The vicarious nature of hippocampal theta sequences

Planning entails running simulations forward to identify possible outcomes. It is useful for situations where outcomes are uncertain, costly or dangerous to pursue. A growing body of literature is finding that during theta states in the rodent hippocampus, sequences run forward along possible futures, enabling 'episodic future thinking' that can be used within a neural circuit for planning. Emerging data suggest that the prelimbic cortex initiates these simulations, an entorhinal-hippocampal interaction generates them and valuation systems in the ventral striatum (nucleus accumbens) and orbitofrontal cortex evaluate them, enabling downstream decision-making processes to take action. Within the hippocampus, each theta cycle carries activity representing the present followed by explorations of possible paths ahead of the animal. These representations occur serially and sequentially. These theta sweeps are not mere reflections of movement but dynamic cognitive simulations whose length, direction and content shift with learning, confidence and experience. Individual theta cycles change in length and representation from cycle to cycle, suggesting a cognitive role. In this review, we bring together that body of literature and identify open questions and controversies for future research, including questions regarding how sweeps are structured, how they shift between exploration and commitment, and how threat-related representations interface with avoidance circuits. This article is part of the theme issue 'The role of hippocampal predictions in cognition: bridging perception and memory'.