Long-Term Stabilization of Place Cell Remapping Produced by a Fearful Experience

Abstract

Fear is an emotional response to danger that is highly conserved throughout evolution because it is critical for survival. Accordingly, episodic memory for fearful locations is widely studied using contextual fear conditioning, a hippocampus-dependent task (Kim and Fanselow, 1992; Phillips and LeDoux, 1992). The hippocampus has been implicated in episodic emotional memory and is thought to integrate emotional stimuli within a spatial framework. Physiological evidence supporting the role of the hippocampus in contextual fear indicates that pyramidal cells in this region, which fire in specific locations as an animal moves through an environment, shift their preferred firing locations shortly after the presentation of an aversive stimulus (Moita et al., 2004). However, the long-term physiological mechanisms through which emotional memories are encoded by the hippocampus are unknown. Here we show that during and directly after a fearful experience, new hippocampal representations are established and persist in the long term. We recorded from the same place cells in mouse hippocampal area CA1 over several days during predator odor contextual fear conditioning and found that a subset of cells changed their preferred firing locations in response to the fearful stimulus. Furthermore, the newly formed representations of the fearful context stabilized in the long term. Our results demonstrate that place cells respond to the presence of an aversive stimulus, modify their firing patterns during emotional learning, and stabilize a long-term spatial representation in response to a fearful encounter. The persistent nature of these representations may contribute to the enduring quality of emotional memories.

Precise spatial coding is preserved along the longitudinal hippocampal axis

“…Thus, similar alterations in firing rate in the VH may code for emotional valence. Interestingly, even though the mildly anxiogenic cues used in this study did not produce changes in firing rate in the DH, previous studies have shown that very strong emotional cues do lead to increases in firing rate in the DH (Moita et al, ; Wang et al, ). Therefore, it is possible that responsiveness to emotional cues is not exclusive to the VH, and that there exists an emotional processing gradient along the hippocampal axis.…”

“…Distance estimation can be critical for planning and goal‐directed navigation, and evidence of this function and its segregation along the longitudinal hippocampal axis has been reported in humans (Morgan et al, ). Given that the hippocampus integrates many aspects of episodic memory, including spatial and nonspatial events such as emotional and motivational information (Wood et al, ; Moita et al, ; Kennedy and Shapiro, ; Wang et al, ), it is likely that the purpose of the redundant spatial gradient along the longitudinal hippocampal axis is multifaceted. This work highlights the existence and importance of precise spatial coding as a critical determinant of activity along the longitudinal axis.…”

Hippocampal CA2 Activity Patterns Change over Time to a Larger Extent than between Spatial Contexts

“…Although there is no theoretical reason why temporal coding with repeated sequences would be limited to a particular time scale, it is likely that sequential neuronal activity on a much longer time scale would require different underlying cellular and circuit mechanisms than the sequential activation of CA1 cells over much shorter intervals. In contrast to a mechanism that relies on fixed sequences to be informative about elapsed time, it is also feasible that the time-varying neuronal firing patterns do not become informative by direct repetition during memory recall, but that it is rather a transition from changing to fixed neuronal firing patterns that supports memory, as has been suggested for neuronal activity in the mouse CA1 subregion (Kentros et al, 2004; Wang et al, 2012). …”

Still searching for the engram

“…In yet another task, remapping was observed when rats switched between start and goal arms while performing the same spatial memory task in the same maze (Bahar et al, 2011). In parallel with these studies, remapping also occurs when a neutral environment is made aversive by fear conditioning (Wang et al, 2012). Taken together, these studies show in a variety of ways that distinct memories govern the organization of the hippocampal map of the environment in which specific events must be remembered.…”