Path integration in normal aging and Alzheimer’s disease

Segen, Vladislava; Ying, Johnson; Morgan, Erik; Brandon, Mark P.; Wolbers, Thomas

doi:10.1016/j.tics.2021.11.001

Cited by 32 publications

(24 citation statements)

References 131 publications

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“…Path integration not only makes it possible for an animal to navigate in environments in which landmarks are novel, unreliable, or absent, but it also contributes to the formation of cognitive maps [4][5][6] . Understanding the neural circuits and computations supporting path integration is now a clinically relevant objective, as path integration is one of the first cognitive functions to be affected during the early stages of Alzheimer's disease 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Hippocampal firing fields anchored to a moving object predict homing direction during path-integration-based behavior

Jazi

Tymorek

Yen

et al. 2022

Preprint

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Homing based on path integration (H-PI) is a form of navigation in which an animal uses self-motion cues to keep track of its position and return to a starting point. Despite evidence for a role of the hippocampus in H-PI, the firing patterns of hippocampal neurons associated with homing performance are unknown. Here we developed a behavioral task for mice to characterize spatially selective cells during H-PI. The task required a mouse to find a variably placed lever on an arena before returning to its home base. H-PI was assessed in complete darkness. Recordings from CA1 pyramidal neurons in mice showed that several firing fields were anchored to the lever position. The spatial stability of lever-anchored fields was reduced during trials with lower homing accuracy, and the activity of a subset of lever-anchored firing fields predicted homing direction. These results demonstrate how neurons with object-anchored firing fields contribute to navigation.

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Section: Introductionmentioning

confidence: 99%

Hippocampal firing fields anchored to a moving object predict homing direction during path-integration-based behavior

Jazi

Tymorek

Yen

et al. 2022

Preprint

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“…Grid cells in the medial entorhinal cortex (MEC) fire in multiple spatial locations to form a periodic hexagonal array that spans two-dimensional space (Fyhn et al, 2004; Hafting et al, 2005; Jacobs et al, 2013). This periodic code is implicated in path integration, a cognitive function involving the integration of self-motion cues to maintain one’s sense of location relative to a starting point in space (Gil et al, 2018; McNaughton et al, 2006; Mittelstaedt & Mittelstaedt, 1980; Segen et al, 2022). Both grid cell and path integration impairments are sensitive markers of pathological decline during early AD in human subjects and mouse models of pathology (Bierbrauer et al, 2020; Coughlan et al, 2018; Kunz et al, 2015; Mucke et al, 2000; Segen et al, 2022; Ying et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…This periodic code is implicated in path integration, a cognitive function involving the integration of self-motion cues to maintain one’s sense of location relative to a starting point in space (Gil et al, 2018; McNaughton et al, 2006; Mittelstaedt & Mittelstaedt, 1980; Segen et al, 2022). Both grid cell and path integration impairments are sensitive markers of pathological decline during early AD in human subjects and mouse models of pathology (Bierbrauer et al, 2020; Coughlan et al, 2018; Kunz et al, 2015; Mucke et al, 2000; Segen et al, 2022; Ying et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Grid cell disruption in a mouse model of early Alzheimer’s disease reflects reduced integration of self-motion cues and increased influence of environmental geometry

Ying

Reboreda

Yoshida

et al. 2022

Preprint

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Grid cell impairments and path integration deficits are sensitive markers of early Alzheimer's disease (AD). Converging evidence from human and rodent studies suggest that disrupted grid coding underlies path integration deficits in preclinical individuals. However, it still remains unclear if disrupted early AD grid coding reflects increased noise across the network or a specific deficit in path integration, perhaps via an impairment in the integration of self-motion cues. Here, we report in the J20 transgenic amyloid beta mouse model of early AD that grid cells were spatially unstable towards the center of the square arena but not near the borders, had qualitatively different spatial components that aligned parallel to the borders of the environment, and exhibited impaired integration of distance travelled via reduced theta phase precession. Our results suggest that disrupted early AD grid coding reflects reduced integration of self-motion cues but not environmental landmarks, providing further evidence that grid cell impairments underlie specific path integration deficits in early AD.

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“…In line with this hypothesis, de cits in self-based navigation abilities, also speci cally involving the path integration performance, have been reported in healthy aging (Allen et al, 2004;Skolimowska et al, 2011;Xie et al, 2017), mild cognitive impairment and Alzheimer's disease (Mokrisova et al, 2016). De cits in path integration abilities have been previously associated with compromised entorhinal grid cell computations (Stangl et al, 2018), and both path integration and grid cells de cits have been proposed as sensitive biomarkers of pathological decline in early Alzheimer's disease (Segen et al, 2022;Kunz et al, 2015;Howett et al, 2019;Bierbrauer et al 2020). Egocentric heading based on path integration, moreover, has also been thought to more closely support the clinical discrimination between Alzheimer's and non-Alzheimer's dementia than navigational tasks based on allocentric, map-based knowledge (Tu et al 2017).…”

Section: Discussionmentioning

confidence: 83%

Empowering Episodic Memory through a model-based Egocentric Navigational Training

Fragueiro

Tosoni

Matteo

et al. 2022

Preprint

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Recent works have proposed that spatial mechanisms in the hippocampal-entorhinal system might have originally developed to represent distances and positions in the physical space and successively evolved to represent experience and memory in the mental space (Bellmund et al., 2018; Bottini and Doeller, 2020). Within this phylogenetic continuity hypothesis (Buzsáki and Moser, 2013), mechanisms supporting episodic and semantic memory would have evolved from egocentric and allocentric spatial navigation mechanisms, respectively. Recent studies have described a specific relationship between human performance in egocentric navigation and episodic memory (Committeri et al., 2020; Fragueiro et al., 2021), representing the first behavioral support to this hypothesis. Here, we tested the causal relationship among egocentric navigation and both episodic and semantic components of declarative memory. We conducted two experiments on healthy young adults: in the first experiment, participants were submitted to a navigational training, while in the second experiments participants completed a visual perceptual training. Performance in a set of memory tasks assessing episodic, semantic and short-term memory was compared among the pre- vs. post-training sessions. Results showed a specific, causal effect of the navigational training on episodic memory, as performance in this task, but not in semantic or in short-term memory tasks, was significantly improved in the post-training session. On the contrary, the visual perceptual training did not cause any improvement of the memory performance.Our findings do not only provide strong support to the phylogenetic continuity hypothesis between mechanisms of spatial navigation and memory but also offer insights for possible clinical applications.

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Path integration in normal aging and Alzheimer’s disease

Cited by 32 publications

References 131 publications

Hippocampal firing fields anchored to a moving object predict homing direction during path-integration-based behavior

Hippocampal firing fields anchored to a moving object predict homing direction during path-integration-based behavior

Grid cell disruption in a mouse model of early Alzheimer’s disease reflects reduced integration of self-motion cues and increased influence of environmental geometry

Empowering Episodic Memory through a model-based Egocentric Navigational Training

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