The Effects of GluA1 Deletion on the Hippocampal Population Code for Position

Resnik, Evgeny; McFarland, James M.; Sprengel, Rolf; Sakmann, Bert; Mehta, Mayank R.

doi:10.1523/jneurosci.6460-11.2012

Cited by 44 publications

(55 citation statements)

References 87 publications

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“…Alternatively, the motifs could arise in the medial entorhinal cortex, where neurons show motif-like activity lasting several seconds and robustly driving the CA1, even in anesthetized or sleeping animals 43 . Accordingly, sustained spiking in consecutive theta cycles was reduced, indicative of diminished motifs, in a GluA1 transgenic mouse with diminished distal dendritic inputs, which typically originate in the entorhinal cortex 44 . Motif-field durations could also be modulated by the temporal integration properties of the h current 45 to generate a dorsoventral gradient of field sizes.…”

Section: Discussionmentioning

confidence: 97%

“…The impaired spatial selectivity in rats in two-dimensional VR is similar to the weak spatial selectivity seen in human studies, in which such pairings are absent as well. Recent studies have shown that a sufficiently large pool of hippocampal neurons can provide accurate spatial information despite impaired spatial selectivity in one-dimensional environments 44 ; such a distributed coding mechanism might also allow rodents and humans to solve spatial tasks in two-dimensional VR. Our results suggest that in human and primate studies in VR, repeated pairing of a rich variety of stimuli, especially between motor and visual cues, could enhance neural activity and spatial selectivity.…”

Section: Discussionmentioning

confidence: 99%

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Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality

et al. 2014

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During real-world (RW) exploration, rodent hippocampal activity shows robust spatial selectivity, which is hypothesized to be governed largely by distal visual cues, although other sensory-motor cues also contribute. Indeed, hippocampal spatial selectivity is weak in primate and human studies that use only visual cues. To determine the contribution of distal visual cues only, we measured hippocampal activity from body-fixed rodents exploring a two-dimensional virtual reality (VR). Compared to that in RW, spatial selectivity was markedly reduced during random foraging and goal-directed tasks in VR. Instead we found small but significant selectivity to distance traveled. Despite impaired spatial selectivity in VR, most spikes occurred within ~2-s-long hippocampal motifs in both RW and VR that had similar structure, including phase precession within motif fields. Selectivity to space and distance traveled were greatly enhanced in VR tasks with stereotypical trajectories. Thus, distal visual cues alone are insufficient to generate a robust hippocampal rate code for space but are sufficient for a temporal code. npg © 2015 Nature America, Inc. All rights reserved.1 2 2 VOLUME 18 | NUMBER 1 | JANUARY 2015 nature neurOSCIenCe a r t I C l e S same physical location in space can be approached from multiple different directions at different speeds. We thus investigated the contribution of distal visual cues only in determining selectivity in such an experimental setup. RESULTS Nature of spatial selectivity of hippocampal responsesWe measured hippocampal activity during a two-dimensional randomforaging task in RW and VR [35][36][37] with similar distal visual cues (Fig. 1a). In VR, the rats were body-fixed, i.e., their bodies were held in place, with a harness on a floating ball, allowing for head movements but precluding full-body turns, thus minimizing vestibular cues (Online Methods) 21,36 . Rats quickly learned to avoid the virtual edges entirely on the basis of visual cues 36 and spent a similar amount of time away from the edges and in the center of the platform (Fig. 1a) compared to in RW. We measured the activity of 1,066 and 1,238 principal neurons in RW and VR, respectively, in the dorsal CA1 of four rats under a variety of conditions (Online Methods). Neurons fired vigorously in restricted regions of space in RW, as expected (Fig. 1b,c, Supplementary Fig. 1a and Supplementary Video 1) 1 . In contrast, the neurons showed little spatial selectivity in VR during random foraging (Fig. 1b,d and Supplementary Fig. 1b).Across the ensemble, neurons had moderately reduced (25%) mean firing rates but greatly reduced (68%) peak firing rates in VR ( Fig. 2a and Supplementary Fig. 2a). Neurons in VR also had greatly reduced spatial information content (75%), stability (59%), sparsity (42%) and coherence (40%) (Fig. 2b-d and Supplementary Fig. 2b,c) compared to spatially localized, stable and sparse RW rate maps (Fig. 2c). Although the mean firing rate was inversely correlated with information content (Supplementary Fig. 2d)...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality

et al. 2014

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“…20,129,130 . In line with a hypothesis that the hippocampus acquires and encodes spatial information, it was argued that the residual spatial coding in GluA1-lacking neurons may still be sufficient to perform SRM tasks, and that taken across the entire neuronal population the decoding accuracy is still far better than chance levels 128 . It was also argued that SRM tasks might just be less sensitive than SWM tasks, and that working memory performance may be particularly sensitive to place cell disruption because it requires a flexible representation of position that is rapidly modified by trialspecific information.…”

Section: What Is Anxiety?mentioning

confidence: 93%

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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“…It is clear that, since their inception 1,12 , brain recordings from awake behaving animals have greatly advanced our understanding of how neurons and networks of neurons encode behaviorally relevant events 3,4,13,14 . In particular, brain recordings from genetically modified mice have allowed the identification of molecular cascades that are crucially involved in neural encoding [15][16][17] . Importantly, the technique has only recently been applied to clinically oriented issues 17,18 .…”

Section: Discussionmentioning

confidence: 99%

Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

Chang

Frattini

Robbiati

et al. 2013

JoVE

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State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field potentials (LFPs) from populations of neurons and action potentials from individual cells, as the animal engages in experimentally relevant tasks. Chronically implanted microdrives allow for brain recordings to last over periods of several weeks. Miniaturized drives and lightweight components allow for these long-term recordings to occur in small mammals, such as mice. By using tetrodes, which consist of tightly braided bundles of four electrodes in which each wire has a diameter of 12.5 μm, it is possible to isolate physiologically active neurons in superficial brain regions such as the cerebral cortex, dorsal hippocampus, and subiculum, as well as deeper regions such as the striatum and the amygdala. Moreover, this technique insures stable, high-fidelity neural recordings as the animal is challenged with a variety of behavioral tasks. This manuscript describes several techniques that have been optimized to record from the mouse brain. First, we show how to fabricate tetrodes, load them into driveable tubes, and gold-plate their tips in order to reduce their impedance from MΩ to KΩ range. Second, we show how to construct a custom microdrive assembly for carrying and moving the tetrodes vertically, with the use of inexpensive materials. Third, we show the steps for assembling a commercially available microdrive (Neuralynx VersaDrive) that is designed to carry independently movable tetrodes. Finally, we present representative results of local field potentials and single-unit signals obtained in the dorsal subiculum of mice. These techniques can be easily modified to accommodate different types of electrode arrays and recording schemes in the mouse brain. Video LinkThe video component of this article can be found at

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The Effects of GluA1 Deletion on the Hippocampal Population Code for Position

Cited by 44 publications

References 87 publications

Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality

Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality

Hippocampal synaptic plasticity, spatial memory and anxiety

Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

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