In a first, brain memory shown to have two distinct past and future paths for behavior

Amazing stuff!

"For the first time, a study in rats teases apart the role of the hippocampus in two functions of memory – one that remembers associations between time, place and what one did, and another that allows one to predict or plan future actions based on past experiences. ...
“We uncovered that two different neural codes support these very important aspects of memory and cognition, and can be dissociated, as we did experimentally,” ..."

From the editor's note and abstract:

"Editor’s summary

Synchronous hippocampal neuronal ensemble activity supports episodic memory. This observation has led to the view that the main function of the hippocampus is to encode associations among different elements of an experience. However, an alternative hypothesis is that the hippocampus generates predictive representations of the world that can guide flexible behaviors. Liu et al. disrupted input from the entorhinal cortex to hippocampal area CA1 ... thus destroying the sequence dynamics of place cells while keeping their coincidental firing intact. Sequence replay was disrupted but assembly reactivations were preserved. Different CA1 codes thus serve corresponding memory operations, with the place code supporting associative memory tasks and the sequence code supporting tasks that require learning about predictive transitions in space. ...

Structured Abstract

...

RATIONALE

We hypothesize that two modes of hippocampal activity support learning of world states and state transitions, respectively. On one hand, the synchronous coactivity of groups of hippocampal neurons—cell assemblies—may encode features of individual states, forming an associative code. On the other hand, the ordered activation of these cell assemblies into behaviorally relevant sequences may encode the relational structure between states, forming a predictive code. Previous research has not been able to dissociate these two dynamic codes or provide evidence of their specific functions. We leveraged an optogenetic approach to dissociate these two coding schemes, with the goal of disrupting the predictive code (hippocampal sequences) while preserving the associative code (rate coding and coactivity dynamics) in behaving rats. This dissociation allowed us to examine the different memory functions of these two codes.

RESULTS

We optogenetically perturbed the fine temporal coordination of hippocampal place cell firing as rats navigated specific spatial trajectories in a novel maze. This manipulation disrupted properties of the predictive code (such as temporally compressed place cell sequences and anticipatory place field shifts), but global network dynamics and single-cell spatial tuning and rate coding properties were preserved.

During sleep after the novel experience, we observed that task-related cell assemblies encoding discrete maze locations were reactivated in sharp wave–ripples (SWRs), unaffected by the manipulation. However, their sequential structure did not reproduce the order in which they were active in the task, resulting in impaired sequential replay for the perturbed trajectories. This result shows a dissociation between assembly reactivation and sequence replay, two phenomena previously assumed to reflect the same underlying process. The same manipulation did not disrupt replay of familiar trajectories, suggesting that the precise temporal coordination of place cell firing during learning mediates initial plasticity required for subsequent replay. Computational simulations suggest that distinct Hebbian plasticity mechanisms mediate assembly reactivation and sequence replay.

We tested the functional role of the predictive code by deploying our optogenetic manipulation in two different hippocampal-dependent memory tasks. Context-reward associative learning in a conditioned place preference task was unaffected and thus does not require a predictive map or memory replay. On the other hand, flexible memory–guided navigation in a foraging task was perturbed by the manipulation and thus depends on hippocampal predictive coding.

CONCLUSION

Our results provide a mechanistic and functional dissociation between coactivity and sequence codes in the hippocampus. Hippocampal cells with similar responses to behavioral variables fire together, forming functional assemblies during learning, which are reactivated in SWRs during subsequent sleep. These cell assemblies encode discrete states in the environment, an associative code that is sufficient for some types of episodic memories. As these cell assemblies are activated in a specific order during behavior, they form temporally compressed hippocampal sequences and promote Hebbian plasticity. This process enables the replay of behaviorally relevant sequences during SWRs. Hippocampal sequences thus encode transitional structures of world states, generating a predictive model on top of the associative code of individual assemblies. This new framework contributes to our understanding of how memory associations develop into predictive representations of the world and helps reconcile previously disparate views on hippocampal function."

In a first, memory shown to have two distinct past and future paths

Role of hippocampus in two functions of memory revealed

Associative and predictive hippocampal codes support memory-guided behaviors (no public access)

Associative and predictive codes in the hippocampus.