Coordinated Emergence of Hippocampal Replay and Theta Sequences during Post-natal Development

Abstract

Summary Hippocampal place cells encode an animal’s current position in space during exploration [ 1 ]. During sleep, hippocampal network activity recapitulates patterns observed during recent experience: place cells with overlapping spatial fields show a greater tendency to co-fire (“reactivation”) [ 2 ], and temporally ordered and compressed sequences of place cell firing observed during wakefulness are reinstated (“replay”) [ 3 , 4 , 5 ]. Reactivation and replay may underlie memory consolidation [ 6 , 7 , 8 , 9 , 10 ]. Compressed sequences of place cell firing also occur during exploration: during each cycle of the theta oscillation, the set of active place cells shifts from those signaling positions behind to those signaling positions ahead of an animal’s current location [ 11 , 12 ]. These “theta sequences” have been linked to spatial planning [ 13 ]. Here, we demonstrate that, before weaning (post-natal day [P]21), offline place cell activity associated with sharp-wave ripples (SWRs) reflects predominantly stationary locations in recently visited environments. By contrast, sequential place cell firing, describing extended trajectories through space during exploration (theta sequences) and subsequent rest (replay), emerge gradually after weaning in a coordinated fashion, possibly due to a progressive decrease in the threshold for experience-driven plasticity. Hippocampus-dependent learning and memory emerge late in altricial mammals [ 14 , 15 , 16 , 17 ], appearing around weaning in rats and slowly maturing thereafter [ 14 , 15 ]. In contrast, spatially localized firing is observed 1 week earlier (with reduced spatial tuning and stability) [ 18 , 19 , 20 , 21 ]. By examining the development of hippocampal reactivation, replay, and theta sequences, we show that the coordinated maturation of offline consolidation and online sequence generation parallels the late emergence of hippocampal memory in the rat.

Hippocampal gamma rhythms during Y‐maze navigation in the juvenile rat

“…While stable place cells are present as early as postnatal day (P) 16 in rats (Langston et al, ; Wills, Cacucci, Burgess, & O'Keefe, ), they appear insufficient to support navigation according to spatial context. Supporting this notion, sequential firing of place cells along trajectories associated with online navigation, and their temporally compressed replay during immobility and sleep, does not emerge until after the third postnatal week (Farooq & Dragoi, ; Muessig, Lasek, Varsavsky, Cacucci, & Wills, ). Given the role of gamma oscillations in coordinating place cell ensemble activity in adults, in addition to other aspects of spatial information processing, it is possible that changes in gamma oscillations during the third postnatal week are necessary to enable spatial navigation ability.…”

Cognitive swarming in complex environments with attractor dynamics and oscillatory computing

“…Additionally, spatial activity in the rodent hippocampus is strongly modulated by continuous theta oscillations (5-12 Hz) during locomotion (Vanderwolf, 1969;Buzsáki, 2005). The resulting 'phase precession,' a monotonic advance in timing from late to early within each theta cycle, may enhance the precision and temporal organization of spatial codes (O'Keefe and Recce, 1993;Jensen and Lisman, 2000;Foster and Wilson, 2007;Drieu et al, 2018) in ways that support decisionmaking and/or deliberative planning during subsequent sleep or quiescent states (Buzsáki, 1989;Johnson and Redish, 2007;Buzsáki and Moser, 2013;Wikenheiser and Redish, 2015;Papale et al, 2016;Muessig et al, 2019). Recently, in contrast to phase precession, we discovered a novel class of spatial phase-coding neurons in open field environments termed 'phaser cells' that were located predominantly in the rat lateral septum and characterized by a strong coupling of theta-phase timing to firing rates (Monaco et al, 2019a).…”

Memory: Sequences Take Time

“…But the question of why we struggle to remember even the most salient events from our early lives remains poorly understood. A new study by Muessig et al [2], reported in this issue of Current Biology, delivers fresh insight into how the hippocampal processes thought to underlie memory evolve during development, providing an answer to this long-standing question.…”

“…In the new study, Muessig et al [2] set out to explain the temporal discrepancy that exists between the place coding present even in the very young mammalian hippocampus and the delayed emergence of hippocampal-dependent memory. They took a systematic approach, detailing the key processes involved -place coding, theta sequences and replayand characterizing their progression through early development to their final, stable endpoint in young adulthood.…”

“…While this may be purely coincidental, it is intriguing that children learn to construct complete sentences in an almost identical fashion, initially focusing on a key word or two, before gradually learning to piece together longer and longer strings of words in the correct order. Finally, Muessig et al [2] characterized theta sequences which they showed developed in a similar fashion to replay events, initially focusing only on the animal's current location at P17 before spreading further and further to positions backwards and forwards in time, with age.…”