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The brain codes continuous spatial, temporal and sensory changes in daily experience. Recent studies suggest that the brain also tracks experience as segmented subdivisions (events), but the neural basis for encoding events remains unclear. Here, we designed a maze for mice, composed of four materially indistinguishable lap events, and identify hippocampal CA1 neurons whose activity are modulated not only by spatial location but also lap number. These ‘event-specific rate remapping’ (ESR) cells remain lap-specific even when the maze length is unpredictably altered within trials, which suggests that ESR cells treat lap events as fundamental units. The activity pattern of ESR cells is reused to represent lap events when the maze geometry is altered from square to circle, which suggests that it helps transfer knowledge between experiences. ESR activity is separately manipulable from spatial activity, and may therefore constitute an independent hippocampal code: an ‘event code’ dedicated to organizing experience by events as discrete and transferable units.Hippocampal neurons track events as abstract units of episodic experience. These event representations can be transferred between different experiences and are separately manipulable from hippocampal representations of continuous changes in space.

A Correction to this paper has been published: https://doi.org/10.1038/s41593-020-00790-5.

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward – even prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex. Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic receptor signaling, while also facilitating firing in BLA GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward – even prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex. Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic receptor signaling, while also facilitating firing in BLA GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

A general wisdom is that experiences need to be tagged during learning for further consolidation. However, brain mechanisms that select experiences for lasting memory are not known. Combining large-scale neural recordings with a novel application of dimensionality reduction techniques, we observed that successive traversals in the maze were tracked by continuously drifting populations of neurons, providing neuronal signatures of both places visited and events encountered (trial number). When the brain state changed during reward consumption, sharp wave ripples (SPW-Rs) occurred on some trials and their unique spike content most often decoded the trial in which they occurred. In turn, during post-experience sleep, SPW-Rs continued to replay those trials that were reactivated most frequently during awake SPW-Rs. These findings suggest that replay content of awake SPW-Rs provides a tagging mechanism to select aspects of experience that are preserved and consolidated for future use.

Neurons in the hippocampus are correlated with different variables, including space, time, sensory cues, rewards, and actions, where the extent of tuning depends on ongoing task demands. However, it remains uncertain whether such diverse tuning corresponds to distinct functions within the hippocampal network or if a more generic computation can account for these observations. To disentangle the contribution of externally driven cues versus internal computation, we developed a task in mice where space, auditory tones, rewards, and context were juxtaposed with changing relevance. High-density electrophysiological recordings revealed that neurons were tuned to each of these modalities. By comparing movement paths and action sequences, we observed that external variables had limited direct influence on hippocampal firing. Instead, spiking was influenced by online action plans modulated by goal uncertainty. Our results suggest that internally generated cell assembly sequences are selected and updated by action plans toward deliberate goals. The apparent tuning of hippocampal neuronal spiking to different sensory modalities might emerge due to alignment to the afforded action progression within a task rather than representation of external cues.

In real life, success is often contingent upon multiple critical steps that are distant in time from each other and from the final reward. These critical steps are challenging to identify with traditional reinforcement learning (RL) methods that rely on the Bellman equation for credit assignment. Here, we present a new RL algorithm that uses offline contrastive learning to hone in on these critical steps. This algorithm, which we call Contrastive Retrospection (ConSpec), can be added to any existing RL algorithm. ConSpec learns a set of prototypes for the critical steps in a task by a novel contrastive loss and delivers an intrinsic reward when the current state matches one of the prototypes. The prototypes in ConSpec provide two key benefits for credit assignment: (i) They enable rapid identification of all the critical steps. (ii) They do so in a readily interpretable manner, enabling out-of-distribution generalization when sensory features are altered. Distinct from other contemporary RL approaches to credit assignment, ConSpec takes advantage of the fact that it is easier to retrospectively identify the small set of steps that success is contingent upon (and ignoring other states) than it is to prospectively predict reward at every taken step. ConSpec greatly improves learning in a diverse set of RL tasks. The code is available at the link: https://github.com/sunchipsster1/ConSpec

A prevailing view is that the brain represents episodic experience as the continuous moment to moment changes in the experience. Whether the brain also represents the same experience as a sequence of discretely segmented events, is unknown. Here, we report a hippocampal CA1 'chunking code', tracking an episode as its discrete event subdivisions ('chunks') and the sequential relationships between them. The chunking code is unaffected by unpredicted variations within the events, reflecting the code's flexible nature by being organized around events as abstract units. The chunking code changes accordingly when relationships between events are disrupted or modified. The discrete chunking code and continuous spatial code are represented in the same cells, but in an orthogonal manner, and can be independently perturbed. Optogenetic inactivation of MEC inputs to CA1 disrupts the chunking but not spatial code. The chunking code may be fundamental for representing an episode, alongside codes tracking continuous changes.

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward – even in prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex (PFC). Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic-receptor-signaling, while also facilitating firing in GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

Neurons in the retrohippocampal cortices play crucial roles in spatial memory. Many retrohippocampal neurons have firing fields that are selectively active at specific locations, with memory for rewarded locations associated with reorganisation of these firing fields. Whether this is the sole strategy for representing spatial memories is unclear. Here, we demonstrate that during a spatial memory task retrohippocampal neurons encode location through ramping activity that extends within segments of a linear track approaching and following a reward, with the rewarded location represented by offsets or switches in the slope of the ramping activity. These ramping representations could be maintained independently of trial outcome and cues that mark the reward location, indicating that they result from recall of the track structure. During recordings in an open arena, neurons that generated ramping activity during the spatial memory task were more numerous than grid or border cells, with a majority showing spatial firing that did not meet criteria for classification as grid or border representations. Encoding of rewarded locations through offsets and switches in the slope of ramping activity also emerged in recurrent neural networks trained to solve a similar location memory task. Impaired performance of these networks following disruption of outputs from ramping neurons is consistent with this coding strategy supporting navigation to recalled locations of behavioural significance. We hypothesise that retrohippocampal ramping activity mediates readout of learned models for goal-directed navigation. Competing Interest Statement The authors have declared no competing interest. Footnotes * Modified methods for generating shuffled control data (Figure 1) and for model fitting (Figure 2). Additional simulation experiments to examine consequences of perturbation of the model network (Figure 7). Numerous minor changes.