The spontaneous location recognition task for assessing spatial pattern separation and memory across a delay in rats and mice

Reichelt, Amy C.; Kramar, Cecilia P.; Ghosh-Swaby, Olivia R.; Sheppard, Paul A. S.; Kent, Brianne A.; Bekinschtein, Pedro; Saksida, Lisa M.; Bussey, Timothy J.

doi:10.1038/s41596-021-00627-w

Cited by 18 publications

(19 citation statements)

References 61 publications

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“…In addition, the two studies also differed in the strain of rats used: Hunsaker and Kesner (2008) used Long Evans rats and we used Wistar strain, which could also contribute to the observed variability (Andrews et al, 1995). Nevertheless, to the best of our knowledge, this is the first time in which the successful discrimination of displaced objects was associated with high but not low spatial displacements in rats (but see also Reichelt et al, 2021).…”

Section: Discussionmentioning

confidence: 97%

Theta and gamma oscillations in the rat hippocampus support the discrimination of object displacement in a recognition memory task

Neves

Lobão-Soares

Araujo

et al. 2022

Front. Behav. Neurosci.

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Episodic memory depends on the recollection of spatial and temporal aspects of past experiences in which the hippocampus plays a critical role. Studies on hippocampal lesions in rodents have shown that dentate gyrus (DG) and CA3 are necessary to detect object displacement in memory tasks. However, the understanding of real-time oscillatory activity underlying memory discrimination of subtle and pronounced displacements remains elusive. Here, we chronically implanted microelectrode arrays in adult male Wistar rats to record network oscillations from DG, CA3, and CA1 of the dorsal hippocampus while animals executed an object recognition task of high and low spatial displacement tests (HD: 108 cm, and LD: 54 cm, respectively). Behavioral analysis showed that the animals discriminate between stationary and displaced objects in the HD but not LD conditions. To investigate the hypothesis that theta and gamma oscillations in different areas of the hippocampus support discrimination processes in a recognition memory task, we compared epochs of object exploration between HD and LD conditions as well as displaced and stationary objects. We observed that object exploration epochs were accompanied by strong rhythmic activity in the theta frequency (6–12 Hz) band in the three hippocampal areas. Comparison between test conditions revealed higher theta band power and higher theta-gamma phase-amplitude coupling in the DG during HD than LD conditions. Similarly, direct comparison between displaced and stationary objects within the HD test showed higher theta band power in CA3 during exploration of displaced objects. Moreover, the discrimination index between displaced and stationary objects directly correlated with CA1 gamma band power in epochs of object exploration. We thus conclude that theta and gamma oscillations in the dorsal hippocampus support the successful discrimination of object displacement in a recognition memory task.

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Section: Discussionmentioning

confidence: 97%

Theta and gamma oscillations in the rat hippocampus support the discrimination of object displacement in a recognition memory task

Neves

Lobão-Soares

Araujo

et al. 2022

Front. Behav. Neurosci.

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“…Alternatively, this could be tested with a behavioral pattern separation task that can be performed over a few days (spontaneous location recognition or object lure discrimination and mnemonic discrimination testing) rather than a month (the present work). Using a more condensed behavioral pattern separation task would also enable future dissociation of the stages of learning (encoding, consolidation, and retrieval) and factors that regulate each stage (Bekinschtein et al, 2013;Johnson et al, 2018;Morales et al, 2021;Reichelt et al, 2021). (Yassa et al, 2010;Stone et al, 2011;Wilson et al, 2013;Hansen et al, 2018;Yun et al, 2018b;Amani et al, 2021), antidepressant-like behavior (Yun et al, 2018a), and reward-seeking (Ge et al, 2017) (Schultz, 1997;Ungless et al, 2010;Morikawa and Paladini, 2011;Marinelli and McCutcheon, 2014;Keiflin and Janak, 2015;Wise and Jordan, 2021), and S%&$%&3!2"##&3&/$!-.967!+3!-.9%"44+('F4'0!("3(:"$1!'3&!&/<'<&2!:/2&3!…”

Section: Discussionmentioning

confidence: 99%

Behavioral pattern separation and cognitive flexibility are enhanced in a mouse model of increased lateral entorhinal cortex-dentate gyrus circuit activity

Yun

Soler

Tran

et al. 2023

Preprint

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Behavioral pattern separation and cognitive flexibility are essential cognitive abilities which are disrupted in many brain disorders. Better understanding of the neural circuitry involved in these abilities will open paths to treatment. In humans and mice, discrimination and adaptation rely on integrity of the hippocampal dentate gyrus (DG) which both receive glutamatergic input from the entorhinal cortex (EC), including the lateral EC (LEC). Inducible increase of EC-DG circuit activity improves simple hippocampal-dependent associative learning and increases DG neurogenesis. Here we asked if the activity of LEC fan cells that directly project to the DG (LEC→DG neurons) regulates behavioral pattern separation or cognitive flexibility. C57BL6/J male mice received bilateral LEC infusions of a virus expressing shRNA TRIP8b, an auxiliary protein of an HCN channel or a control virus (SCR shRNA); this approach increases the activity of LEC→DG neurons. Four weeks later, mice underwent testing for behavioral pattern separation and reversal learning (touchscreen-based Location Discrimination Reversal [LDR] task) and innate fear of open spaces (elevated plus maze [EPM]) followed by counting of new DG neurons (doublecortin-immunoreactive cells [DCX+] cells). TRIP8b and SCR shRNA mice performed similarly in general touchscreen training and LDR training. However, in late LDR testing, TRIP8b shRNA mice reached the first reversal more quickly and had more accurate discrimination vs. SCR shRNA mice, specifically when pattern separation was challenging (lit squares close together or small separation). Also, TRIP8b shRNA mice achieved more reversals in late LDR testing vs. SCR shRNA mice. Supporting a specific influence on cognitive behavior, SCR shRNA and TRIP8b shRNA mice did not differ in total distance traveled or in time spent in the closed arms of the EPM. Supporting an inducible increase in LEC-DG activity, DG neurogenesis was increased. These data indicate TRIP8b shRNA mice had better pattern separation and reversal learning and more neurogenesis vs. SCR shRNA mice. This work advances fundamental and translational neuroscience knowledge relevant to two cognitive functions critical for adaptation and survival —behavioral pattern separation and cognitive flexibility — and suggests the activity of LEC→DG neurons merits exploration as a therapeutic target to normalize dysfunctional DG behavioral output.

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“…Similarly to the smart-Kage clustering above, these thresholds were selected to assign a maximum number of control animals into a single ‘control’ cluster. Animals with T-maze performance below 70%; the absolute value of NOR d2 ratio 29 below 0.04 and the absolute value of OPR d2 ratio below 0.06 were identified as displaying cognitive decline. In brief, d2 ratio is the difference in exploration time between the novel and familiar object, normalized with regard to their combined exploration time.…”

Section: Methodsmentioning

confidence: 99%

A novel fully-automated system for lifelong continuous phenotyping of mouse cognition and behaviour

Kejzar

Sasaguri

et al. 2022

Preprint

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Comprehensive ethologically-relevant behavioural phenotyping in rodent experiments is essential for deciphering the neural basis of animal cognition. Automated home-cage monitoring systems present a valuable tool to fulfil this need. However, they often involve complex animal training routines, water or food deprivation, and probe a limited range of behaviours. Here, we present a new fully automated AI-driven home-cage system for cognitive and behavioural phenotyping in mice. The system incorporates spontaneous alternation T-maze, novel-object recognition and object-in-place recognition tests combined with monitoring of an animal position, water consumption, quiescence and locomotion patterns, all carried out continuously and simultaneously in an unsupervised fashion over long periods of time. Mice learnt the tasks rapidly without any need for water or food restrictions. We applied ethomics approach to show that combined statistical properties of multiple behaviours can be used to discriminate between mice with hippocampal, medial entorhinal and sham lesions and accurately predict genotype of Alzheimer disease mouse models on an individual animal level, surpassing the performance of several gold standard cognitive tests. This technology could enable large-scale behavioural screening for genes and neural circuits underlying spatial memory and other cognitive processes.

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The spontaneous location recognition task for assessing spatial pattern separation and memory across a delay in rats and mice

Cited by 18 publications

References 61 publications

Theta and gamma oscillations in the rat hippocampus support the discrimination of object displacement in a recognition memory task

Theta and gamma oscillations in the rat hippocampus support the discrimination of object displacement in a recognition memory task

Behavioral pattern separation and cognitive flexibility are enhanced in a mouse model of increased lateral entorhinal cortex-dentate gyrus circuit activity

A novel fully-automated system for lifelong continuous phenotyping of mouse cognition and behaviour

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