Hippocampal place cell remapping occurs with memory storage of aversive experiences

Aversive stimuli can cause hippocampal place cells to remap their firing fields, but it is not known whether remapping plays a role in storing memories of aversive experiences. Here, we addressed this question by performing in vivo calcium imaging of CA1 place cells in freely behaving rats (n = 14). Rats were first trained to prefer a short path over a long path for obtaining food reward, then trained to avoid the short path by delivering a mild footshock. Remapping was assessed by comparing place cell population vector similarity before acquisition versus after extinction of avoidance. Some rats received shock after systemic injections of the amnestic drug scopolamine at a dose (1 mg/kg) that impaired avoidance learning but spared spatial tuning and shock-evoked responses of CA1 neurons. Place cells remapped significantly more following remembered than forgotten shocks (drug-free versus scopolamine conditions); shock-induced remapping did not cause place fields to migrate toward or away from the shocked location and was similarly prevalent in cells that were responsive versus non-responsive to shocks. When rats were exposed to a neutral barrier rather than aversive shock, place cells remapped significantly less in response to the barrier. We conclude that place cell remapping occurs in response to events that are remembered rather than merely perceived and forgotten, suggesting that reorganization of hippocampal population codes may play a role in storing memories for aversive events. eLife digestThe human brain is able to remember experiences that occurred at specific places and times, such as a birthday party held at a particular restaurant. A part of the brain known as the hippocampus helps to store these episodic memories, but how exactly is not fully understood.Within the hippocampus are specialized neurons known as place cells which 'label' locations with unique patterns of brain activity. When we revisit a place, such as the restaurant, place cells recall the stored pattern of brain activity allowing us to recognize the familiar location.It has been shown that a new negative experience at a familiar place - for example, if we went back to the restaurant and had a terrible meal - triggers place cells to update the brain activity label associated with the location. However, it remains uncertain whether this re-labelling assists in storing the memory of the unpleasant experience.To investigate, Blair et al. used a technique known as calcium imaging to monitor place cells in the hippocampus of freely moving rats. The rats were given a new experience - a mild foot shock - at a previously explored location. Tiny cameras attached to their heads were then used to record the activity of hundreds of place cells before and after the shock.Initially, the rats remembered the aversive experience and avoided the location where they had been shocked. Over time, the rats began to return to the location; however, their place cells displayed different patterns of activity compared to their previous visits before the shock.To test whether this change in place cell activity corresponded with new memories, another group of rats were administered a mild amnesia-inducing drug before the shock, causing them to forget the experience. These rats did not avoid the shock site or show any changes in place cell activity when they revisited it.These findings imply that new events cause place cells to alter their 'label' for a location only if the event is remembered, not if it is forgotten. This indicates that alterations in place cell activity patterns may play a role in storing memories of unpleasant experiences. Having a better understanding of how episodic memories are stored could lead to better treatments for diseases that impair memory, such as Alzheimer's disease and age-related dementia.