Dissecting spatial knowledge from spatial choice by hippocampal NMDA receptor deletion

Bannerman, David M.; Bus, Thorsten; Taylor, Amy; Sanderson, David J.; Schwarz, Inna; Jensen, Vidar R.; Hvalby, Øivind; Rawlins, J. N. P.; Seeburg, Peter H.; Sprengel, Rolf

doi:10.1038/nn.3166

Cited by 142 publications

(193 citation statements)

References 53 publications

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“…The Tg29-1 Grin1 knockout mice were, after all, impaired during acquisition of the standard SRM version of the watermaze task, although they were also mildly impaired on the visible platform task 45 . Taken in combination with the absence of a watermaze impairment in our hippocampus-specific Grin1 ΔDGCA1 mice 33 , these data demonstrate that extra-hippocampal NMDARs make an important contribution to associative, long-term spatial memory. A similar conclusion can be reached by comparing across studies with conditional NMDAR GluN2B subunit knockout mice.…”

Section: Extra-hippocampal Nmdars and Long-term Spatial Memorysupporting

confidence: 59%

“…However, the SRM radial maze impairment in the Grin1 ΔDGCA1 mice is independent of the spatial separation between the arms of the maze (Figure 2c, right) 33,51 . Furthermore, the various watermaze results demonstrate that Grin1 ΔDGCA1 mice can successfully discriminate between, and use the extramaze spatial cues perfectly well.…”

Section: Reappraising the Role Of The Hippocampus In Pattern Separationmentioning

confidence: 95%

“…ΔDGCA1 mice are also impaired during spatial reversal in the watermaze (Figure 2b, right) 33 . The watermaze reversal paradigm generates conflict and ambiguity between the old and new platform locations.…”

Section: Grin1mentioning

confidence: 96%

“…associating particular spatial locations within a cognitive map with particular events or outcomes or stimuli) has been widely accepted 26 , and has only rarely been questioned [27][28][29][30][31][32] . However, recent evidence from a novel genetically modified mouse line challenges the relationship between hippocampal LTP and long-term, associative spatial memory formation 33 .…”

Section: Synaptic Plasticity and Spatial Memory Formationmentioning

confidence: 99%

“…Thus NMDARs in the hippocampal CA1 subfield are not required for encoding and/or storing associative long-term spatial memories 33 . Note also, ablation of NMDARs from either DG alone or from CA3 does not impair SRM acquisition in the watermaze 63,70 .…”

Section: Extra-hippocampal Nmdars and Long-term Spatial Memorymentioning

confidence: 99%

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Hippocampal synaptic plasticity, spatial memory and anxiety

et al. 2014

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. (2014) 'Hippocampal synaptic plasticity, spatial memory and anxiety.', Nature reviews neuroscience., 15 (3). pp. 181-192. Further information on publisher's website:https://doi.org/10.1038/nrn3677Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractRecent studies with transgenic mice lacking NMDARs in the hippocampus challenge head-on the longstanding hypothesis that hippocampal LTP-like mechanisms underlie the encoding and storage of associative, long-term spatial memories. However, it may not be the synaptic plasticity/memory hypothesis that is wrong. Instead, it may be the role of the hippocampus that needs re-examination. We present an account of hippocampal function which explains its role in both memory and anxiety.3

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Section: Extra-hippocampal Nmdars and Long-term Spatial Memorysupporting

confidence: 59%

Section: Reappraising the Role Of The Hippocampus In Pattern Separationmentioning

confidence: 95%

Section: Grin1mentioning

confidence: 96%

Section: Synaptic Plasticity and Spatial Memory Formationmentioning

confidence: 99%

Section: Extra-hippocampal Nmdars and Long-term Spatial Memorymentioning

confidence: 99%

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Hippocampal synaptic plasticity, spatial memory and anxiety

et al. 2014

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Increased anxiety‐like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model

Quarta

Bravi

Scambi

et al. 2015

J of Comparative Neurology

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Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease primarily characterized by motor neuron death, causes damages beyond motor-related areas. In particular, cognitive impairments and hippocampal damage have been reported in ALS patients. We investigated spatial navigation learning and hippocampal interneurons in a mutant SOD1(G93A) mouse (mSOD1) model of ALS. Behavioral tests were performed by using presymptomatic mSOD1 mice. General motor activity was comparable to that of wild-type mice in the open-field test, in which, however mSOD1 exhibited increased anxiety-like behavior. In the Barnes maze test, mSOD1 mice displayed a delay in learning, outperformed wild-type mice during the first probe trial, and exhibited impaired long-term memory. Stereological counts of parvalbumin-positive interneurons, which are crucial for hippocampal physiology and known to be altered in other central nervous system regions of mSOD1 mice, were also performed. At postnatal day (P) 56, the population of parvalbumin-positive interneurons in mSOD1 mice was already reduced in CA1 and in CA3, and at P90 the reduction extended to the dentate gyrus. Loss of parvalbumin-positive hippocampal interneurons occurred mostly during the presymptomatic stage. Western blot analysis showed that hippocampal parvalbumin expression levels were already reduced in mSOD1 mice at P56. The hippocampal alterations in mSOD1 mice could at least partly account for the increased anxiety-like behavior and deficits in spatial navigation learning. Our study provides evidence for cognitive alterations and damage to the γ-aminobutyric acid (GABA)ergic system in the hippocampus of murine ALS, thereby revealing selective deficits antecedent to the onset of motor symptoms.

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Increase in hippocampal theta oscillations during spatial decision making

et al. 2014

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The processing of spatial and mnemonic information is believed to depend on hippocampal theta oscillations (5–12 Hz). However, in rats both the power and the frequency of the theta rhythm are modulated by locomotor activity, which is a major confounding factor when estimating its cognitive correlates. Previous studies have suggested that hippocampal theta oscillations support decision-making processes. In this study, we investigated to what extent spatial decision making modulates hippocampal theta oscillations when controlling for variations in locomotion speed. We recorded local field potentials from the CA1 region of rats while animals had to choose one arm to enter for reward (goal) in a four-arm radial maze. We observed prominent theta oscillations during the decision-making period of the task, which occurred in the center of the maze before animals deliberately ran through an arm toward goal location. In speed-controlled analyses, theta power and frequency were higher during the decision period when compared to either an intertrial delay period (also at the maze center), or to the period of running toward goal location. In addition, theta activity was higher during decision periods preceding correct choices than during decision periods preceding incorrect choices. Altogether, our data support a cognitive function for the hippocampal theta rhythm in spatial decision making.

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Dissecting spatial knowledge from spatial choice by hippocampal NMDA receptor deletion

Cited by 142 publications

References 53 publications

Hippocampal synaptic plasticity, spatial memory and anxiety

Hippocampal synaptic plasticity, spatial memory and anxiety

Increased anxiety‐like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model

Increase in hippocampal theta oscillations during spatial decision making

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