Intact spatial memory in mice with seizure-induced partial lossof hippocampal pyramidal neurons

Mohajeri, M. Hasan; Saini, Krishan; Li, Hong; Crameri, Arames; Lipp, Hans‐Peter; Wolfer, David P; Nitsch, Roger M.

doi:10.1016/s0969-9961(02)00031-1

Cited by 27 publications

(36 citation statements)

References 44 publications

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“…The idea became a focus in AHN research because computational modeling showed that changing the excitability of relatively few dispersed granule cells could establish new input channels into the hippocampal subfields [Yassa and Stark, 2011]. The model provided an explanation for the vexing problem of how few newly generated cells in the dentate gyrus could have functional relevance, while partial removal of the hippocampus or a 25% reduction of the number of pyramidal cells by lesions did not affect water maze learning [Mohajeri et al, 2003]. …”

Section: Are Actual Behavioral Tests Ecologically Relevant For Rodents?mentioning

confidence: 99%

Adult Neurogenesis in Mammals: Variations and Confusions

Lipp

Bonfanti

2016

Brain Behav Evol

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Mammalian adult neurogenesis has remained enigmatic. Two lines of research have emerged. One focuses on a potential repair mechanism in the human brain. The other aims at elucidating its functional role in the hippocampal formation, chiefly in cognitive processes; however, thus far it has been unsuccessful. Here, we try to recognize the sources of errors and conceptual confusion in comparative studies and neurobehavioral approaches with a focus on mice. Evolutionarily, mammalian adult neurogenesis appears as protracted juvenile neurogenesis originating from precursor cells in the secondary proliferation zones, from where newly formed cells migrate to target regions in the forebrain. This late developmental process is downregulated differentially in various brain structures depending on species and age. Adult neurogenesis declines substantially during early adulthood and persists at low levels into senescence. Short-lasting episodes in proliferation or reduction of adult neurogenesis may reflect a multitude of factors, and have been studied chiefly in mice and rats. Comparative studies face both species-specific variations in staining and technical abilities of laboratories, lacking quantification of important reference measures (e.g. granule cell number) and evaluation of maturational markers whose persistence might be functionally more relevant than proliferation rates. Likewise, the confusion about the functional role of variations in adult hippocampal neurogenesis has many causes. Prominent is an inferential statistical approach, usually with low statistical power. Interpretation is complicated by multiple theories about hippocampal function, often unrealistically extrapolating from humans to rodents. We believe that the field of mammalian adult neurogenesis needs more critical thinking, more sophisticated hypotheses, better statistical, technical and behavioral approaches, and a broader conceptual perspective incorporating comparative aspects rather than neglecting them.

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Section: Are Actual Behavioral Tests Ecologically Relevant For Rodents?mentioning

confidence: 99%

Adult Neurogenesis in Mammals: Variations and Confusions

Lipp

Bonfanti

2016

Brain Behav Evol

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“…A modified MWM protocol was employed as described previously [2]. Briefly, training and testing of mice were performed under 12 lux diffuse light in a circular pool constructed from white polypropylene (diameter 150 cm, wall height 50 cm), filled with opaque water to a height of 16 cm and maintained at 24-26°C.…”

Section: Morris Water Mazementioning

confidence: 99%

“…Ab accumulation is proposed to result from an imbalance between Ab production and clearance and to induce the formation of neurofibrillary tangles [1]. The hippocampal formation is one of the first areas affected by AD and hippocampal CA1 and CA3 neurons are instrumental for learning and memory in rodents, nonhuman primates, and humans [2][3][4][5]. The finding that familial AD is caused by mutations in genes encoding the amyloid precursor protein (APP) and presenilins, leading to high production of the Ab peptides in the brain, has established the importance of over-production of Ab in AD pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Neprilysin Deficiency-Dependent Impairment of Cognitive Functions in a Mouse Model of Amyloidosis

Mohajeri

Wolfer

2009

Neurochem Res

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Alzheimer's disease, responsible for the vast majority of dementia cases in the elderly population, is caused by accumulation of toxic levels of amyloid beta peptide (A beta) in the brain. Neprilysin is a major enzyme responsible for the degradation of A beta in vivo. We have previously shown that elevation of neprilysin levels in the brain delays the deposition of A beta-plaques in a mouse model of amyloidosis and that lack of neprilysin leads to increased A beta generation and to signs of incipient neurodegeneration in mouse brains. This study was designed to test whether low brain levels of neprilysin affect the amyloid pathology or perturb the learning and memory performance of mice. Double-mutated mice carrying a targeted depletion of one allele of Mme, the gene encoding neprilysin, and over-expressing human amyloid precursor protein (APP), exhibited a reinforced amyloid pathology in comparison with their APP transgenic littermates. Moreover, in contrast to their parental lines, these mice were impaired in the Morris water maze learning and memory paradigm and showed facilitated extinction in the conditioned taste aversion test. These data suggest that even a partial neprilysin deficiency, as is found during aging, exacerbates amyloid pathology and may impair cognitive functions.

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“…Although a visible platform version of the water maze is typically conducted to partial out spatial, hippocampally-mediated learning from nonspatial, hippocampal-independent processes, this dissociation has been shown to be less than perfect in mice. Specifically, inbred wild-type mice with excitotoxic or seizure-induced lesions of the hippocampus or entorhinal cortex are often impaired on both in the hidden-and visible-platform versions of the water maze (Hardman et al 1997;Logue et al 1997;Lipp and Wolfer 1998;Mohajeri et al 2003Mohajeri et al , 2004Lipp et al 2004). It is not clear from these studies whether hippocampal insults impair the ability to make the association between the escape platform and the discrete cue, or whether mice attempt to use a spatial strategy to solve the cued-platform version and are unable because of the lesion Hauben et al 1999;Janus 2004).…”

mentioning

confidence: 99%

Spatial and nonspatial escape strategies in the Barnes maze

Harrison¹,

Reiserer²,

Tomarken³

et al. 2006

Learn. Mem.

198

167

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The Barnes maze is a spatial memory task that requires subjects to learn the position of a hole that can be used to escape the brightly lit, open surface of the maze. Two experiments assessed the relative importance of spatial (extra-maze) versus proximal visible cues in solving the maze. In Experiment 1, four groups of mice were trained either with or without a discrete visible cue marking the location of the escape hole, which was either in a fixed or variable location across trials. In Experiment 2, all mice were trained with the discrete visible cue marking the target hole location. Two groups were identical to the cued-target groups from Experiment 1, with either fixed or variable escape locations. For these mice, the discrete cue either was the sole predictor of the target location or was perfectly confounded with the spatial extra-maze cues. The third group also used a cued variable target, but a curtain was drawn around the maze to prevent the use of spatial cues to guide navigation. Probe trials with all escape holes blocked were conducted to dissociate the use of spatial and discrete proximal cues. We conclude that the Barnes maze can be solved efficiently using spatial, visual cue, or serial-search strategies. However, mice showed a strong preference for using the distal room cues, even when a discrete visible cue clearly marked the escape location. Importantly, these data show that the cued-target control version of the Barnes maze as typically conducted does not dissociate spatial from nonspatial abilities.

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Intact spatial memory in mice with seizure-induced partial lossof hippocampal pyramidal neurons

Cited by 27 publications

References 44 publications

Adult Neurogenesis in Mammals: Variations and Confusions

Adult Neurogenesis in Mammals: Variations and Confusions

Neprilysin Deficiency-Dependent Impairment of Cognitive Functions in a Mouse Model of Amyloidosis

Spatial and nonspatial escape strategies in the Barnes maze

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