Hippocampal trace coding dominates and disrupts place coding

Abstract

The hippocampus is widely viewed as a spatial map because many CA1 neurons exhibit spatially selective activity during exploration. However, the hippocampus is also involved in nonspatial learning, including conditioning tasks. Most prior reports of nonspatial hippocampal activity were obtained in immobile animals, leading to the proposal that the hippocampus encodes spatial variables during locomotion and nonspatial variables during immobility. The question of how the hippocampus encodes both spatial and nonspatial variables during locomotion and spatial exploration has remained unanswered. To address this issue directly, we used calcium imaging to record the activity of thousands of CA1 neurons from rats tested on a conditioning task while freely exploring an open field. Across more than 6,000 neurons from five rats, the rate of calcium events increased during conditioning task periods relative to non-task periods, an effect that persisted after controlling for locomotor speed. At the single cell level, conditioning task modulation was widespread and strongly biased toward increased activity; neurons whose activity was enhanced during the conditioning task outnumbered spatially selective neurons by more than threefold. In addition, many neurons showed significantly increased activity during specific segments of the conditioning task. At the population level, conditioning coding remained invariant to changing spatial location; in contrast, spatial coding was reduced during task periods. These findings show that during active behavior, engagement in the conditioning task reorganizes hippocampal activity into a temporally structured pattern of population activity that can dominate and disrupt place coding. Together, these results challenge the view that the hippocampus functions primarily as a stable spatial map.