Systems consolidation impairs behavioral flexibility

Abstract

Behavioral flexibility is important in a changing environment. Previous research suggests that systems consolidation, a longterm poststorage process that alters memory traces, may reduce behavioral flexibility. However, exactly how systems consolidation affects flexibility is unknown. Here, we tested how systems consolidation affects: (1) flexibility in response to value changes and (2) flexibility in response to changes in the optimal sequence of actions. Mice were trained to obtain food rewards in a Y-maze by switching nose pokes between three arms. During initial training, all arms were rewarded and mice simply had to switch arms in order to maximize rewards. Then, after either a 1 or 28 d delay, we either devalued one arm, or we reinforced a specific sequence of pokes. We found that after a 1 d delay mice adapted relatively easily to the changes. In contrast, mice given a 28 d delay struggled to adapt, especially for changes to the optimal sequence of actions. Immediate early gene imaging suggested that the 28 d mice were less reliant on their hippocampus and more reliant on their medial prefrontal cortex. These data suggest that systems consolidation reduces behavioral flexibility, particularly for changes to the optimal sequence of actions.

Developmental emergence of persistent memory for contextual and auditory fear in mice

“…Several studies point to hippocampal maturation as a major factor in guiding the onset of fear memory persistence, likely by enabling the long-term retrieval of infant memories. Furthermore, our data show that a correlate of remote memory retrieval, activation of the prefrontal cortex (Takehara et al 2003;Frankland et al 2004a;Frankland and Bontempi 2005;Vetere et al 2011;Wheeler et al 2013;Kitamura et al 2017;DeNardo et al 2019;Grella et al 2020;Pan et al 2020;Sathiyakumar et al 2020), is absent for infant memories. Interestingly, Guskjolen et al (2018) found that adult retrieval of P17 memories through optogenetic manipulation of hippocampal neuronal ensembles reinstated patterns of neuronal activity in brain regions such as the entorhinal cortex, but not PL.…”

“…While studies have implicated developmental changes in the hippocampus in infantile forgetting ( Akers et al 2014 ; Guskjolen et al 2018 ; Travaglia et al 2018 ), much less is known about the contribution of other brain areas involved in remote memory, such as the prefrontal cortex ( Takehara et al 2003 ; Frankland et al 2004a ; Frankland and Bontempi 2005 ; Vetere et al 2011 ; Wheeler et al 2013 ; Kitamura et al 2017 ; DeNardo et al 2019 ; Grella et al 2020 ; Pan et al 2020 ; Sathiyakumar et al 2020 ), in this process. In adult rodents, recruitment of neuronal activity in the prelimbic cortex (PL) has been shown to occur following remote, but not recent, fear memory retrieval (Frankland et al 2004a; Wheeler et al 2013 ; DeNardo et al 2019 ; Grella et al 2020 ).…”

“…processing (Takehara et al 2003;Frankland and Bontempi 2005;Vetere et al 2011;Wheeler et al 2013;Bergstrom 2016;Kitamura et al 2017;Sathiyakumar et al 2020). Nevertheless, the contribution of brain regions beyond the hippocampus to the remote recall of memories acquired in early life has not been examined.…”

“…Importantly, as memory tasks differ in their brain circuit requirements, it is conceivable that the onset of memory persistence may vary even between cognate behavioral tasks. As our knowledge of the synaptic, cellular, and systems bases of remote memory formation continues to be challenged and updated ( Albo and Gräff 2018 ), a significant body of research implicates brain regions such as the prefrontal cortex and amygdala in adult remote memory processing ( Takehara et al 2003 ; Frankland and Bontempi 2005 ; Vetere et al 2011 ; Wheeler et al 2013 ; Bergstrom 2016 ; Kitamura et al 2017 ; Sathiyakumar et al 2020 ). Nevertheless, the contribution of brain regions beyond the hippocampus to the remote recall of memories acquired in early life has not been examined.…”