Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation

doi:10.1007/s11515-016-1406-2

Frontiers in Biology

2016, Vol. 11

Issue (3): 168-181 https://doi.org/10.1007/s11515-016-1406-2

本期目录

Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation

Martha Hvoslef-Eide^1,^2,³,Charlotte A. Oomen^4,^5,^6,^*(

)

¹. Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
². Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3 EB, United Kingdom
³. Current addess Department of Biosciences, University of Oslo, 0370 Oslo, Norway
⁴. Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute, Geert Grooteplein 21, 6500 HB, Nijmegen, The Netherlands
⁵. Current address Centre for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands
⁶. Current address Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

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Abstract：

The ability to discriminate and store similar inputs as distinct representations in memory is thought to rely on a process called pattern separation in the dentate gyrus of the hippocampus. Recent computational and empirical findings support a role for adult-born granule neurons in spatial pattern separation. We reviewed rodent studies that have manipulated both hippocampal adult neurogenesis and assessed pattern separation. The majority of studies report a supporting role of adult born neurons in pattern separation as measured at the behavioral level. However, closer evaluation of the published findings reveals variation in both pattern separation tasks and in the interpretation of behavioral performance that, taken together, suggests that the role of hippocampal adult neurogenesis in pattern separation may be less established than is currently assumed. Assessment of pattern separation at the network level through the use of immediate early gene expression, optogenetic, pharmacogenetic and/or in vivo electrophysiology studies could be instrumental in further confirming a role of adult born neurons in pattern separation further. Finally, hippocampal adult neurogenesis and pattern separation are not an exclusive pair, as evidence for hippocampal adult neurogenesis contributing to the temporal separation of events in memory, forgetting and cognitive flexibility has also been found. We conclude that whereas current empirical evidence for the involvement of hippocampal adult neurogenesis in pattern separation seems supportive, there is a need for careful interpretation of behavioral findings and an integration of the various proposed functions of adult born neurons.

Key words： adult neurogenesis memory pattern separation dentate gyrus behavioral paradigms

收稿日期: 2016-03-22 出版日期: 2016-07-05

Corresponding Author(s): Charlotte A. Oomen

引用本文:

. [J]. Frontiers in Biology, 2016, 11(3): 168-181.
Martha Hvoslef-Eide,Charlotte A. Oomen. Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation. Front. Biol., 2016, 11(3): 168-181.

链接本文:

https://academic.hep.com.cn/fib/CN/10.1007/s11515-016-1406-2
https://academic.hep.com.cn/fib/CN/Y2016/V11/I3/168

	Effect on task(s)	Dissimilar condition?	Support role of NG in PS?	Change in NG/experimental manipulation	Species/Sex/Age	Reference
1	Impaired novel object in place recognition memory	No	Yes	Decreased NG after early malnutrition	Rat/m/-	Perez-Garcia et al., 2016
2	No effect on location discrimination learning (touchscreen)	Yes	No	Increased NG after electroconvulsive seazures	Rat/m/8+ weeks	Svensson et al., 2016
3	Improved performance on the DNMTP radial arm maze	Yes	Yes	Innate higher levels of NG correlate positively with task performance in male spatial strategy users.	Rat/m and f/10+ weeks	Yagi et al., 2016
4	Improved performance on contextual fear discrimination (in 3 month old mice)	No	Yes	Increased NG after fingolimod treatment	Mice/m/ 3,7,12 months	Efstathopoulos et al., 2015
5	No effect on contextual fear discrimination	No	No	Decreased NG in a Dorfin homozygous knockout mouse	Mice/-/-	Park et al., 2015
6	No effect on trial-unique nonmatching to location (touchscreen)	Yes	No	Increased neurogenesis after electroconvulsive seazures	Rat/m/8+weeks	Svensson et al., 2015
7	Improved contextual fear discrimination	No	Yes	Increased NG after postnatal sevoflurane treatment	Rat/m/5–8 weeks	Chen et al., 2015
8	Impaired learning in a high-interference condition of submerged T-maze paradigm	Yes, low interference	Yes	Decreased NG after chemotherapy drug treatment	Rat/f/5 months	Winocur et al., 2015
9	Improved contextual fear discrimination after running in aged animals	No	Yes	Decreased NG in aging, increased neurogenesis after voluntary exercise	Mice/m/2,17 months	Wu et al., 2015
10	Improved novel object recognition of similar, but not distinct objects	Yes	Yes	Increased NG after voluntary exercise	Mice/f/8+ weeks	Bolz et al., 2015
11	Impaired contextual fear discrimination	No	Yes	Decreased survival and changed dendritic complexity after PS1 knockdown of adult-born neurons	Mice/m/8 months	Bonds et al., 2015
12	Improved spontaneous location recognition memory	Yes	Yes	Increased NG after systemic ghrelin administration	Rats/m/8+ weeks	Kent et al., 2015
13	Impaired performance on a spatial metric task and temporal object association task	No	Yes	Decreased NG in DNMT-1 knockout mice	Mice/m/1–3 months	Kesner et al., 2014
14	Impaired performance on similar and dissimilar trials in the location discrimination task during reversal only.	Yes	No	Decreased NG in GFAP-TK mice	Mice/m/8+ weeks	Swan et al., 2014
15	Impaired object-in-place memory	No	Yes	Decreased NG due to inflammatory factors (and normalization through ibuprofen treatment)	Mice/f/8+ weeks	Llorens-Martin et al., 2014
16	Impaired spontaneous location recognition memory	Yes	Yes	Decreased NG through viral delivery of Wnt	Rats/m/8+ weeks	Bekinschtein et al.,2014
17	Impaired contextual fear discrimination (use of randomized and non-randomized version)	No	Yes	Decreased NG (dorsal versus ventral) through X-ray irradiation	Mice/m/7+ weeks	Wu and Hen, 2014
18	Impaired contextual fear discrimination and subsequent normalization	No	Yes	Decreased NG (Btg1 mice) and normalization using voluntary exercise	Mice/-/8+ weeks	Farioli-Vecchioli et al., 2014
19	Impaired DNMTP in the radial arm maze at both small and large separations	Yes	Yes	Decreased NG in Ezh2knockout mice	Mice/m/-	Zhang et al., 2014
20	More perseverance in the Morris water maze, less precise search patterns.	No	Yes	Decreased NG in Cyclin-D2 knockout mice	Mice/f/8+ weeks	Garthe et al., 2014
21	Impaired contextual fear discrimination (reported in separate study: Jin et al., 2013)	No	Yes	Decreased NG in Ras/Grf1 knockout mice	Mice/-/-	Darcy et al., 2014 (Jin et al., 2013)
22	No effect on contextual fear discrimination	No	No	Increased NG in Pet knockout mice (serotonin depletion)	Mice/m/8–10 weeks	Diaz et al., 2013
23	No effect on DNMTP in the radial arm maze at small or large separations	Yes	No	Decreased NG in GFAP-TK rats	Rats/m/8 weeks	Groves et al., 2013
24	Impaired performance on small separation in touchscreen location discrimination	Yes	Yes	Decreased NG in TNiK knockout mice	Mice/m/8+ weeks	Coba et al., 2012
25	Impaired and improved novel object in place memory	Yes	Yes	Decreased NG in SREB2 transgenic mice/ Increased NG in SREB2 knockout mice	Mice/m/4–6 months	Chen et al., 2012
26	Impaired cognitive flexibility	No	Yes	Decreased NG in GFAP-TK mice and after X-ray irradiation	Mice/m/10+ weeks	Burghardt et al., 2012
27	Impaired contextual fear discrimination	Yes, in a separate experiment	Yes	Deletion of NR2B of the NMDAR in adult born neurons only;	Mice/m/14–16 weeks	Kheirbek et al., 2012
28	Impaired contextual fear discrimination after NG ablation (main finding: improved performance upon inhibited neurotransmission of adult cells)	Yes, in a separate experiment	Yes	Inhibited neurotransmission of adult granule cells in combination with decreased NG after X-ray irradiation.	Mice/m/14+ weeks	Nakashiba et al., 2012
29	Impaired performance on a high interference odor discrimination paradigm	No	Yes	Decreased NG after X-ray irradiation	Rats/m/3+ months	Luu et al., 2012
30	Impaired DNMTP in the radial arm maze at both small and large separations	Yes	Yes	Decreased NG in ERK5 inducable knockout (adult born neurons only)	Mice/m/12 weeks	Pan et al., 2012
31	Improved contextual fear discrimination in males, no effect in females	No	No	Ablation of postnatal NG in DNMT1 knockout mice	Mice/m and f/ 3–5 months	Cushman et al., 2012
32	Impaired contextual fear conditioning	Yes	Yes	Ablation of NG using HSV-tk under the nestin promotor and by means of systemic temozolomide treatment	Mice/m/10 weeks	Niibori et al., 2012
33	Impaired performance on an adapted version of the Barnes’ maze	No	Yes	NF-kB knockout results in a (pathological) increase in NG	Mice/m/-	Imielski et al., 2012
34	Improved performance in a submerged radial arm maze (and a lack thereof in knockout animals)	Yes	Yes	Increased NG in control animals after enrichment; and a lack thereof in mice with conditional knock-out of CREB binding protein	Mice/f/2–5 months(?)	Lopez-Atalaya et al., 2011
35	Improved (and impaired) contextual fear discrimination (normal absence of fear memory in novel context)	No	Yes	Increase (and decrease) in NG through genetic manipulation and X-ray irradiation.	Mice/m and f/14–18 weeks	Sahay et al., 2011
36	Impaired contextual fear discrimination	No	Yes	Decreased NG in Nestin rtTA/Tet mice	Mice/m/8 weeks	Tronel et al., 2010
37	Improved location discrimination learning (touchscreen)	Yes	Yes	Increased NG after running	Mice/m/3 and 22 months	Creer et al., 2010
38	Improved location discrimination learning and improved DNMTP in the radial arm maze (on similar conditions only)	Yes	Yes	Decreased NG after X-ray irradiation and viral delivery of Wnt knockdown	Mice/f/8+ weeks	Clelland et al., 2009

Tab.1

Fig.1

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