampus as an associator of discontiguous events. Trends Neurosci 21:317–323
Wearden JH (2013) The cognitive neuroscience of time perception: how psychological studies might help to dissect the timing system. Neuropsychologia 51:187–190
Witter MP, Amaral DG (1991) Entorhinal cortex of the monkey: V projections to the dentate gyrus, hippocampus, and subicular complex. J Comput Neurol 307:437–459
Wood ER, Dudchenko PA, Robitsek RJ, Eichenbaum H (2000) Hippocampal neurons encode information about different types of memory episodes occurring in the same location. Neuron 27:623–633
Yin B, Troger AB (2011) Exploring the 4th dimension: hippocampus, time, and memory revisited. Front Integr Neurosci 5:36. doi:10.3389/fint.2011.00036
Ziv Y, Burns LD, Cocker ED, Hamel EO, Ghosh KK, Kitch LJ, Gamal AE, Scnitzer MJ (2013) Long term dynamics of CA1 hippocampal place codes. Nat Neurosci 16:264–266
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This work was supported by NIMH grant MH095297.
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Eichenbaum, H., MacDonald, C.J., Kraus, B.J. (2014). Time and the Hippocampus. In: Derdikman, D., Knierim, J. (eds) Space,Time and Memory in the Hippocampal Formation. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1292-2_11
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