Time or place? Dissociation between object-in-place and relative recency in young APPswe/PS1dE9 mice.

Abstract

This study tests the predictions of a novel analysis of recognition memory based on a theory of associative learning, according to which recognition comprises two independent underlying processes, one relying on the to-be-recognised item having been experienced recently (self-generated priming), and the other on it being predicted by some other stimulus (retrieval-generated priming). A single experiment examined recognition performance in the APPswe/PS1dE9 (APP/PS1) mouse, a double-transgenic model of Alzheimer's disease, and wild-type (WT) littermates.Performance on two variants of the spontaneous object recognition (SOR ) was compared in 5-month-old APPswe/PS1dE9 (APP/PS1) mice, a double-transgenic model of Alzheimer's disease, and their wild-type (WT) littermates, using junk objects. In the relative recency task animals were exposed to object A, and then object B, followed by a test with both A and B. In the object-in-place task the mice were exposed to both A and B, and then tested with two copies of A, occupying the same positions as the preeexposed objects. The WT mice showed a preference for exploring the first-presented object A in the relative recency task, and the copy of A in the 'wrong' position (i.e. the one placed where B had been during the preexposure phase) in the object-in-place task. The APP/PS1 mice performed like the WT mice in the relative recency task, but showed a selective impairment in the object-in-place task. We interpret these findings in terms of Wagner's (1981) theory of associative learning, SOP, as a selective deficit in retrieval-generated priming.

Intermediate CA1 is Required for Object-in-Place Recognition Memory in Mice

“…To determine the neural correlates of OiP memory in mice, we first needed to establish a robust behavioral protocol to assess this type of recognition memory. Given our previous experience in running spontaneous recognition memory tasks using the C57/129J strain (Cruz-Sanchez et al, 2020; Inayat et al, 2021), we started by testing independent cohorts of C57/129J mice in the most common versions of the OiP recognition memory task (Ricceri et al, 1997, 2000; Dix and Aggleton, 1999; Calamandrei et al, 2002c; Barker and Warburton, 2008, 2015; Langston and Wood, 2010; Ainge et al, 2012; Davis et al, 2013; Ameen-Ali et al, 2015; Lesburguères et al, 2017; Sobin et al, 2017; Barker et al, 2017; Bonardi et al, 2021), spanning four (Dix and Aggleton, 1999; Barker and Warburton, 2008, 2015; Ameen-Ali et al, 2015; Benn et al, 2016; Barker et al, 2017; Lesburguères et al, 2017) to two objects (Langston and Wood, 2010; Langston et al, 2010b; Ainge et al, 2012; Davis et al, 2013; Ameen-Ali et al, 2015; Bonardi et al, 2021), as well as one to two sample phases (Ricceri et al, 1997, 2000; Calamandrei et al, 2002c, 2002a; Sobin et al, 2017).…”

“…In the 5-minute sample phase, mice interacted with four different objects (pyramid, dome, step, and icosahedron), after which animals were removed and placed back into their home cage (Howland et al, 2012; Barker and Warburton, 2015). After a delay of 5 minutes (Barker et al, 2007; Barker and Warburton, 2008; Reichelt et al, 2015; Bonardi et al, 2021), mice underwent a 3-minute test phase (Dix and Aggleton, 1999; Barker et al, 2007, 2017; Barker and Warburton, 2008; Tsokas et al, 2016; Lesburguères et al, 2017) in which they were placed in the chamber with the same four objects, two of which had switched location. The displaced two-object combination was counterbalanced to ensure that all six possible combinations were utilized between animals (Lesburguères et al, 2017).…”

“…Object identity and location combinations were counterbalanced across animals. After a 5-minute delay (Davis et al, 2013; Bonardi et al, 2021), animals underwent a 3-minute test phase (Davis et al, 2013) in which they were placed in the chamber with two copies of the same object (two domes or two steps). Object type and novelty side (right vs left) at the test phase were also counterbalanced.…”

“…OiP recognition memory refers to the ability to recall an association between a previously encountered object and its specific location. Importantly, object-location association memory deficits are seen in people with schizophrenia (Wood et al, 2002;Burglen et al, 2004;Wout et al, 2006), and OiP memory deficits are reported in rodent models of neurodevelopmental and neurodegenerative disorders (Howland et al, 2012;Connors et al, 2014;Ballendine et al, 2015;Bonardi et al, 2016Bonardi et al, , 2021Hall et al, 2016;Kentner et al, 2016).…”

Adding the neuro to cognition: from food storing to nest building

“…There have since been enthusiastic searches for episodic-like memory, which have resulted in serious consideration of experimental designs and of types of memory (e.g. Babb and Crystal 2005 ; Bonardi et al 2021 ; Eacott and Norman 2004 ; Feeney et al 2009 ; Zhou and Crystal 2011 ). Some of these involve what-where-when memories, others what-where-which memories, leading to the discovery that a wide range of animals, in the wild as well as in the laboratory, can integrate all or some of the components of episodic-like memory (e.g.…”