A neural signature of pattern separation in the monkey hippocampus

Sakon, John J.; Suzuki, Wendy

doi:10.1073/pnas.1900804116

Cited by 34 publications

(54 citation statements)

References 45 publications

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“…1D, E). Shuffling analysis (see Methods) confirmed that network events cannot arise by chance (Fig 1E, grey bars correspond to shuffled data, ANOVA F (3,25) =30.12, p=4*10 -14 , Bonferroni post-test resting vs. shuffled p=2.2*10 -10 indicated with asterisk, running vs. shuffled p=1). Simultaneous imaging of MPP and GC activity showed that network events were strongly correlated with MPP activity increases (Fig.…”

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confidence: 59%

“…This capability requires the animal to generate dissimilar neuronal representations from overlapping input states that represent similar but not identical environments 1 . Such an operation, termed pattern separation, has been ascribed to the hippocampal dentate gyrus in species ranging from rodents to humans [2][3][4] . In the dentate gyrus, polysensory inputs are mapped onto a large number of granule cells which exhibit extremely sparse firing patterns, resulting in a high probability of non-overlapping output patterns [5][6][7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

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Dentate gyrus population activity during immobility supports formation of precise memories

Pofahl

Nikbakht

et al. 2020

Preprint

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All vertebrates are capable of generating dissimilar patterns of neuronal activity from similar sensory-driven input patterns, a phenomenon called pattern separation. It is unclear, however, how these separated patterns are transformed into lasting memories that retain the initial discrimination. Using dual-color in-vivo two-photon Ca 2+ imaging, we show that the dentate gyrus, a region implicated in pattern separation, generates in immobile mice sparse, synchronized activity patterns driven by entorhinal cortex activity. These population events are structured and modified by changes in the environment; they incorporate place-and speed cells and are similar to population patterns evoked during self-motion. Inhibiting only granule cells in immobile mice impairs formation of pattern-separated memories. These patterns, thus, support the creation of precise memories by replaying the population codes of the current environment on a short time scale. Results Sparse, structured dentate network events in immobile animalsWe imaged the activity of >300 granule cells (GCs) using a Thy1-GCaMP6s mouse line (GP4.12Dkim/J,15 ). In addition, we monitored the activity of the major input system into the dentate gyrus, the medial perforant path (MPP). To this end, we expressed the red-shifted Ca 2+ indicator jRGECO1a 16 in the medial entorhinal cortex using viral gene transfer (see Methods section, Fig. 1A, B, Supplementary Fig. 1A). To allow efficient excitation of both genetically encoded Ca 2+ indicators, we established excitation with two pulsed laser sources at 940 and 1070 nm (see Supplementary Fig. 1B). The mice were placed under a two photon microscope and ran on a linear track (see Supplementary Fig. 1C, Supplementary Movie 1).As previously described, the firing of GCs was generally sparse 7-9,17 , both when animals were immobile and running on a textured belt without additional cues (mean event frequency 1.38±0.19 events/min and 0.97±0.2 events/min, respectively, n=9 mice, Fig. 1B, Supplementary Fig. 2C-F). Despite the sparse activity of granule cells, we observed synchronized activity patterns. To rigorously define such events, we used an algorithm that detects synchronized network events within a 200 ms time window (see Methods). Such synchronous network events could readily be observed in the dentate gyrus ( Fig. 1C, D, network events depicted in different colors, see corresponding Supplementary Movie 2).Network events were sparse, incorporating only 5.7±0.09 % of the active GC population.Notably, network events occurred mainly during immobility and were much less prevalent during running (Fig. 1D, E). Shuffling analysis (see Methods) confirmed that network events cannot arise by chance (Fig 1E, grey bars correspond to shuffled data, ANOVA F (3,25) =30.12, p=4*10 -14 , Bonferroni post-test resting vs. shuffled p=2.2*10 -10 indicated with asterisk, running vs. shuffled p=1). Simultaneous imaging of MPP and GC activity showed that network events were strongly correlated with MPP activity increases (Fig. 1F). Moreover, ...

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confidence: 59%

Section: Introductionmentioning

confidence: 99%

Dentate gyrus population activity during immobility supports formation of precise memories

Pofahl

Nikbakht

et al. 2020

Preprint

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“…Finally, both gaze reinstatement (35; see also, ref. 60) and other retrieval-related EM effects (61)(62)(63) have been linked to activity in the hippocampus. Considered together with the present results, these findings suggest that the outcome of behavioral pattern completion (i.e., lure false alarms) may be attributed, at least in part, to the hippocampally mediated reactivation of relational information, reflected, and likely supported by gaze reinstatement.…”

Section: Discussionmentioning

confidence: 99%

Eye movements support behavioral pattern completion

Wynn

Ryan

Buchsbaum

2020

Proc. Natl. Acad. Sci. U.S.A.

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The ability to recall a detailed event from a simple reminder is supported by pattern completion, a cognitive operation performed by the hippocampus wherein existing mnemonic representations are retrieved from incomplete input. In behavioral studies, pattern completion is often inferred through the false endorsement of lure (i.e., similar) items as old. However, evidence that such a response is due to the specific retrieval of a similar, previously encoded item is severely lacking. We used eye movement (EM) monitoring during a partial-cue recognition memory task to index reinstatement of lure images behaviorally via the recapitulation of encoding-related EMs or gaze reinstatement. Participants reinstated encoding-related EMs following degraded retrieval cues and this reinstatement was negatively correlated with accuracy for lure images, suggesting that retrieval of existing representations (i.e., pattern completion) underlies lure false alarms. Our findings provide evidence linking gaze reinstatement and pattern completion and advance a functional role for EMs in memory retrieval.

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“…The dentate gyrus (DG)-CA3 circuit in dHC is thought to play a critical role in resolving overlapping contextual information to distinguish between certain and ambiguous threats (Besnard and Sahay, 2016;McHugh et al, 2007). At the neural level, this may be accomplished by pattern separation, a mechanism by which similar inputs are made divergent at the level of output (Berron et al, 2016;Besnard and Sahay, 2016;Deng et al, 2013;Lee et al, 2015;Leutgeb et al, 2007;Madar et al, 2019aMadar et al, , 2019bMcAvoy et al, 2016;Miller and Sahay, 2019;Neunuebel and Knierim, 2014;Sakon and Suzuki, 2019). Intriguingly, CA1 appears to be less sensitive to contextual discrimination and pattern separation, raising the question of how DG-CA3 computations resolving overlapping contextual information are propagated to extrahippocampal circuits without being modified or undone in CA1 (Knierim and Neunuebel, 2016;Leutgeb et al, 2004;Vazdarjanova and Guzowski, 2004;Yassa and Stark, 2011).…”

Section: Introductionmentioning

confidence: 99%

Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

2020

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Considerable work emphasizes a role for hippocampal circuits in governing contextual fear discrimination. However, the intra-and extrahippocampal pathways that route contextual information to cortical and subcortical circuits to guide adaptive behavioral responses are poorly understood. Using terminal-specific optogenetic silencing in a contextual fear discrimination learning paradigm, we identify opposing roles for dorsal CA3-CA1 (dCA3-dCA1) projections and dorsal CA3-dorsolateral septum (dCA3-DLS) projections in calibrating fear responses to certain and ambiguous contextual threats, respectively. Ventral CA3-DLS (vCA3-DLS) projections suppress fear responses in both certain and ambiguous contexts, whereas ventral CA3-CA1 (vCA3-vCA1) projections promote fear responses in both these contexts. Lastly, using retrograde monosynaptic tracing, ex vivo electrophysiological recordings, and optogenetics, we identify a sparse population of DLS parvalbumin (PV) neurons as putative relays of dCA3-DLS projections to diverse subcortical circuits. Taken together, these studies illuminate how distinct dCA3 and vCA3 outputs calibrate contextual fear discrimination.

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A neural signature of pattern separation in the monkey hippocampus

Cited by 34 publications

References 45 publications

Dentate gyrus population activity during immobility supports formation of precise memories

Dentate gyrus population activity during immobility supports formation of precise memories

Eye movements support behavioral pattern completion

Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

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