Time–place learning over a lifetime: absence of memory loss in trained old mice

Abstract

Time -place learning (TPL) offers the possibility to study the functional interaction between cognition and the circadian system with aging. With TPL, animals link biological significant events with the location and the time of day. This whatwhere-when type of memory provides animals with an experience-based daily schedule. Mice were tested for TPL five times throughout their lifespan and showed (re)learning from below chance level at the age of 4, 7, 12, and 18 mo. In contrast, at the age of 22 mo these mice showed preservation of TPL memory (absence of memory loss), together with deficiencies in the ability to update time-of-day information. Conversely, the majority of untrained (na€ ıve) mice at 17 mo of age were unable to acquire TPL, indicating that training had delayed TPL deficiencies in the mice trained over lifespan. Two out of seven na€ ıve mice, however, compensated for correct performance loss by adapting an alternative learning strategy that is independent of the age-deteriorating circadian system and presumably less cognitively demanding. Together, these data show the age-sensitivity of TPL, and the positive effects of repeated training over a lifetime. In addition, these data shed new light on aging-related loss of behavioral flexibility to update time-of-day information.

Role of Aging and Hippocampus in Time-Place Learning: Link to Episodic-Like Memory?

“…CD1 mice were not studied because (a) none of the CD1 mice mastered the 3-arm TPL task and (b) CD1 mice mastering the 2-arm TPL task did not use a circadian but instead an ordinal (non-circadian) strategy. Likewise aged C57Bl/6 mice are unable to master the 3-arm TPL task, unless they were trained in this task earlier in their life (Mulder et al, 2015 ).…”

“…Previously, we investigated TPL for the first time in the context of aging (Mulder et al, 2015 ). We found that most untrained C57Bl/6 mice were unable to acquire TPL at middle-age (17 months).…”

“…We hypothesize that age-related hippocampal dysfunction, together with age-related circadian system decline caused these untrained mice to adapt this ordinal (non-circadian) TPL strategy, which is presumably less cognitively demanding than cTPL (Mulder et al, 2013a ). In contrast, mice trained over their lifespan successfully maintained the circadian strategy (cTPL, learned at young age) until old age (Mulder et al, 2015 ). At this age however, mice showed signs of behavioral rigidity and a lack to update TOD information.…”

“…The used TPL test apparatus and testing procedures were described before (Figure 5A , 3-arm TPL design; Van der Zee et al, 2008 ; Mulder et al, 2013a , b , 2014 , 2015 ). Briefly, to induce food seeking behavior and voluntary location-choices, mice were food deprived to 85% of their ad libitum body weight, as individually determined by the average of three daily measurements prior to initiating food deprivation.…”

Aprendizaje de tiempo y lugar: efectos de la duración del período de disponibilidad y de la variabilidad o constancia de la secuencia de locaciones

“…Se cree que esta diferencia en parámetros promueve diferencias en el tipo de estrategia de estimación temporal que describe mejor los resultados obtenidos (Crystal, 2009). Se ha encontrado que las tareas de TPL diario involucran timing circadiano (Mulder, Gerkema, & Van der Zee, 2013;Mulder, Reckman, Gerkema, & Van der Zee, 2015), mientras que en TPL intervalar se aducen mecanismos intervalares de estimación temporal (Crystal, 2009;García-Gallardo & Carpio, 2016;Thorpe et al, 2007;Thorpe, Petrovic, & Wilkie, 2002).…”