Hippocampal ensembles represent sequential relationships among an extended sequence of nonspatial events

Babak Shahbaba,Lingge Li,Pierre Baldi,Derenik Haghverdian,Keiland W Cooper,Mansi Saraf,Forest Agostinelli,Gabriel A Elias,Norbert J Fortin

doi:10.1038/s41467-022-28057-6

Abstract

The hippocampus is critical to the temporal organization of our experiences. Although this fundamental capacity is conserved across modalities and species, its underlying neuronal mechanisms remain unclear. Here we recorded hippocampal activity as rats remembered an extended sequence of nonspatial events unfolding over several seconds, as in daily life episodes in humans. We then developed statistical machine learning methods to analyze the ensemble activity and discovered forms of sequential organization and coding important for order memory judgments. Specifically, we found that hippocampal ensembles provide significant temporal coding throughout nonspatial event sequences, differentiate distinct types of task-critical information sequentially within events, and exhibit theta-associated reactivation of the sequential relationships among events. We also demonstrate that nonspatial event representations are sequentially organized within individual theta cycles and precess across successive cycles. These findings suggest a fundamental function of the hippocampal network is to encode, preserve, and predict the sequential order of experiences.

Highlights

The hippocampus is critical to the temporal organization of our experiences
We found that hippocampal ensembles provided significant temporal information during individual stimulus presentations, which was primarily stimulus-specific and reflected sequential relationships among stimuli through a temporal lag effect, and that this temporal coding extended across the full sequence of stimuli unfolding over several seconds
We trained rats to perform a nonspatial sequence memory task, which shows strong behavioral correspondence in rats and humans[25]. This task involves repeated presentations of sequences of odors in a common odor port and requires subjects to determine whether each odor is presented “in sequence” (InSeq; e.g., ABC...) or “out of sequence” (OutSeq; e.g., ABD...) to receive a water reward (Fig. 1a). This InSeq/OutSeq judgment is performed on a trialby-trial basis, such that each correctly identified odor was followed by a reward and an incorrect response resulted in early termination of the sequence

Summary

Introduction

The hippocampus is critical to the temporal organization of our experiences. this fundamental capacity is conserved across modalities and species, its underlying neuronal mechanisms remain unclear. Using a simpler decoding model with a higher temporal resolution, we found that these sequential relationships can even be compressed within a single theta cycle, that the information represented by individual neurons precessed across cycles, and confirmed the sequential reactivation pattern within trials observed with the previous model These results suggest a fundamental function of the hippocampus is to simultaneously represent the sequential order of experience in real-time, including internal representations of the temporal context of events and of different forms of task-critical information, and at a higher level of abstraction, including temporally compressed representations extracting task-critical sequential relationships among events separated in time by several seconds. These findings are consistent with, and provide potential neuronal mechanisms for, the critical role of the hippocampus in temporally organizing our past experiences and future behavior

Methods

Results

Conclusion