A Theory of Hippocampal Theta Correlations

Hippocampal place cell sequences have been hypothesized to serve as diverse purposes as the induction of synaptic plasticity, formation and consolidation of long-term memories, or navigation and planning. During spatial behaviors of rodents, sequential firing of place cells at the theta timescale (known as theta sequences) encodes running trajectories, which can be considered as 1-dimensional behavioral sequences of traversed locations. In a 2-dimensional space, however, each single location can be visited along arbitrary 1-dimensional running trajectories. Thus, a place cell will generally take part in multiple different theta sequences, raising questions about how this 2-dimensional topology can be reconciled with the idea of hippocampal sequences underlying memory of (1-dimensional) episodes. Here, we propose a computational model of cornu ammonis 3 (CA3) and dentate gyrus (DG), where sensorimotor input drives the direction-dependent (extrinsic) theta sequences within CA3 reflecting the 2-dimensional spatial topology, whereas the in-trahippocampal CA3-DG projections concurrently produce intrinsic sequences that are independent of the specific running trajectory. Consistent with experimental data, these intrinsic theta sequences are less prominent in the theta state, but we show that they can nevertheless be detected during theta activity, thereby serving as running-direction independent landmark cues. We hypothesize that the intrinsic sequences largely reflect replay and preplay activity during non-theta states.