Skip to main content Accessibility help
Hostname: page-component-77c89778f8-m8s7h Total loading time: 0 Render date: 2024-07-18T08:26:54.904Z Has data issue: false hasContentIssue false

22 - The paradoxical hippocampus: when forgetting helps learning

Published online by Cambridge University Press:  05 December 2011

Howard Eichenbaum
University, Center for Memory and Brain
Narinder Kapur
University College London
Alvaro Pascual-Leone
Harvard Medical School
Vilayanur Ramachandran
University of California, San Diego
Jonathan Cole
University of Bournemouth
Sergio Della Sala
University of Edinburgh
Tom Manly
MRC Cognition and Brain Sciences Unit
Andrew Mayes
University of Manchester
Oliver Sacks
Columbia University Medical Center
Get access



It is well established that the hippocampal region is critical to declarative and relational memory. Therefore, it is reasonable to expect that damage to the hippocampal region would cause impairment on any test that requires some feature of declarative/relational memory, and that on any other test, hippocampal damage is expected to have no effect. However, there have been several reports of paradoxical facilitation of learning and memory following hippocampal damage. Here, several examples in the study of animal learning and memory are discussed. In some experiments, hippocampal region damage results in the facilitation of learning simple stimulus–reward–response associations. In other experiments, the ‘flexibility’ of memory, exhibited in reversal learning and in learning multiple partially contradictory choice problems, is also facilitated following hippocampal damage. In yet other experiments, recognition based on the familiarity of stimulus combinations is improved following hippocampal damage. Each of these cases of paradoxical facilitation of learning and memory informs us about the distinctions between hippocampal-dependent memory processing and memory processes supported by other brain areas or systems. Furthermore, these findings show that competition between these systems can result in slower learning when the hippocampus is engaged, compared to when its contribution is removed.


In the field of human memory research, our understanding of how the brain supports memory began with neuropsychological studies of patients with pervasive, ‘global’ amnesia.

The Paradoxical Brain , pp. 379 - 396
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Ayalon, L., Doron, L., Weiner, I., & Joel, D. (2004). Amelioration of behavioural deficits in a rat model of Huntington's Disease by an excitotoxic lesion to the globus pallidus. Experimental Neurology, 186: 46–58.CrossRefGoogle Scholar
Bernabeau, R., Thiriet, N., Zwiller, J., & DiScala, G. (2006). Lesions of the lateral entorhinal cortex amplifies odour induced expression of c-fos, junB, and zif268 mRNA in rat brain. Synapse, 59: 135–43.CrossRefGoogle Scholar
Birrell, J. M., & Brown, V. J. (2000). Medial prefrontal cortex mediates perceptual attentional set shifting in the rat. Journal of Neuroscience, 20: 4320–4.CrossRefGoogle ScholarPubMed
Bowles, B., Crupi, C., Mirsattari, S. M., et al. (2007). Impaired familiarity with preserved recollection after anterior temporal lobe resection that spares the hippocampus. Proceedings of the National Academy of Sciences USA, 104: 16,382–7.CrossRefGoogle ScholarPubMed
Bussey, T. J., Muir, J. L., & Aggleton, J. P. (1999). Functionally dissociating aspects of event memory: the effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat. Journal of Neuroscience, 19: 495–502.CrossRefGoogle ScholarPubMed
Bussey, T. J., Warburton, E., Aggleton, J. P., & Muir, J. L. (1998). Fornix lesions can facilitate acquisition of the transverse patterning task: and challenge for ‘configural’ theories of hippocampal function. Journal of Neuroscience, 18: 1622–31.CrossRefGoogle ScholarPubMed
Cohen, N. J., & Squire, L. R. (1980). Preserved learning and retention of a pattern-analyzing skill in amnesia: dissociation of knowing how and knowing that. Science, 210: 207–10.CrossRefGoogle ScholarPubMed
Corkin, S. (1984). Lasting consequences of bilateral medial temporal lobectomy: clinical course and experimental findings in H.M. Seminars in Neurology, 4: 249–59.CrossRefGoogle Scholar
Eichenbaum, H., & Cohen, N. J. (2001). From Conditioning to Conscious Recollection: Memory Systems of the Brain. New York, NY: Oxford University Press.Google Scholar
Eichenbaum, H., Fagan, A., & Cohen, N. J. (1986). Normal olfactory discrimination learning set and facilitation of reversal learning after medial temporal damage in rats: implications for preserved learning in amnesia. Journal of Neuroscience, 6: 1876–84.CrossRefGoogle ScholarPubMed
Eichenbaum, H., Fagan, A., Mathews, P., & Cohen, N. J. (1988). Hippocampal system dysfunction and odour discrimination learning in rats: mpairment or facilitation depending on representational demands. Behavioral Neuroscience, 102: 331–9.CrossRefGoogle ScholarPubMed
Eichenbaum, H., Matthews, P., & Cohen, N. J. (1989). Further studies of hippocampal representation during odour discrimination learning. Behavioral Neuroscience, 103: 1207–16.CrossRefGoogle Scholar
Ergorul, C., & Eichenbaum, H. (2004). The hippocampus and memory for ‘What’, ‘When’, and ‘Where’. Learning and Memory, 11: 397–405.CrossRefGoogle Scholar
Fortin, N. J., Wright, S. P., & Eichenbaum, H. (2004). Recollection-like memory retrieval in rats is dependent on the hippocampus. Nature, 431: 188–91.CrossRefGoogle ScholarPubMed
Gaskin, S., & White, N. (2006). Coopertion and competition between the dorsal hippocampus and lateral amygdala in spatial discrimination learning. Hippocampus, 16: 577–85.CrossRefGoogle Scholar
Glick, S., & Greenstein, S. (1972). Facilitation of recovery after lateral hypothalamic damage by prior ablation of frontal cortex. Nature New Biology, 239: 187–8.CrossRefGoogle ScholarPubMed
Han, J. S., Gallagher, M., & Holland, P. (1998). Hippocampal lesions enhance configural learning by reducing proactive interference. Hippocampus, 8: 138–46.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Hirsh, R. (1974). The hippocampus and contextual retrieval of information from memory: a theory. Behavioral Biology, 12: 421–44.CrossRefGoogle ScholarPubMed
Laurent-Demir, C., & Jaffard, R. (2000). Paradoxical facilitatory effect of fornix lesions on acquisition of contextual fear conditioning in mice. Behavioural Brain Research, 107: 85–91.CrossRefGoogle ScholarPubMed
Mumby, D., Wood, E., Duva, C., Kornecook, T., Pinel, J., & Phillips, A. (1996). Ischemia-induced object-recognition deficits in rats are attenuated by hippocampal ablation before or soon after ischemia. Behavioral Neuroscience, 110: 266–81.CrossRefGoogle ScholarPubMed
O'Keefe, J., & Nadel, L. (1978). The Hippocampus as a Cognitive Map. New York, NY: Oxford University Press.Google Scholar
Olton, D. S., Becker, J. T., & Handlemann, G. E. (1979). Hippocampus, space, and memory. Brain and Behavioral Sciences, 2: 313–65.CrossRefGoogle Scholar
Otto, T., Schottler, F., Staubli, U., Eichenbaum, H., & Lynch, G. (1991). Hippocampus and olfactory discrimination learning: effects of entorhinal cortex lesions on olfactory learning and memory in a successive-cue, go/no-go task. Behavioral Neuroscience, 105: 111–19.CrossRefGoogle Scholar
Packard, M. G., & McGaugh, J. L. (1996). Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning. Neurobiology of Learning and Memory, 65: 65–72.CrossRefGoogle ScholarPubMed
Packard, M. G., Hirsh, R., & White, N. M. (1989). Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: Evidence for multiple memory systems. The Journal of Neuroscience, 9: 1465–72.CrossRefGoogle ScholarPubMed
Parks, C. M., & Yonelinas, A. P. (2007). Moving beyond pure signal-detection models: comment on Wixted (2007). Psychological Reviews, 114: 188–202.CrossRefGoogle Scholar
Plamondon, H., Davignon, G., Khan, S., & Charron, C. (2008). Cerebral ischemic preconditioning induces lasting effects on CA1 neuronal survival, prevents memory impairments but not ischemia-induced hyperactivity. Behavioral Brain Research, 189: 145–51.CrossRefGoogle Scholar
Poldrack, R., & Packard, M. (2003). Competition among multiple memory systems: converging evidence from animal and human brain studies. Neuropsychologia, 41: 245–51.CrossRefGoogle ScholarPubMed
Poldrack, R., & Rodreiguez, P. (2004). How do memory systems interact? Evidence from human classification learning. Neurobiology of Learning and Memory, 82: 324–32.CrossRefGoogle ScholarPubMed
Quamme, J. R., Yonelinas, A. P., & Norman, K. A. (2007). The effect of unitization on associative recognition in amnesia. Hippocampus, 17: 192–200.CrossRefGoogle ScholarPubMed
Raber, J., Villasana, L., Rosenberg, J., Zou, Y., Huang, T., & Fike, J. (2009). Irradiation enhances hippocampus-dependent cognition in mice deficient in extracellular superoxide dismutase. Hippocampus, [Epub ahead of print].Google Scholar
Rawashdeh, P., Borsetti, N., Roman, G., & Cahill, G. (2007). Melatonin suppresses nighttime memory formation in zebrafish. Science, 318: 1144–6.CrossRefGoogle ScholarPubMed
Saksida, L. M., Bussey, T. J., Buckmaster, C. A., & Murray, E. A. (2007). Impairment and facilitation of transverse patterning after lesions of the perirhinal cortex and hippocampus, respectively. Cerebral Cortex, 17: 108–15.CrossRefGoogle Scholar
Saxe, M. D., Malleret, G., Vronskaya, S., et al. (2007). Paradoxical influence of hippocampal neurogenesis on working memory. Proceedings of the National Academy of Sciences, 104: 4642–6.CrossRefGoogle ScholarPubMed
Stalnaker, T., Franz, T., Singh, T., & Schoenbaum, G. (2007). Basolateral amygdala lesions abolish orbitofrontal-dependent reversal impairments. Neuron, 54: 51–8.CrossRefGoogle ScholarPubMed
Sauvage, M. M., Fortin, N. J., Owens, C. B., Yonelinas, A. P., & Eichenbaum, H. (2008). Recognition memory: opposite effects of hippocampal damage on recollection and familiarity. Nature Neuroscience, 11: 16–18.CrossRefGoogle ScholarPubMed
Schroeder, J., Wingard, J. C., & Packard, M. G. (2002). Post-training reversible inactivation of hippocampus reveals interference between memory systems. Hippocampus, 12: 280–4.CrossRefGoogle ScholarPubMed
Scoville, W. B., & Milner, B. (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery and Psychiatry, 20: 11–12.CrossRefGoogle ScholarPubMed
Staubli, U., Ivy, G., & Lynch, G. (1984). Hippocampal denervation causes rapid forgetting of olfactory information in rats. Proceedings of the National Academy of Science, 81: 5885–7.CrossRefGoogle ScholarPubMed
White, N. M., & McDonald, R. J. (1993). Acquisition of a spatial conditioned place preference is impaired by amygdala lesions and improved by hippocampal lesions. Behavioural Brain Research, 55: 269–81.CrossRefGoogle Scholar
White, N. M., & McDonald, R. J. (2002). Multiple parallel memory systems in the brain of the rat. Neurobiology of Learning and Memory, 77: 125–84.CrossRefGoogle ScholarPubMed
Wingard, J., & Packard, M. (2008). The amygdala and emotional modulation of competition between cognitive and habit memory. Behavioural Brain Research, 193: 126–31.CrossRefGoogle ScholarPubMed
Winters, B. D., Bartko, S. J., Saksida, L. M., & Bussey, T. J. (2007a). Scopolamine infused into perirhinal cortex improves object recognition memory by blocking the acquisition of interfering object recognition. Learning and Memory, 14: 590–6.CrossRefGoogle ScholarPubMed
Winters, B. D., Saksida, L. M., & Bussey, T. J. (2007b). Paradoxical facilitation of object recognition memory after infusion of scopolamine into perirhinal cortex: implications of cholinergic system function. Journal of Neuroscience, 26: 9520–6.CrossRefGoogle Scholar
Wirth, S., Ferry, B., & DiScala, G. (1998). Facilitation of olfactory recognition by lateral entorhinal cortex lesions in rats. Behavioural Brain Research, 91: 49–59.CrossRefGoogle Scholar
Wixted, J. T. (2007). Dual process theory and signal detection theory of recognition memory. Psychological Review, 114: 152–76.CrossRefGoogle ScholarPubMed
Yonelinas, A. P. (2001). Components of episodic memory: the contribution of recollection and familiarity. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences, 356: 1363–74.CrossRefGoogle ScholarPubMed
Zhou, S., Zhu, M., Shu, D., et al. (2009). Preferential enhancement of working memory in mice lacking adenosine A2A receptors. Brain Research, 1303: 74–83.CrossRefGoogle Scholar
Zola, S. M., & Mahut, H. (1973). Paradoxical facilitation of object reversal learning after transection of the fornix in monkeys. Neuropsychologia, 11: 271–84.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats