Summary Recent evidence suggests that the hippocampus may integrate overlapping memories into relational representations, or schemas, that link indirectly related events and support flexible memory expression. Here we explored the nature of hippocampal neural population representations for multiple features of events and the locations and contexts in which they occurred. Hippocampal networks developed hierarchical organizations of associated elements of related but separately acquired memories within a context, and distinct organizations for memories where the contexts differentiated object-reward associations. These findings reveal neural mechanisms for the development and organization of relational representations.

Summary Excitatory control of inhibitory neurons is poorly understood due to the difficulty of studying synaptic connectivity in vivo. We inferred such connectivity through analysis of spike timing and validated this inference using juxtacellular and optogenetic control of presynaptic spikes in behaving mice. We observed that neighboring CA1 neurons had stronger connections, and that superficial pyramidal cells projected more to deep interneurons. Connection probability and strength were skewed, with a minority of highly connected hubs. Divergent presynaptic connections led to synchrony between interneurons. Synchrony of convergent presynaptic inputs boosted postsynaptic drive. Presynaptic firing frequency was read out by postsynaptic neurons through short-term depression and facilitation, with individual pyramidal cells and interneurons displaying a diversity of spike transmission filters. Additionally, spike transmission was strongly modulated by prior spike timing of the postsynaptic cell. These results bridge anatomical structure with physiological function.

Most studies on memory consolidation consider the new information as if it were imposed on a tabula rasa, but considerable evidence indicates that new memories must be interleaved within a large network of relevant pre-existing knowledge. Early studies on reconsolidation highlighted that a newly consolidated memory could be erased after reactivation, but new evidence has shown that an effective reactivation experience must also involve memory re-organization to incorporate new learning. The combination of these observations on consolidation and reconsolidation highlight the fundamental similarities of both phenomena as integration of new information on old, and suggest that reconsolidation = consolidation as a never-ending process of schema modification. Memories evolve over time, and many have come to consider that memories have two extended “lives” following the initial encoding of new information. The first, called consolidation, involves a prolonged period after learning when new information becomes fixed at a cellular level and interleaved among already existing memories to enrich our body of personal and factual knowledge. The second, called reconsolidation, turns the tables on a memory and involves the converse process in which a newly consolidated memory is now subject to modification though subsequent reminders and interference. Here we propose that the time has come to join the literatures on these two lives of memories, towards the goal of understanding memory as an ever-evolving organization of the record of experience.

The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequencememory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as "in sequence" or "out of sequence". We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items-in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe-specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20 -40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4 -12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus.