- Email: [email protected]
Recognition Memory: An Old Idea Given New Life
Dispatch R725
strains substantially preceded the radiation of pea aphid host races onto their various plants. This pattern implies that much of the symbionts’ evolutionary history has taken place outside of pea aphid in other insect hosts. Pea aphid has likely acquired multiple strains of the symbionts from different interspecific sources. In the future, it may prove exciting to extend this work to other insect species within pea aphid’s various ecological communities. In so doing, we will gain a much fuller picture of the interspecific genetic exchange network among eukaryotes, as facilitated by secondary bacterial symbionts.
5.
6.
7.
8.
9.
10.
References 1. Ochman, H., Lawrence, J.G., and Groisman, E.A. (2000). Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304. 2. Harrison, E., and Brockhurst, M.A. (2012). Plasmid-mediated horizontal gene transfer is a coevolutionary process. Trends Microbiol. 20, 262–267. 3. Stokes, H.W., and Gillings, M.R. (2011). Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens. FEMS Microbiol. Rev. 35, 790–819. 4. Henry, L.M., Peccoud, J., Simon, J.C., Hadfield, J.D., Maiden, M.J.C., Ferrari, J., and
11.
12.
13.
Godfray, H.C.J. (2013). Horizontally transmitted symbionts and host colonization of ecological niches. Curr. Biol. 23, 1713–1717. Ferrari, J., and Vavre, F. (2011). Bacterial symbionts in insects or the story of communities affecting communities. Philos. Trans. R. Soc. B 366, 1389–1400. Oliver, K.M., Degnan, P.H., Burke, G.R., and Moran, N.A. (2010). Facultative symbionts of aphids and the horizontal transfer of ecologically important traits. Annu. Rev. Entomol. 55, 247–266. Feldhaar, H. (2011). Bacterial symbionts as mediators of ecologically important traits of insect hosts. Ecol. Entomol. 36, 533–543. White, J.A. (2011). Caught in the act: rapid, symbiont-driven evolution. Bioessays 33, 823–829. Russell, J.A., Latorre, A., Sabater-Munoz, B., Moya, A., and Moran, N.A. (2003). Side-stepping secondary symbionts: widespread horizontal transfer across and beyond the Aphidoidea. Mol. Ecol. 12, 1061–1075. Ferrari, J., Via, S., and Godfray, H.C.J. (2008). Population differentiation and genetic variation in performance on eight hosts in the pea aphid complex. Evolution 62, 2508–2524. Ferrari, J., West, J.A., Via, S., and Godfray, H.C.J. (2012). Population genetic structure and secondary symbionts in host-associated populations of the pea aphid complex. Evolution 66, 375–390. Tsuchida, T., Koga, R., and Fukatsu, T. (2004). Host plant specialization governed by facultative symbiont. Science 303, 1989–1989. Tsuchida, T., Koga, R., Matsumoto, S., and Fukatsu, T. (2011). Interspecific symbiont transfection confers a novel ecological trait to the recipient insect. Biol. Lett. 7, 245–248.
Recognition Memory: An Old Idea Given New Life A new study combining behavioral and physiological approaches has given new life to the old idea that the hippocampus is critically involved in familiarity-based recognition memory. Robert E. Clark The term ‘declarative memory’ refers to our capacity to consciously remember facts and events. This is the type of memory that one ordinarily refers to when colloquially using the word ‘memory’. For example, declarative memory is required for remembering what you had for breakfast this morning, as well as for remembering what the word ‘breakfast’ means. One of the most widely studied examples of declarative memory is recognition memory. Recognition memory is the capacity to judge that an item has been previously encountered. This type of memory is thought to consist of two components: recollection and
familiarity. Recollection involves remembering specific contextual details about a prior learning episode; familiarity involves simply knowing that an item has been presented previously without having available additional information about the learning episode. The neuroanatomy underlying these components of recognition memory has been an active topic of debate for more than a decade. One prominent view holds that recollection depends on the hippocampus, whereas familiarity depends on the adjacent perirhinal cortex [1]. Another view holds that the hippocampus and perirhinal cortex are involved in both familiarity and recollection [2]. A clear prediction of the first view is that memory tasks
14. Leonardo, T.E. (2004). Removal of a specialization-associated symbiont does not affect aphid fitness. Ecol. Lett. 7, 461–468. 15. McLean, A.H.C., van Asch, M., Ferrari, J., and Godfray, H.C.J. (2011). Effects of bacterial secondary symbionts on host plant use in pea aphids. Proc. Biol. Sci. 278, 760–766. 16. Stahlhut, J.K., Desjardins, C.A., Clark, M.E., Baldo, L., Russell, J.A., Werren, J.H., and Jaenike, J. (2010). The mushroom habitat as an ecological arena for global exchange of Wolbachia. Mol. Ecol. 19, 1940–1952. 17. Russell, J.A., Goldman-Huertas, B., Moreau, C.S., Baldo, L., Stahlhut, J.K., Werren, J.H., and Pierce, N.E. (2009). Specialization and geographic isolation among Wolbachia symbionts from ants and Lycaenid butterflies. Evolution 63, 624–640. 18. Caspi-Fluger, A., Inbar, M., Mozes-Daube, N., Katzir, N., Portnoy, V., Belausov, E., Hunter, M.S., and Zchori-Fein, E. (2012). Horizontal transmission of the insect symbiont Rickettsia is plant-mediated. Proc. Biol. Sci. 279, 1791–1796. 19. Moran, N.A., and Dunbar, H.E. (2006). Sexual acquisition of beneficial symbionts in aphids. Proc. Natl. Acad. Sci. USA 103, 12803–12806. 20. Gehrer, L., and Vorburger, C. (2012). Parasitoids as vectors of facultative bacterial endosymbionts in aphids. Biol. Lett. 8, 613–615.
Department of Entomology, University of Kentucky, Lexington, KY 40546, USA. E-mail: [email protected]
http://dx.doi.org/10.1016/j.cub.2013.07.069
requiring only familiarity-based judgments should be spared after selective hippocampal damage and impaired after damage to the perirhinal cortex. Indeed, a substantial literature involving lesions, single-unit recordings and neuroimaging is consistent with this view [3]. A compelling component of this literature is the numerous studies reporting spared familiarity-based recognition memory in animals with selective hippocampal damage or disruption [4]. In this issue of Current Biology, Cohen et al. [5] challenge this perspective by reporting in a series of eleven experiments that reversible disruption of the mouse hippocampus during memory encoding, retention or retrieval profoundly impairs performance on the novel object recognition task — a task that can be accomplished using only familiarity-based recognition memory. These findings were obtained even when potential spatial confounds were eliminated. Further, the authors found that extracellular glutamate efflux in the
Current Biology Vol 23 No 17 R726
CA 3 Mossy fibers
Schaffer collaterals
CA 1
Temporoammonic pathways
S
DG Perforant pathway II
III
IV
V
Entorhinal cortex Medial
Parahippocampal / postrhinal cortex
Lateral
Perirhinal cortex
Unimodal and polymodal association areas (frontal, temporal, and parietal lobes) Neocortex Current Biology
Figure 1. Schematic view of the primary connections of the hippocampus. The hippocampus (highlighted in red), defined here as the dentate gyrus (DG), CA3, CA1, and subiculum (S), is anatomically situated to receive highly processed information from widespread neocortical regions through three temporal cortical areas, the entorhinal, perirhinal, and parahippocampal cortices (in the rat, the term postrhinal cortex replaces the term parahippocampal cortex), as well as through other direct projections to the entorhinal cortex from areas outside the temporal lobe. The figure shows a simplified view of the way in which information enters the hippocampus from the superficial layers (II and III) of the entorhinal cortex and then flows in a largely unidirectional feed-forward direction to the deep layers of entorhinal cortex (IV and V). The medial entorhinal cortex is densely connected with the postrhinal cortex and is specialized for spatial information, while the lateral entorhinal cortex is densely connected with the perirhinal cortex and is specialized for object information. These two processing streams are primarily combined when they reach the hippocampus.
hippocampus and the firing properties of hippocampal neurons during performance of the recognition memory task are consistent with the involvement of the hippocampus in familiarity-based recognition memory. Early Insights into the Anatomy of Memory On September 1, 1953 at Hartford Hospital in Hartford Connecticut, the
neurosurgeon William Scoville excised bilaterally the medial temporal lobes of a patient with severe epilepsy. The surgery was an attempt to reduce the severity of the patient’s seizures, and in this regard the surgery was a success. The bilateral removal of the medial temporal lobes, however, also left the patient with profound amnesia. The subsequent systematic evaluation of this patient, known now as H.M.,
ushered in the modern era of memory research. Work with H.M. and with other patients with similar damage has established four fundamental principles of memory [6]. First, memory is a distinct cerebral ability, in large part separate from other cognitive functions such as perception, intelligence, personality and motivation. Second, only long-term memory is disrupted because information could be maintained and utilized for a short time in working memory. Third, medial temporal lobe structures are not the ultimate repository of long-term memory, because remote memory remained largely intact. Fourth, despite the debilitating and pervasive memory impairment, motor skills memory could still be acquired — providing the first clues that memory is not a single phenomenon [7]. At the time that H.M. was first described [8], there was some evidence to suggest the hippocampus might be the critical structure for the memory impairment. However, although the term ‘hippocampus’ was used in the title of the classic 1957 paper [8], the authors explicitly noted that the specific contributions of the hippocampus to the memory impairment must remain tentative because other structures were also damaged by the surgery, including the amygdala and cortical regions adjacent to the hippocampus and amygdala. Accordingly, efforts began almost immediately to develop an animal model of medial temporal lobe amnesia. An Animal Model of Recognition Memory Despite rapid and vigorous efforts to develop an animal model of H.M.’s amnesia, an animal model would not be achieved for more than 20 years. The primary difficulty was that, during the 1960s and 1970s, it was not yet appreciated that different learning and memory tasks could be supported by different brain systems [9]. Many of the tasks given to animals with hippocampal lesions were ones that they could learn as a skill or habit, even if humans tended to learn the task by memorizing the material. Establishing an animal model of human memory impairment would require developing tasks for animals that assessed the same kind of memory that is impaired in humans after medial temporal lobe damage [10].
Dispatch R727
The key development was the creation of a ‘one-trial’ test of recognition memory, where monkeys were first trained to select an object that was previously encountered (delayed matching-to-sample, DMS) or, in another version, select a novel object that was paired with a previously encountered object (delayed nonmatching-to-sample, DNMS). Because new objects were used on each trial, animals were prevented from solving the task gradually using habit memory. In 1978, it was reported that monkeys with lesions designed to mimic H.M.’s damage exhibited a similar memory impairment profile to H.M. when tested on the DNMS task [11]. This study signaled the successful development of an animal model of recognition memory in the monkey and led eventually to the identification of the structures comprising the medial temporal lobe memory system [12]. The model was also extended to include rodents, and in the rodents the DMS and DNMS tasks were eventually supplanted by one-trial spontaneous recognition memory tasks [13,14], similar to the one used by Cohen et al. [5] in their new work. The Anatomy of Recognition Memory The system of brain structures important for memory includes the hippocampus and the adjacent entorhinal, perirhinal and parahippocampal cortices (Figure 1). While the hippocampus was the early focus for most of the work with the animal model, it was eventually discovered that selective damage to the cortical regions adjacent to the hippocampus, particularly the perirhinal cortex, produced more profound recognition memory impairments than selective damage to the hippocampus itself (for review see [13]). As noted above, it has become common in modern
formulations to deemphasize the role of the hippocampus in familiarity-based recognition memory performance [3,4,15–17]. Thus, the new work of Cohen et al. [5] is timely and makes the important observation that the hippocampus itself appears to be critically involved in familiarity-based recognition memory. Summary One way to view the function of the hippocampus is that it sits at the end of a processing hierarchy of the medial temporal lobe, receiving input from both the perirhinal and parahippocampal cortices, largely by way of the entorhinal cortex. Guided by the anatomy, it seems reasonable that the hippocampus extends and combines functions performed by the structures that project to it. By this view, the hippocampus and other structures of the medial temporal lobe, like the perirhinal cortex, work together in a cooperative and complementary manner [18]. Finally, the work by Cohen et al. [5] and others [13,18] suggest that the anatomy of familiarity-based and recollection-based recognition memory may not be a straightforward anatomical dichotomy. To understand the substrates of recognition memory more precisely it will be important to continue to develop methods to determine how tasks are approached and to identify the critical information that is used to support performance. References 1. Brown, M.W., and Aggleton, J.P. (2001). Recognition memory: what are the roles of the perirhinal cortex and hippocampus? Nat. Rev. Neurosci. 2, 51–61. 2. Squire, L.R., Wixted, J.T., and Clark, R.E. (2007). Recognition memory and the medial temporal lobe: A new perspective. Nat. Rev. Neurosci. 8, 872–883. 3. Eichenbaum, H., Yonelinas, A.R., and Ranganath, C. (2007). The medial temporal lobe and recognition memory. Annu. Rev. Neurosci. 30, 123–152. 4. Winters, B.D., Saksida, L.M., and Bussey, T.J. (2008). Object recognition memory: neurobiological mechanisms of encoding,
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consolidation and retrieval. Neurosci. Biobehav. Rev. 32, 1055–10570. Cohen, S.J., Munchow, A.H., Rios, L.M., Zhang, G., A´sgeirsdo´ttir, H.N., and Stackman, R.W. (2013). The rodent hippocampus is essential for nonspatial object memory. Curr. Biol. 23, 1685–1690. Squire, L.R., and Wixted, J.T. (2011). The cognitive neuroscience of human memory since H.M. Annu. Rev. Neurosci. 34, 259–288. Milner, B. (2005). The medial temporal-lobe amnesic syndrome. Psychiatr. Clin. N. Am. 28, 599–611. Scoville, W.B., and Milner, B. (1957). Loss of recentmemoryafter bilateral hippocampal lesions. J. Neurol. Neurosurg. Psych. 20, 11–21. Squire, L.R. (2004). Memory systems of the brain: a brief history and current perspective. Neurobiol. Learn. Mem. 82, 171–177. Gaffan, D. (1974). Recognition impaired and association intact in the memory of monkeys after transaction of the fornix. J. Comp. Physiol. Psychol. 88, 1100–1109. Mishkin, M. (1978). Memory in monkeys severely impaired by combined but not by separate removal of amygdala and hippocampus. Nature 273, 297–298. Squire, L.R., and Zola-Morgan, S. (1991). The medial temporal lobe memory system. Science 253, 1380–1386. Clark, R.E., and Squire, L.R. (2010). An animal model of recognition memory and medial temporal lobe amnesia: history and current issues. Neuropsychologia 48, 2234–2244. Clark, R.E., and Squire, L.R. (2013). Similarity in form and function of the hippocampus in rodents, monkeys, and humans. Proc. Natl. Acad. Sci. USA 110(Suppl 2 ), 10365–10370. Winters, B.D., Saksida, L.M., and Bussey, T.J. (2010). Implications of animal object memory research for human amnesia. Neuropsychologia 48, 2251–2261. Eichenbaum, H., Sauvage, M., Fortin, N., Komorowski, R., and Lipton, P. (2012). Towards a functional organization of episodic memory in the medial temporal lobe. Neurosci. Biobehav. Rev. 36, 1597–1608. Brown, M.W., Warburton, E.C., and Aggleton, J.P. (2010). Recognition memory: material, processes, and substrates. Hippocampus 20, 1228–1244. Wixted, J.T., and Squire, L.R. (2011). The familiarity/recollection distinction does not illuminate medial temporal lobe function: response to Montaldi and Mayes. Trends Cogn. Sci. 8, 340–341.
Veterans Affairs Medical Center, San Diego, CA 92161 and University of California, San Diego, School of Medicine, 9500 Gilman, La Jolla, CA 92093, USA. E-mail: [email protected]
http://dx.doi.org/10.1016/j.cub.2013.07.037
strains substantially preceded the radiation of pea aphid host races onto their various plants. This pattern implies that much of the symbionts’ evolutionary history has taken place outside of pea aphid in other insect hosts. Pea aphid has likely acquired multiple strains of the symbionts from different interspecific sources. In the future, it may prove exciting to extend this work to other insect species within pea aphid’s various ecological communities. In so doing, we will gain a much fuller picture of the interspecific genetic exchange network among eukaryotes, as facilitated by secondary bacterial symbionts.
5.
6.
7.
8.
9.
10.
References 1. Ochman, H., Lawrence, J.G., and Groisman, E.A. (2000). Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304. 2. Harrison, E., and Brockhurst, M.A. (2012). Plasmid-mediated horizontal gene transfer is a coevolutionary process. Trends Microbiol. 20, 262–267. 3. Stokes, H.W., and Gillings, M.R. (2011). Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens. FEMS Microbiol. Rev. 35, 790–819. 4. Henry, L.M., Peccoud, J., Simon, J.C., Hadfield, J.D., Maiden, M.J.C., Ferrari, J., and
11.
12.
13.
Godfray, H.C.J. (2013). Horizontally transmitted symbionts and host colonization of ecological niches. Curr. Biol. 23, 1713–1717. Ferrari, J., and Vavre, F. (2011). Bacterial symbionts in insects or the story of communities affecting communities. Philos. Trans. R. Soc. B 366, 1389–1400. Oliver, K.M., Degnan, P.H., Burke, G.R., and Moran, N.A. (2010). Facultative symbionts of aphids and the horizontal transfer of ecologically important traits. Annu. Rev. Entomol. 55, 247–266. Feldhaar, H. (2011). Bacterial symbionts as mediators of ecologically important traits of insect hosts. Ecol. Entomol. 36, 533–543. White, J.A. (2011). Caught in the act: rapid, symbiont-driven evolution. Bioessays 33, 823–829. Russell, J.A., Latorre, A., Sabater-Munoz, B., Moya, A., and Moran, N.A. (2003). Side-stepping secondary symbionts: widespread horizontal transfer across and beyond the Aphidoidea. Mol. Ecol. 12, 1061–1075. Ferrari, J., Via, S., and Godfray, H.C.J. (2008). Population differentiation and genetic variation in performance on eight hosts in the pea aphid complex. Evolution 62, 2508–2524. Ferrari, J., West, J.A., Via, S., and Godfray, H.C.J. (2012). Population genetic structure and secondary symbionts in host-associated populations of the pea aphid complex. Evolution 66, 375–390. Tsuchida, T., Koga, R., and Fukatsu, T. (2004). Host plant specialization governed by facultative symbiont. Science 303, 1989–1989. Tsuchida, T., Koga, R., Matsumoto, S., and Fukatsu, T. (2011). Interspecific symbiont transfection confers a novel ecological trait to the recipient insect. Biol. Lett. 7, 245–248.
Recognition Memory: An Old Idea Given New Life A new study combining behavioral and physiological approaches has given new life to the old idea that the hippocampus is critically involved in familiarity-based recognition memory. Robert E. Clark The term ‘declarative memory’ refers to our capacity to consciously remember facts and events. This is the type of memory that one ordinarily refers to when colloquially using the word ‘memory’. For example, declarative memory is required for remembering what you had for breakfast this morning, as well as for remembering what the word ‘breakfast’ means. One of the most widely studied examples of declarative memory is recognition memory. Recognition memory is the capacity to judge that an item has been previously encountered. This type of memory is thought to consist of two components: recollection and
familiarity. Recollection involves remembering specific contextual details about a prior learning episode; familiarity involves simply knowing that an item has been presented previously without having available additional information about the learning episode. The neuroanatomy underlying these components of recognition memory has been an active topic of debate for more than a decade. One prominent view holds that recollection depends on the hippocampus, whereas familiarity depends on the adjacent perirhinal cortex [1]. Another view holds that the hippocampus and perirhinal cortex are involved in both familiarity and recollection [2]. A clear prediction of the first view is that memory tasks
14. Leonardo, T.E. (2004). Removal of a specialization-associated symbiont does not affect aphid fitness. Ecol. Lett. 7, 461–468. 15. McLean, A.H.C., van Asch, M., Ferrari, J., and Godfray, H.C.J. (2011). Effects of bacterial secondary symbionts on host plant use in pea aphids. Proc. Biol. Sci. 278, 760–766. 16. Stahlhut, J.K., Desjardins, C.A., Clark, M.E., Baldo, L., Russell, J.A., Werren, J.H., and Jaenike, J. (2010). The mushroom habitat as an ecological arena for global exchange of Wolbachia. Mol. Ecol. 19, 1940–1952. 17. Russell, J.A., Goldman-Huertas, B., Moreau, C.S., Baldo, L., Stahlhut, J.K., Werren, J.H., and Pierce, N.E. (2009). Specialization and geographic isolation among Wolbachia symbionts from ants and Lycaenid butterflies. Evolution 63, 624–640. 18. Caspi-Fluger, A., Inbar, M., Mozes-Daube, N., Katzir, N., Portnoy, V., Belausov, E., Hunter, M.S., and Zchori-Fein, E. (2012). Horizontal transmission of the insect symbiont Rickettsia is plant-mediated. Proc. Biol. Sci. 279, 1791–1796. 19. Moran, N.A., and Dunbar, H.E. (2006). Sexual acquisition of beneficial symbionts in aphids. Proc. Natl. Acad. Sci. USA 103, 12803–12806. 20. Gehrer, L., and Vorburger, C. (2012). Parasitoids as vectors of facultative bacterial endosymbionts in aphids. Biol. Lett. 8, 613–615.
Department of Entomology, University of Kentucky, Lexington, KY 40546, USA. E-mail: [email protected]
http://dx.doi.org/10.1016/j.cub.2013.07.069
requiring only familiarity-based judgments should be spared after selective hippocampal damage and impaired after damage to the perirhinal cortex. Indeed, a substantial literature involving lesions, single-unit recordings and neuroimaging is consistent with this view [3]. A compelling component of this literature is the numerous studies reporting spared familiarity-based recognition memory in animals with selective hippocampal damage or disruption [4]. In this issue of Current Biology, Cohen et al. [5] challenge this perspective by reporting in a series of eleven experiments that reversible disruption of the mouse hippocampus during memory encoding, retention or retrieval profoundly impairs performance on the novel object recognition task — a task that can be accomplished using only familiarity-based recognition memory. These findings were obtained even when potential spatial confounds were eliminated. Further, the authors found that extracellular glutamate efflux in the
Current Biology Vol 23 No 17 R726
CA 3 Mossy fibers
Schaffer collaterals
CA 1
Temporoammonic pathways
S
DG Perforant pathway II
III
IV
V
Entorhinal cortex Medial
Parahippocampal / postrhinal cortex
Lateral
Perirhinal cortex
Unimodal and polymodal association areas (frontal, temporal, and parietal lobes) Neocortex Current Biology
Figure 1. Schematic view of the primary connections of the hippocampus. The hippocampus (highlighted in red), defined here as the dentate gyrus (DG), CA3, CA1, and subiculum (S), is anatomically situated to receive highly processed information from widespread neocortical regions through three temporal cortical areas, the entorhinal, perirhinal, and parahippocampal cortices (in the rat, the term postrhinal cortex replaces the term parahippocampal cortex), as well as through other direct projections to the entorhinal cortex from areas outside the temporal lobe. The figure shows a simplified view of the way in which information enters the hippocampus from the superficial layers (II and III) of the entorhinal cortex and then flows in a largely unidirectional feed-forward direction to the deep layers of entorhinal cortex (IV and V). The medial entorhinal cortex is densely connected with the postrhinal cortex and is specialized for spatial information, while the lateral entorhinal cortex is densely connected with the perirhinal cortex and is specialized for object information. These two processing streams are primarily combined when they reach the hippocampus.
hippocampus and the firing properties of hippocampal neurons during performance of the recognition memory task are consistent with the involvement of the hippocampus in familiarity-based recognition memory. Early Insights into the Anatomy of Memory On September 1, 1953 at Hartford Hospital in Hartford Connecticut, the
neurosurgeon William Scoville excised bilaterally the medial temporal lobes of a patient with severe epilepsy. The surgery was an attempt to reduce the severity of the patient’s seizures, and in this regard the surgery was a success. The bilateral removal of the medial temporal lobes, however, also left the patient with profound amnesia. The subsequent systematic evaluation of this patient, known now as H.M.,
ushered in the modern era of memory research. Work with H.M. and with other patients with similar damage has established four fundamental principles of memory [6]. First, memory is a distinct cerebral ability, in large part separate from other cognitive functions such as perception, intelligence, personality and motivation. Second, only long-term memory is disrupted because information could be maintained and utilized for a short time in working memory. Third, medial temporal lobe structures are not the ultimate repository of long-term memory, because remote memory remained largely intact. Fourth, despite the debilitating and pervasive memory impairment, motor skills memory could still be acquired — providing the first clues that memory is not a single phenomenon [7]. At the time that H.M. was first described [8], there was some evidence to suggest the hippocampus might be the critical structure for the memory impairment. However, although the term ‘hippocampus’ was used in the title of the classic 1957 paper [8], the authors explicitly noted that the specific contributions of the hippocampus to the memory impairment must remain tentative because other structures were also damaged by the surgery, including the amygdala and cortical regions adjacent to the hippocampus and amygdala. Accordingly, efforts began almost immediately to develop an animal model of medial temporal lobe amnesia. An Animal Model of Recognition Memory Despite rapid and vigorous efforts to develop an animal model of H.M.’s amnesia, an animal model would not be achieved for more than 20 years. The primary difficulty was that, during the 1960s and 1970s, it was not yet appreciated that different learning and memory tasks could be supported by different brain systems [9]. Many of the tasks given to animals with hippocampal lesions were ones that they could learn as a skill or habit, even if humans tended to learn the task by memorizing the material. Establishing an animal model of human memory impairment would require developing tasks for animals that assessed the same kind of memory that is impaired in humans after medial temporal lobe damage [10].
Dispatch R727
The key development was the creation of a ‘one-trial’ test of recognition memory, where monkeys were first trained to select an object that was previously encountered (delayed matching-to-sample, DMS) or, in another version, select a novel object that was paired with a previously encountered object (delayed nonmatching-to-sample, DNMS). Because new objects were used on each trial, animals were prevented from solving the task gradually using habit memory. In 1978, it was reported that monkeys with lesions designed to mimic H.M.’s damage exhibited a similar memory impairment profile to H.M. when tested on the DNMS task [11]. This study signaled the successful development of an animal model of recognition memory in the monkey and led eventually to the identification of the structures comprising the medial temporal lobe memory system [12]. The model was also extended to include rodents, and in the rodents the DMS and DNMS tasks were eventually supplanted by one-trial spontaneous recognition memory tasks [13,14], similar to the one used by Cohen et al. [5] in their new work. The Anatomy of Recognition Memory The system of brain structures important for memory includes the hippocampus and the adjacent entorhinal, perirhinal and parahippocampal cortices (Figure 1). While the hippocampus was the early focus for most of the work with the animal model, it was eventually discovered that selective damage to the cortical regions adjacent to the hippocampus, particularly the perirhinal cortex, produced more profound recognition memory impairments than selective damage to the hippocampus itself (for review see [13]). As noted above, it has become common in modern
formulations to deemphasize the role of the hippocampus in familiarity-based recognition memory performance [3,4,15–17]. Thus, the new work of Cohen et al. [5] is timely and makes the important observation that the hippocampus itself appears to be critically involved in familiarity-based recognition memory. Summary One way to view the function of the hippocampus is that it sits at the end of a processing hierarchy of the medial temporal lobe, receiving input from both the perirhinal and parahippocampal cortices, largely by way of the entorhinal cortex. Guided by the anatomy, it seems reasonable that the hippocampus extends and combines functions performed by the structures that project to it. By this view, the hippocampus and other structures of the medial temporal lobe, like the perirhinal cortex, work together in a cooperative and complementary manner [18]. Finally, the work by Cohen et al. [5] and others [13,18] suggest that the anatomy of familiarity-based and recollection-based recognition memory may not be a straightforward anatomical dichotomy. To understand the substrates of recognition memory more precisely it will be important to continue to develop methods to determine how tasks are approached and to identify the critical information that is used to support performance. References 1. Brown, M.W., and Aggleton, J.P. (2001). Recognition memory: what are the roles of the perirhinal cortex and hippocampus? Nat. Rev. Neurosci. 2, 51–61. 2. Squire, L.R., Wixted, J.T., and Clark, R.E. (2007). Recognition memory and the medial temporal lobe: A new perspective. Nat. Rev. Neurosci. 8, 872–883. 3. Eichenbaum, H., Yonelinas, A.R., and Ranganath, C. (2007). The medial temporal lobe and recognition memory. Annu. Rev. Neurosci. 30, 123–152. 4. Winters, B.D., Saksida, L.M., and Bussey, T.J. (2008). Object recognition memory: neurobiological mechanisms of encoding,
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Veterans Affairs Medical Center, San Diego, CA 92161 and University of California, San Diego, School of Medicine, 9500 Gilman, La Jolla, CA 92093, USA. E-mail: [email protected]
http://dx.doi.org/10.1016/j.cub.2013.07.037