Tracing a Path for Memory in the Hippocampus

Abstract

The hippocampal activity supporting trace fear conditioning has long been mysterious, but a leading hypothesis posits "time-cell"-like sequential patterns. In this issue of Neuron, Ahmed et al. (2020) present new data suggesting that, at least during the first session of learning, a subset of neurons coalesce to selectively encode the task but without expressing reliable sequences.

In trace conditioning paradigms, a sensory cue (the “conditioned stimulus”, CS+) is associated with with an aversive stimulus (“unconditioned stimulus”, US) that is administered after some delay from the end of the cue (the trace period). On some trials, a different, safe cue (CS−) is given. Longer delays during the trace period make learning this association hippocampally-dependent, but the pattern of ensemble neural activity which supports the learning has been unknown. (Top) Most theories had postulated that sequences of activity expressed by “time cells” might allow animals to bridge from CS to the US. (Bottom) Ahmed and colleagues (2020) show that, following learning, ensemble activity encodes the stages of the task but hippocampal neurons do not express expected sequential activity. This suggests that during the initial stages of learning, coarse behavioral responses (withholding licking in this case) do not require sequences of hippocampal activity. Perhaps later, after behavioral responses eventually become more precise, these sequences might emerge.