Müller, G. E. & Pilzecker, A. Experimentelle beiträge zur lehre vom gedächtniss (German) (J. A. Barth, Leipzig, Germany, 1900).
Lechner, H. A., Squire, L. R. & Byrne, J. H. 100 years of consolidation—remembering Müller and Pilzecker. Learn. Mem. 6, 77–87 (1999).
Thompson, R. F. In search of memory traces. Annu. Rev. Psychol. 56, 1–23 (2005).
Semon, R. Die Mneme als erhaltendes Prinzip im Wechsel des organischen Geschehens (German) (Engelmann, Leipzig, Germany, 1904).
Hebb, D. O. The Organization of Behavior: A Neuropsychological Theory (John Wiley & Sons Inc., NJ, 1949).
Reijmers, L. G., Perkins, B. L., Matsuo, N. & Mayford, M. Localization of a stable neural correlate of associative memory. Science 317, 1230–1233 (2007). This study develops the FOS–tetracycline transactivator protein (tTa) transgenic mouse line, which allows long-term tagging of neurons that are active during an experience and sets up the ability to manipulate these neurons in the future.
Tonegawa, S., Liu, X., Ramirez, S. & Redondo, R. Memory engram cells have come of age. Neuron 87, 918–931 (2015).
Josselyn, S. A., Köhler, S. & Frankland, P. W. Finding the engram. Nat. Rev. Neurosci. 16, 521–534 (2015).
Squire, L. R. Mechanisms of memory. Science 232, 1612–1619 (1986).
Ribot, T. Diseases of Memory (Appleton-Century Crofts, NY, 1882).
Milner, B. & Penfield, W. The effect of hippocampal lesions on recent memory. Trans. Am. Neurol. Assoc. 1995–1956, 42–48 (1955).
Scoville, W. B. & Milner, B. Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiatry 20, 11–21 (1957).
Beatty, W. W., Salmon, D. P., Bernstein, N. & Butters, N. Remote memory in a patient with amnesia due to hypoxia. Psychol. Med. 17, 657–665 (1987).
Salmon, D. P., Lasker, B. R., Butters, N. & Beatty, W. W. Remote memory in a patient with circumscribed amnesia. Brain Cogn. 7, 201–211 (1988).
Zola-Morgan, S., Squire, L. R. & Amaral, D. G. Lesions of the hippocampal formation but not lesions of the fornix or the mammillary nuclei produce long-lasting memory impairment in monkeys. J. Neurosci. 9, 898–913 (1989).
Zola-Morgan, S., Squire, L. R. & Amaral, D. G. Lesions of the amygdala that spare adjacent cortical regions do not impair memory or exacerbate the impairment following lesions of the hippocampal formation. J. Neurosci. 9, 1922–1936 (1989).
Squire, L. R. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol. Rev. 99, 195–231 (1992).
Lehmann, H., Lacanilao, S. & Sutherland, R. J. Complete or partial hippocampal damage produces equivalent retrograde amnesia for remote contextual fear memories. Eur. J. Neurosci. 25, 1278–1286 (2007).
Teyler, T. J. & DiScenna, P. The hippocampal memory indexing theory. Behav. Neurosci. 100, 147–154 (1986). This paper proposes that the role of the hippocampus in learning and memory is to act as an index of the cortical activity present during an experience.
Damasio, A. R. Time-locked multiregional retroactivation: a systems-level proposal for the neural substrates of recall and recognition. Cognition 33, 25–62 (1989).
Milner, P. M. A cell assembly theory of hippocampal amnesia. Neuropsychologia 27, 23–30 (1989).
Alvarez, P. & Squire, L. R. Memory consolidation and the medial temporal lobe: a simple network model. Proc. Natl Acad. Sci. USA 91, 7041–7045 (1994).
McClelland, J. L., McNaughton, B. L. & O’Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychol. Rev. 102, 419–457 (1995).
Nadel, L. & Moscovitch, M. Memory consolidation, retrograde amnesia and the hippocampal complex. Curr. Opin. Neurobiol. 7, 217–227 (1997).
Bayley, P. J., Gold, J. J., Hopkins, R. O. & Squire, L. R. The neuroanatomy of remote memory. Neuron 46, 799–810 (2005).
Winocur, G., Moscovitch, M. & Bontempi, B. Memory formation and long-term retention in humans and animals: convergence towards a transformation account of hippocampal–neocortical interactions. Neuropsychologia 48, 2339–2356 (2010).
Moscovitch, M. et al. Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory. J. Anat. 207, 35–66 (2005).
Goshen, I. et al. Dynamics of retrieval strategies for remote memories. Cell 147, 678–689 (2011).
Frankland, P. W. & Bontempi, B. The organization of recent and remote memories. Nat. Rev. Neurosci. 6, 119–130 (2005). This excellent review on systems consolidation, which was written and published during the pre-engram discovery era, highlights the importance of the prefrontal cortex for remote memory and outlines several hypotheses still to be tested, such as the top-down inhibition of the hippocampus by the mPFC during remote memory.
Frankland, P. W., O’Brien, C., Ohno, M., Kirkwood, A. & Silva, A. J. α-CaMKII-dependent plasticity in the cortex is required for permanent memory. Nature 411, 309–313 (2001).
Hayashi, M. L. et al. Altered cortical synaptic morphology and impaired memory consolidation in forebrain- specific dominant-negative PAK transgenic mice. Neuron 42, 773–787 (2004).
Bontempi, B., Laurent-Demir, C., Destrade, C. & Jaffard, R. Time-dependent reorganization of brain circuitry underlying long-term memory storage. Nature 400, 671–675 (1999).
Markowitsch, H. J. Which brain regions are critically involved in the retrieval of old episodic memory? Brain Res. Rev. 21, 117–127 (1995).
Fink, G. R. et al. Cerebral representation of one’s own past: neural networks involved in autobiographical memory. J. Neurosci. 16, 4275–4282 (1996).
Takashima, A. et al. Declarative memory consolidation in humans: a prospective functional magnetic resonance imaging study. Proc. Natl Acad. Sci. USA 103, 756–761 (2006).
Rudy, J. W., Biedenkapp, J. C. & O’Reilly, R. C. Prefrontal cortex and the organization of recent and remote memories: an alternative view. Learn. Mem. 12, 445–446 (2005).
Eichenbaum, H. Memory: organization and control. Annu. Rev. Psychol. 68, 19–45 (2017).
Takehara, K., Kawahara, S. & Kirino, Y. Time-dependent reorganization of the brain components underlying memory retention in trace eyeblink conditioning. J. Neurosci. 23, 9897–9905 (2003).
Frankland, P. W. The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 304, 881–883 (2004).
Maviel, T., Durkin, T. P., Menzaghi, F. & Bontempi, B. Sites of neocortical reorganization critical for remote spatial memory. Science 305, 96–99 (2004).
Takehara-Nishiuchi, K. Systems consolidation requires postlearning activation of NMDA receptors in the medial prefrontal cortex in trace eyeblink conditioning. J. Neurosci. 26, 5049–5058 (2006).
Teixeira, C. M., Pomedli, S. R., Maei, H. R., Kee, N. & Frankland, P. W. Involvement of the anterior cingulate cortex in the expression of remote spatial memory. J. Neurosci. 26, 7555–7564 (2006).
Lopez, J. et al. Context-dependent modulation of hippocampal and cortical recruitment during remote spatial memory retrieval. Hippocampus 22, 827–841 (2012).
Quinn, J. J., Ma, Q. D., Tinsley, M. R., Koch, C. & Fanselow, M. S. Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories. Learn. Mem. 15, 368–372 (2008).
Wang, S.-H., Tse, D. & Morris, R. G. M. Anterior cingulate cortex in schema assimilation and expression. Learn. Mem. 19, 315–318 (2012). This study builds on the findings of a previous paper from the same laboratory that created a task to study schema memory and identified a time-limited role of the hippocampus in schema learning. Here, they identify the prefrontal cortex as an important node in schema memory and schema learning.
Han, J.-H. et al. Selective erasure of a fear memory. Science 323, 1492–1496 (2009). Using a loss-of-function approach, this study demonstrates the existence of engram cells; genetic ablation of amygdala cells with high excitability resulted in the specific loss of a fear memory.
Koya, E. et al. Targeted disruption of cocaine-activated accumbens neurons prevents context-specific sensitization. Nat. Neurosci. 12, 1069–1073 (2009).
Liu, X. et al. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484, 381–385 (2012). This seminal study identified engram cells for a specific memory using a gain-offunction approach; optogenetic reactivation of hippocampal cells activated by learning results in recall of the specific memory.
Ramirez, S. et al. Creating a false memory in the hippocampus. Science 341, 387–391 (2013).
Guenthner, C. J., Miyamichi, K., Yang, H. H., Heller, H. C. & Luo, L. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations. Neuron 78, 773–784 (2013).
Denny, C. A. et al. Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron 83, 189–201 (2014).
Ryan, T. J., Roy, D. S., Pignatelli, M., Arons, A. & Tonegawa, S. Engram cells retain memory under retrograde amnesia. Science 348, 1007–1013 (2015). This study demonstrates specific enduring physical changes in engram cells following learning and demonstrates that post-encoding protein synthesis is dispensable for memory storage. This paper also provides existence of silent engram cells.
Roy, D. S. Tonegawa, S. Sara, S. J. in Learning and Memory: A Comprehensive Reference (ed. Byrne, J. H.) 637–658 (Elsevier, Amsterdam, 2017).
Roy, D. S., Muralidhar, S., Smith, L. M. & Tonegawa, S. Silent memory engrams as the basis for retrograde amnesia. Proc. Natl Acad. Sci. USA 114, E9972–E9979 (2017).
Lesburgueres, E. et al. Early tagging of cortical networks is required for the formation of enduring associative memory. Science 331, 924–928 (2011). This study shows that inhibiting plasticity in the prefrontal cortex during learning prevented the formation of remote memory, demonstrating that prefrontal cortex activity during learning is crucial for remote memory.
Kitamura, T. et al. Engrams and circuits crucial for systems consolidation of a memory. Science 356, 73–78 (2017). This study discovers that silent engrams form in the prefrontal cortex during learning and mature during systems consolidation with aid from hippocampal engram cells, whereas active engram cells form during training de-mature to silent engram cells during systems consolidation.
Sürmeli, G. et al. Molecularly defined circuitry reveals input-output segregation in deep layers of the medial entorhinal cortex. Neuron 88, 1040–1053 (2015).
Ohkawa, N. et al. Artificial association of pre-stored information to generate a qualitatively new memory. Cell Rep. 11, 261–269 (2015).
Zhao, M.-G. et al. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron 47, 859–872 (2005).
Vetere, G. et al. Spine growth in the anterior cingulate cortex is necessary for the consolidation of contextual fear memory. Proc. Natl Acad. Sci. USA 108, 8456–8460 (2011).
Ye, L. et al. Wiring and molecular features of prefrontal ensembles representing distinct experiences. Cell 165, 1776–1788 (2016).
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).
Roy, D. S. et al. Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease. Nature 531, 508–512 (2016).
Okuyama, T., Kitamura, T., Roy, D. S., Itohara, S. & Tonegawa, S. Ventral CA1 neurons store social memory. Science 353, 1536–1541 (2016).
Miller, C. A. et al. Cortical DNA methylation maintains remote memory. Nat. Neurosci. 13, 664–666 (2010).
Zovkic, I. B., Paulukaitis, B. S., Day, J. J., Etikala, D. M. & Sweatt, J. D. Histone H2A. Z subunit exchange controls consolidation of recent and remote memory. Nature 515, 582–586 (2014). This study discovers epigenetic changes in the hippocampus and prefrontal cortex during learning that are important for the formation of recent and remote memory.
Takehara-Nishiuchi, K. & McNaughton, B. L. Spontaneous changes of neocortical code for associative memory during consolidation. Science 322, 960–963 (2008). This study records from prefrontal cortex neurons during learning and consolidation and uncovers physiological correlates of systems consolidation in these neurons across time.
Ziv, Y. et al. Long-term dynamics of CA1 hippocampal place codes. Nat. Neurosci. 16, 264–266 (2013).
Nakashiba, T., Buhl, D. L., McHugh, T. J. & Tonegawa, S. Hippocampal CA3 output is crucial for ripple-associated reactivation and consolidation of memory. Neuron 62, 781–787 (2009).
Suh, J., Foster, D. J., Davoudi, H., Wilson, M. A. & Tonegawa, S. Impaired hippocampal ripple-associated replay in a mouse model of Schizophrenia. Neuron 80, 484–493 (2013).
Yamamoto, J. & Tonegawa, S. Direct medial entorhinal cortex input to hippocampal CA1 is crucial for extended quiet awake replay. Neuron 96, 217–227.e4 (2017).
Ego-Stengel, V. & Wilson, M. A. Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus 20, 1–10 (2010).
Girardeau, G., Benchenane, K., Wiener, S. I., Buzsáki, G. & Zugaro, M. B. Selective suppression of hippocampal ripples impairs spatial memory. Nat. Neurosci. 12, 1222–1223 (2009).
Maingret, N., Girardeau, G., Todorova, R., Goutierre, M. & Zugaro, M. Hippocampo-cortical coupling mediates memory consolidation during sleep. Nat. Neurosci. 19, 959–964 (2016).
Xia, F. et al. Parvalbumin-positive interneurons mediate cortical-hippocampal interactions that are necessary for memory consolidation. eLife 6, e27868 (2017).
Wheeler, A. L. et al. Identification of a functional connectome for long-term fear memory in mice. PLoS Comput. Biol. 9, e1002853 (2013).
Tayler, K. K., Tanaka, K. Z., Reijmers, L. G. & Wiltgen, B. J. Reactivation of neural ensembles during the retrieval of recent and remote memory. Curr. Biol. 23, 99–106 (2013).
Debiec, J., LeDoux, J. E. & Nader, K. Cellular and systems reconsolidation in the hippocampus. Neuron 36, 527–538 (2002).
Winocur, G., Frankland, P. W., Sekeres, M., Fogel, S. & Moscovitch, M. Changes in context-specificity during memory reconsolidation: selective effects of hippocampal lesions. Learn. Mem. 16, 722–729 (2009).
Wiltgen, B. J. & Silva, A. J. Memory for context becomes less specific with time. Learn. Mem. 14, 313–317 (2007).
Winocur, G., Moscovitch, M. & Sekeres, M. Memory consolidation or transformation: context manipulation and hippocampal representations of memory. Nat. Neurosci. 10, 555–557 (2007).
Sakurai, K. et al. Capturing and manipulating activated neuronal ensembles with CANE delineates a hypothalamic social-fear circuit. Neuron 92, 739–753 (2016).
Meltzer, L. A., Yabaluri, R. & Deisseroth, K. A role for circuit homeostasis in adult neurogenesis. Trends Neurosci. 28, 653–660 (2005).
Kitamura, T. et al. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell 139, 814–827 (2009).
Akers, K. G. et al. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344, 598–602 (2014).
Yasuda, M. et al. Multiple forms of activity-dependent competition refine hippocampal circuits in vivo. Neuron 70, 1128–1142 (2011).
Maren, S., Aharonov, G. & Fanselow, M. S. Retrograde abolition of conditional fear after excitotoxic lesions in the basolateral amygdala of rats: absence of a temporal gradient. Behav. Neurosci. 110, 718–726 (1996).
Redondo, R. L. et al. Bidirectional switch of the valence associated with a hippocampal contextual memory engram. Nature 513, 426–430 (2014).
Kim, J., Pignatelli, M., Xu, S., Itohara, S. & Tonegawa, S. Antagonistic negative and positive neurons of the basolateral amygdala. Nat. Neurosci. 19, 1636–1646 (2016).
Morrissey, M. D., Maal-Bared, G., Brady, S. & Takehara-Nishiuchi, K. Functional dissociation within the entorhinal cortex for memory retrieval of an association between temporally discontiguous stimuli. J. Neurosci. 32, 5356–5361 (2012).
Burwell, R. D., Bucci, D. J., Sanborn, M. R. & Jutras, M. J. Perirhinal and postrhinal contributions to remote memory for context. J. Neurosci. 24, 11023–11028 (2004).
Corcoran, K. A. et al. NMDA receptors in retrosplenial cortex are necessary for retrieval of recent and remote context fear memory. J. Neurosci. 31, 11655–11659 (2011).
Cowansage, K. K. et al. Direct reactivation of a coherent neocortical memory of context. Neuron 84, 432–441 (2014).
Xie, H. et al. In vivo imaging of immediate early gene expression reveals layer-specific memory traces in the mammalian brain. Proc. Natl Acad. Sci. USA 111, 2788–2793 (2014).
Zelikowsky, M., Hersman, S., Chawla, M. K., Barnes, C. A. & Fanselow, M. S. Neuronal ensembles in amygdala, hippocampus, and prefrontal cortex track differential components of contextual fear. J. Neurosci. 34, 8462–8466 (2014).
Jones, B. F. & Witter, M. P. Cingulate cortex projections to the parahippocampal region and hippocampal formation in the rat. Hippocampus 17, 957–976 (2007).
Vertes, R. P. Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51, 32–58 (2004).
Wang, S.-H., Teixeira, C. M., Wheeler, A. L. & Frankland, P. W. The precision of remote context memories does not require the hippocampus. Nat. Neurosci. 12, 253–255 (2009).
Kitamura, T. et al. Hippocampal function is not required for the precision of remote place memory. Mol. Brain 5, 5 (2012).
Wallis, J. D., Anderson, K. C. & Miller, E. K. Single neurons in prefrontal cortex encode abstract rules. Nature 411, 953–956 (2001).
Rich, E. L. & Shapiro, M. Rat prefrontal cortical neurons selectively code strategy switches. J. Neurosci. 29, 7208–7219 (2009).
Richards, B. A. et al. Patterns across multiple memories are identified over time. Nat. Neurosci. 17, 981–986 (2014).
Morrissey, M. D., Insel, N. & Takehara-Nishiuchi, K. Generalizable knowledge outweighs incidental details in prefrontal ensemble code over time. eLife 6, e22177 (2017).
Wiltgen, B. J. et al. The hippocampus plays a selective role in the retrieval of detailed contextual memories. Curr. Biol. 20, 1336–1344 (2010).
Kim, J. J. & Fanselow, M. S. Modality-specific retrograde amnesia of fear. Science 256, 675–677 (1992).
Anagnostaras, S. G., Maren, S. & Fanselow, M. S. Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination. J. Neurosci. 19, 1106–1114 (1999).
Winocur, G., Sekeres, M. J., Binns, M. A. & Moscovitch, M. Hippocampal lesions produce both nongraded and temporally graded retrograde amnesia in the same rat. Hippocampus 23, 330–341 (2013).
Sutherland, R. J., O’Brien, J. & Lehmann, H. Absence of systems consolidation of fear memories after dorsal, ventral, or complete hippocampal damage. Hippocampus 18, 710–718 (2008).
Kim, J. J., Clark, R. E. & Thompson, R. F. Hippocampectomy impairs the memory of recently, but not remotely, acquired trace eyeblink conditioned responses. Behav. Neurosci. 109, 195–203 (1995).
Quillfeldt, J. A. et al. Different brain areas are involved in memory expression at different times from training. Neurobiol. Learn. Mem. 66, 97–101 (1996).
Winocur, G. Anterograde and retrograde amnesia in rats with dorsal hippocampal or dorsomedial thalamic lesions. Behav. Brain Res. 38, 145–154 (1990).
Tse, D. et al. Schemas and memory consolidation. Science 316, 76–82 (2007).
Broadbent, N. J., Squire, L. R. & Clark, R. E. Reversible hippocampal lesions disrupt water maze performance during both recent and remote memory tests. Learn. Mem. 13, 187–191 (2006).
Clark, R. E., Broadbent, N. J. & Squire, L. R. Impaired remote spatial memory after hippocampal lesions despite extensive training beginning early in life. Hippocampus 15, 340–346 (2005).
Mumby, D. G., Astur, R. S., Weisend, M. P. & Sutherland, R. J. Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations. Behav. Brain Res. 106, 97–107 (1999).
Sutherland, R. J. et al. Retrograde amnesia after hippocampal damage: recent versus remote memories in two tasks. Hippocampus 11, 27–42 (2001).