Skipping ahead: A circuit for representing the past, present, and future

Abstract

Envisioning the future is intuitively linked to our ability to remember the past. Within the memory system, substantial work has demonstrated the involvement of the prefrontal cortex and the hippocampus in representing the past and present. Recent data shows that both the prefrontal cortex and the hippocampus encode future trajectories, which are segregated in time by alternating cycles of the theta rhythm. Here, we discuss how information is temporally organized by these brain regions supported by the medial septum, nucleus reuniens, and parahippocampal regions. Finally, we highlight a brain circuit that we predict is essential for the temporal segregation of future scenarios.

Keywords: cycle skipping; hippocampus; memory; neuroscience; prefrontal cortex; theta sequences.

Figure 1.. Direct and indirect pathways connecting the medial prefrontal cortex (mPFC) and the hippocampus.

(A) Monosynaptic pathways between the both dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) and prelimbic (PL) and infralimbic subregions of the mPFC with an anatomical overview of parahippocampal areas including presubiculum (PrS), parasubiculum (PaS), perirhinal (PER), and the postrhinal cortex (POR). (Bi) Bidirectional indirect pathways between the mPFC hippocampus passing through the PER and medial and lateral entorhinal cortices (MEC, LEC). (Bii) Bidirectional indirect mPFC-hippocampus pathway connecting through the nucleus reuniens (NRe).

Figure 2.. Alternating theta cycles provide a framework for imagining or deliberating between future options.

(A) Diagram of the hippocampal formation with examples different cell types recorded across the hippocampus and the medial entorhinal cortex (MEC). (B) Hippocampal time cell sequences in relation to hippocampal theta (above) and during septal inactivation (below). (C) Hippocampal place cell sequences in relation to hippocampal theta (above) and during septal inactivation (below).

Figure 3.. Alternating theta cycles provide a framework for alternate representations of future options.

(A) Head direction cell assemblies on alternating theta cycles recorded in the medial entorhinal cortex (MEC). (B) From inputs received from the MEC may support theta sequences of upcoming potential paths on alternating theta cycles.

Figure 4.. Proposed circuit for representation of future scenarios.

The medial prefrontal cortex (mPFC) and nucleus reuniens (NRe) provide unique input to the pre- and parasubiculum, and medial entorhinal cortex on alternating theta cycles. The pre- and parasubiculum and the medial entorhinal cortex (MEC) represent head directions to the animal’s right and left on alternating theta cycles. In turn, these inputs drive the expression of alternating theta sequences that map out future scenarios in both the hippocampus and mPFC.