DG-CA3 circuitry mediates hippocampal representations of latent information

Abstract

words) 26Survival in complex environments necessitates a flexible navigation system that incorporates 27 memory of recent behavior and associations. Yet, how the hippocampal spatial circuit 28 represents latent information independent of sensory inputs and future goals has not been 29 determined. To address this, we imaged the activity of large ensembles in subregion CA1 via 30 wide-field fluorescent microscopy during a novel behavioral paradigm. Our results demonstrated 31 that latent information is represented through reliable firing rate changes during unconstrained 32 navigation. We then hypothesized that the representation of latent information in CA1 is 33 mediated by pattern separation/completion processes instantiated upstream within the dentate 34 gyrus (DG) and CA3 subregions. Indeed, CA3 ensemble recordings revealed an analogous 35 code for latent information. Moreover, selective chemogenetic inactivation of DG-CA3 circuitry 36 completely and reversibly abolished the CA1 representation of latent information. These results 37 reveal a causal and specific role of DG-CA3 circuitry in the maintenance of latent information 38 within the hippocampus. 39 40 41 42 43 44 45

Abrupt remapping in human CA3/dentate gyrus signals resolution of memory interference

“…The fact that CA23DG exaggerated the representational distance between competing scenes (remapping) while simultaneously reflecting learned associations (scene-object similarity) is consistent with the idea that CA3 balances both pattern separation and pattern completion mechanisms 4,17,36,37 . The fact that remapped activity patterns contained information about learned associations is also consistent with the argument that hippocampal remapping does not simply reflect changes in the external environment—which did not change over the course of the experiment—but instead fundamentally reflects changes in internal models of the environment 14,15 .…”

“…These findings were motivated by—and complement—existing evidence of remapping in the rodent hippocampus. Yet, our findings also go beyond existing rodent or human studies by establishing a direct link between remapping and changes in internal memory states 14,15 . Additionally, our conclusion that overlap among CA3/dentate gyrus representations actively triggers a repulsion of memory representations has important implications for theoretical accounts of how the hippocampus resolves memory interference 5,8,36,39 and will hopefully inspire targeted new analyses that test for similar mechanisms in rodent models.…”

“…However, abrupt remapping can also occur as a function of experience with a new environment 10,12 . Evidence of experience-dependent remapping 6,13 suggests an important point: that remapping fundamentally reflects changes in internal representations, as opposed to changes in environmental states 14,15 . An emphasis on internal representations lends itself well to human episodic memory in that it suggests that hippocampal remapping should occur as memories change .…”

“…Evidence of place cell remapping in rodents also motivates specific predictions regarding the relative contributions of hippocampal subfields, with a major distinction being between CA3/dentate gyrus and CA1 8,16,17 . In general, CA3 and dentate gyrus are thought to be more important than CA1 for discriminating between similar stimuli 15,17–20 and remapping has been shown to occur more abruptly in CA3 than in CA1 10,12,21 . Human fMRI studies also support this general distinction, with several studies specifically implicating CA3 and dentate gyrus in discriminating similar memories 22–27 .…”

Representational content determines the long-term dynamics of the CA1 spatial code

“…Hippocampal subregion CA1 represents a mixture of external and internal cuesincluding the shape of the environment 1 , visual landmarks 2,3 , objects 4 , task-relevant information 5 , and past experience [6][7][8][9] through changes to the spatial tuning properties of its principal cells 10 . This code is hypothesized to support spatial and episodic memory by later reinstating its content.…”