Hippocampal-prefrontal input supports spatial encoding in working memory

Spellman, Rigotti, Ahmari, Fusi, Gogos, Gordon · Nature · 2015 · neuroscience · 10.1038/nature14445 · record Spellman2015-hippocampal-prefrontal-input-supports-spatia
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Where this record's text came from. faceted 2026-08 by reading the locally held text (xml); every evidence string verified as an exact substring of that text before merging. Only one claim_relation is recorded because the paper cites prior work by superscript number rather than by name; the discussion does relate itself to unnamed refs 36-43 (e.g. offering an alternative explanation for a previous vHPC-silencing result and 'extending previous work' on contextual learning), but no name is given in the text so those were left out under the named-prior-work rule. The paper reports internal replication of its main behavioural result ('replicated across both behavioral paradigms used in this study'); replication status is nonetheless recorded as untested because no independent replication is claimed. Method is tagged electrophysiology, but the study equally combines projection-specific optogenetics with a T-maze behavioural task, which the single method facet cannot express. 2026-08-13 and 2026-08-15 schema-0.3 passes: every quote verified as an exact substring of the staged text and anchored at merge time; concept terms verified present; every edge endpoint an existing node.
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Other fields define these differently the same word, defined another way in another discipline
cross-validation 3 fields · maintenance 2 fields

Tags on this paper

Every tag the record carries, each linking to every other paper in the corpus that carries it. A tag appears here whether or not its words occur in the article — the spans below are only the ones a sentence in this paper licenses. Of the 14 concept tags on this paper, none is grounded in a quoted sentence. All carry the tagger's gloss of what the term means in this paper, which is not something the article can license.
spatial working memory encoding retrieval maintenance vHPC mPFC gamma theta pairwise phase consistency lag analysis archaerhodopsin delayed non-match-to-place retrospective location coding nucleus reuniens Gamma-frequency synchronization between vHPC and mPFC carries the spatial cue across the direct projection, so that entrainment of mPFC spikes to vHPC gamma is what enables successful encoding. vHPC gamma oscillations entrain vHPC output in phase, which then influences mPFC spike timing at monosynaptic delays, making spike entrainment the physical signature of the signal being propagated. The vHPC input acts excitatorily on mPFC units, driving the location-selective elevation of firing rate that constitutes the cue representation. medial prefrontal cortex phase-locking optogenetic terminal inhibition T-maze prelimbic decoding goal selectivity projection-specific sample phase delay phase preferred goal opsin-negative control intra-trial delay firing rate gamma phase-locking 4-goal T-maze sample goal identity ANOVA repeated-measures ANOVA repeated measures group-by-condition tests paired t-test paired t-tests or (where stated) signed rank tests Bonferroni correction for multiple comparisons significance threshold (alpha) Rayleigh test of circular uniformity Rayleigh's test pairwise phase consistency (spike-field phase-locking measure) linear classifier / population decoding maximum margin linear classifier cross-validation cross-validated by training on data from half of the trials and testing resampling with replacement (bootstrap) randomly resampled with replacement statistical power analysis / effect size post-hoc power analysis maximum margin linear classifier, cross-validated electrophysiology

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second readingalternativesan independent re-reading of a facet, recorded whether or not it agrees
relation to other workclaim_relationshow this paper stands to another: agrees, contradicts, extends, qualifies
claim typeclaim_typethe shape of the claim: existence, mechanism, method, critique, prediction, null
concept edgeconcept_edgesan asserted relation between two concepts, with the sentence asserting it
content tagcontent_tagsa finding, definition, quantity, statistic or variable named in the paper
contributioncontributionwhat the paper claims to add
controlcontrolsan experiment run to eliminate a rival explanation
limitationlimitationswhat the paper says its evidence cannot support
mechanismmechanismshow the reported effect is said to come about
methodmethodhow the paper produced its evidence
object of studyobject_of_studywhat the paper is about — the thing it investigates
phenomenonphenomenonthe effect or regularity under study
research questionresearch_questionthe question the paper sets itself
sensesensesa distinct use of a term, quoted where the paper fixes it
transfertransfersa method or concept carried in from another field

The paper

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alternatives 2 · claim_relations 5 · claim_type 1 · concept_edges 3 · content_tags 69 · contribution 1 · controls 2 · limitations 11 · mechanisms 9 · method 1 · object_of_study 1 · phenomenon 1 · research_question 1 · senses 4 · transfers 2

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facettagfieldconf.whose words
object_of_studythe direct ventral hippocampus to medial prefrontal cortex projection during spatial working memory
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object_of_studythe paper's words
research_questionwhich phase of spatial working memory requires this pathway, what it carries, and by what anatomical route
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research_questionthe paper's words
contributionshows the pathway is needed for encoding but not maintenance or retrieval, both behaviourally and in the prefrontal representation, with gamma synchrony as the carrier
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contributionthe paper's words
claim_typemechanism
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claim_typethe paper's words
phenomenonspatial working memory
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phenomenonthe paper's words
methodelectrophysiology
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methodthe paper's words
mechanismsmechanisms
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mechanisms[0]the tagger's words
mechanismsmechanisms
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mechanisms[1]the tagger's words
mechanismsmechanisms
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mechanisms[2]the tagger's words
mechanismsvHPC input drives a selective firing-rate elevation in each unit's preferred goal, without changing baseline rates
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mechanisms[3]1.0the tagger's words
mechanismsthe same goal selectivity persists during choice runs and no longer needs vHPC input, so physiology mirrors the behavioural dissociation
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mechanisms[4]1.0the tagger's words
mechanismsvHPC gamma leads mPFC spiking at lags consistent with monosynaptic transmission, and terminal inhibition reduces that phase-locking
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mechanisms[5]1.0the tagger's words
mechanismsthe directionality is specific to gamma: in theta the mPFC leads, and theta synchrony survives terminal inhibition
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mechanisms[6]1.0the tagger's words
mechanismsterminal illumination suppresses transmission without silencing the source cells, which is what makes the manipulation projection-specific
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mechanisms[7]1.0the tagger's words
mechanismsa four-goal maze prevents the animal from forming a spatially directed plan until the choice phase, which is what separates encoding from retrieval
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mechanisms[8]1.0the tagger's words
limitationsThe authors cannot definitively exclude an effect of terminal inhibition during the choice (retrieval) phase; the null result there was underpowered.
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what this limits: the encoding claim as against the choice phase: ALTHOUGH WE CANNOT CONCLUSIVELY RULE OUT AN EFFECT OF TERMINAL INHIBITION DURING CHOICE, THESE EXPERIMENTS INDICATE THAT INPUT FROM THE vHPC TO THE mPFC IS CRITICAL FOR ENCODING
limitations[0]the tagger's words
limitationsRetrospective location coding might exist in mPFC in a form their decoding analysis could not detect (e.g. synaptic weights or very brief reactivation).
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what this limits: the absence of retrospective coding, which is scoped to the ANALYSIS: IT IS NOT DETECTABLE USING THE ANALYTIC TECHNIQUES PRESENTED HERE, SUCH AS in synaptic weights or in reactivation too brief for the bins
limitations[1]the tagger's words
limitationsThe pseudo-population decoding approach assumes comparable spike statistics across animals and sessions and discards correlated variability.
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what this limits: every population-decoding result: THIS APPROACH ASSUMES EQUIVALENT SPIKE STATISTICS ACROSS ANIMALS AND RECORDING SESSIONS, AND IGNORES POTENTIAL CONTRIBUTIONS TO POPULATION CODING FROM CORRELATED SPIKE VARIABILITY
limitations[2]the tagger's words
limitationsThe gamma phase-locking effect is small: under 10% of mPFC units were significantly phase-locked even at the best lag.
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what this limits: the gamma phase-locking claim, with its size: AT THE LAG WITH THE GREATEST PHASE-LOCKING, FEWER THAN 10% OF mPFC UNITS WERE SIGNIFICANTLY PHASE-LOCKED TO vHPC GAMMA
limitations[3]the tagger's words
limitationsthe choice-phase null is not conclusive; an n of 37 per group would have been needed to detect the observed effect size
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what this limits: the choice-phase null, with what it would have taken to see the effect: A SLIGHT TREND TOWARD IMPAIRMENT DID NOT REACH SIGNIFICANCE, AND POST-HOC POWER ANALYSIS REVEALED THAT AN n OF 37 PER GROUP would have been required
limitations[4]1.0the tagger's words
limitationsthe authors state plainly that they cannot conclusively rule out an effect during choice
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duplicate of: limitations[0] · what this limits: the same scope as limitations[0] - an effect during choice is not conclusively excluded
limitations[5]1.0the tagger's words
limitationsthe absence of retrospective coding is scoped to the analysis: it could be held in synaptic weights or in reactivation too brief to decode from binned histograms
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what this limits: the same scope as limitations[1] - the null on retrospective coding is a null of the method
limitations[6]1.0the tagger's words
limitationsthe gamma effect is subtle - fewer than 10% of mPFC units were significantly phase-locked at the best lag
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duplicate of: limitations[3] · what this limits: the same scope as limitations[3] - under 10% of units, at the best lag
limitations[7]1.0the tagger's words
limitationsthe promoter was changed between the two behavioural experiments, so they are not methodologically identical
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what this limits: any comparison BETWEEN the two behavioural experiments: THE hSYNAPSIN PROMOTER WAS CHOSEN FOR THE 4-GOAL EXPERIMENT TO ACCOUNT FOR POSSIBLE LONG-RANGE GABAERGIC vHPC-mPFC PROJECTIONS AND TO AVOID POTENTIAL TOXICITY EFFECTS - so they differ in more than the goal count
limitations[8]0.9the tagger's words
limitationsmale mice only
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what this limits: any sex-general reading: MALE C57BL/6 MICE (JACKSON LABS) WERE USED FOR ALL EXPERIMENTS
limitations[9]0.85the tagger's words
limitationsthe theta result ran counter to the authors' initial hypotheses and is reported as such
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what this limits: the theta result specifically: THE FINDING THAT mPFC THETA ACTIVITY LEADS vHPC THETA, AND THAT THETA SYNCHRONY BETWEEN THE TWO STRUCTURES DID NOT APPEAR TO DEPEND UPON vHPC-mPFC AFFERENTS, RAN COUNTER TO OUR INITIAL HYPOTHESES
limitations[10]1.0the tagger's words
transfersdelay-period persistent firing as the expected mechanism, imported and then not found in the rodent homologue
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transfers[0]0.95the tagger's words
transfersa maximum margin linear classifier with cross-validation, used to read location from distributed population rates
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transfers[1]1.0the tagger's words
controlsa CamKIIα-mCherry virus carrying no opsin, run in the acute stimulation/silencing and 2-goal t-maze experiments
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eliminates: the light delivery and the viral infection themselves as the cause of the behavioural effect - the exclusion is carried by the term OPSIN-NEGATIVE CONTROL rather than spelled out · outcome (stated by the tagger, no quotation): held
controls[0]0.8the tagger's words
controlsthe researcher who trained and ran the mice was blinded to viral group by a second lab member, who did the assignment
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eliminates: the experimenter's knowledge of which animals carried the opsin influencing training or scoring · outcome (stated by the tagger, no quotation): held
controls[1]0.8the tagger's words
sensesencoding, maintenance and retrieval are defined by TRIAL PHASE and made separable by a maze redesign - the distinction is built into the apparatus, not read off the behaviour
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senses[0]1.0the tagger's words
sensesprojection-specific means the terminals are silenced where they arrive, not the cells that send them - validated by showing vHPC firing is untouched by mPFC illumination
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senses[1]1.0the tagger's words
sensesno evidence of retrospective coding is scoped explicitly to the analytic technique, naming two forms it could take and still be missed
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senses[2]1.0the tagger's words
sensesfunctionally analogous but anatomically distinct - the stated relation between primate dorsolateral PFC and rodent prelimbic cortex, which licenses comparing them cautiously
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senses[3]1.0the tagger's words
alternativesmethod: projection-specific optogenetic terminal inhibition with archaerhodopsin, timed to single trial phases, combined with prefrontal single-unit recording and population decoding
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a second reading DIFFERING from the recorded value. Recorded: electrophysiology — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides.
alternatives.methodthe tagger's words
alternativesphenomenon: phase-specific long-range routing of spatial information during working memory
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a second reading DIFFERING from the recorded value. Recorded: spatial working memory — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides.
alternatives.phenomenonthe tagger's words
claim_relationsbuilds-on → Wang et al., 2006 (adaptive intra-trial delay procedure for the T-maze task)
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claim_relations[0]the tagger's words
claim_relationsqualifies → prior reports of retrospective and prospective location coding in rodent mPFC during delays
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claim_relations[1]1.0the tagger's words
claim_relationsreinterprets → the earlier finding that vHPC silencing reduces dHPC-mPFC theta synchrony, proposing it was an indirect effect on dHPC
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claim_relations[2]1.0the tagger's words
claim_relationsextends → work implicating vHPC and mPFC in contextual learning, by moving it to a seconds timescale
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claim_relations[3]0.9the tagger's words
claim_relationscontradicts → persistent prefrontal firing as the mechanism maintaining the cue between encoding and retrieval
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claim_relations[4]0.95the tagger's words
concept_edgesencoding —contrasted-with→ retrieval
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differs in: THE AXIS IS WHICH PHASE OF THE MEMORY THE PATHWAY IS NEEDED FOR, AND THREE PHASES ARE NAMED. 'Quotation withheld.' The same anatomy is necessary at one moment of a trial and dispensable at the others - so a lesion or inactivation that spans the whole trial cannot produce this result, and studies that do span it will report the pathway as generally required. · strength of the relation: 1
also in: encoding · retrieval
concept_edges[1]1.0the tagger's words
concept_edgesgamma —contrasted-with→ theta
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differs in: THE AXIS IS FREQUENCY BAND, AND THE DIRECTION OF FLOW REVERSES WITH IT. 'Quotation withheld.' The same two structures lead each other in opposite directions depending on the band - so a connectivity claim without the band is not merely imprecise, it is ambiguous between two opposite claims. · strength of the relation: 1 · note: opposite directionality between the same two structures, and only gamma depends on the direct pathway
also in: gamma · theta
concept_edges[2]1.0the tagger's words
concept_edgesgamma —operationalised-as→ pairwise phase consistency
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strength of the relation: 0.95 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but long-range gamma synchrony was quantified with pairwise phase consistency; operationalised-as is loose.
concept_edges[4]1.0the tagger's words
content_tagsANOVA
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also in: ANOVA
content_tags.statistics[0]the tagger's words
content_tagsrepeated-measures ANOVA
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content_tags.statistics[1]the tagger's words
content_tagspaired t-test
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also in: paired t-test
content_tags.statistics[2]the tagger's words
content_tagsBonferroni correction for multiple comparisons
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content_tags.statistics[3]the tagger's words
content_tagssignificance threshold (alpha)
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content_tags.statistics[4]the tagger's words
content_tagsRayleigh test of circular uniformity
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content_tags.statistics[5]the tagger's words
content_tagspairwise phase consistency (spike-field phase-locking measure)
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content_tags.statistics[6]the tagger's words
content_tagslinear classifier / population decoding
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content_tags.statistics[7]the tagger's words
content_tagscross-validation
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content_tags.statistics[8]the tagger's words
content_tagsresampling with replacement (bootstrap)
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content_tags.statistics[9]the tagger's words
content_tagsstatistical power analysis / effect size
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content_tags.statistics[10]the tagger's words
content_tagsmaximum margin linear classifier, cross-validated
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content_tags.statistics[11]1.0the tagger's words
content_tagspairwise phase consistency
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content_tags.statistics[12]1.0the tagger's words
content_tagsRayleigh's test
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content_tags.statistics[13]1.0the tagger's words
content_tagspost-hoc power analysis
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content_tags.statistics[14]1.0the tagger's words
content_tagsOptogenetically silencing vHPC-to-mPFC terminals during the sample run impairs delayed non-match-to-place performance in opsin-expressing mice, while the same silencing during the entire trial also impairs it and silencing during choice does not reach significance.
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content_tags.findings[0]the tagger's words
content_tagsSample-phase silencing again impaired performance, confirming the pathway is required during encoding.
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content_tags.findings[1]the tagger's words
content_tagsSilencing the pathway during the memory delay produced no significant behavioural impairment.
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content_tags.findings[2]the tagger's words
content_tagsPopulation decoding of the sample goal from mPFC units was abolished (reduced to chance) by terminal illumination in Arch-expressing mice but was unchanged in Arch-negative controls.
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content_tags.findings[3]the tagger's words
content_tagsSample-phase terminal inhibition removed the firing-rate increase that goal-selective mPFC units show at their preferred goal, while leaving their baseline rates intact.
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content_tags.findings[4]the tagger's words
content_tagsDuring choice runs the same goal-selective firing-rate elevation persisted despite terminal inhibition, so mPFC location coding at retrieval does not need the direct vHPC input.
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content_tags.findings[5]the tagger's words
content_tagsTerminal inhibition did not change overall mPFC firing rates, either pooled or split into putative pyramidal cells and interneurons.
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content_tags.findings[6]the tagger's words
content_tagsA decoder trained on no-light trials was unaffected when tested on sample-light trials, suggesting terminal inhibition does not generally interfere with encoding of task-relevant information.
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content_tags.findings[7]the tagger's words
content_tagsA subset of mPFC units phase-locked to vHPC gamma, and phase-locking was strongest at lags where vHPC gamma preceded mPFC spiking, indicating vHPC leads mPFC in the gamma band.
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content_tags.findings[8]the tagger's words
content_tagsInhibiting the vHPC-mPFC terminals weakened gamma phase-locking, showing the long-range gamma synchrony depends on the direct anatomical projection.
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content_tags.findings[9]the tagger's words
content_tagsIn the theta band the directionality reversed - mPFC led vHPC - and theta synchrony was not affected by silencing the pathway.
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content_tags.findings[10]the tagger's words
content_tagsGamma phase-locking was stronger during sample runs than choice runs, associating it with the encoding phase.
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content_tags.findings[11]the tagger's words
content_tagsAdditionally, gamma phase-locking during sample runs distinguished correct from incorrect trials.
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content_tags.findings[12]the tagger's words
content_tagsThe mPFC showed no retrospective coding of the previously visited location.
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content_tags.findings[13]the tagger's words
content_tagsinhibiting the direct pathway during the delay produced no significant impairment
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content_tags.findings[14]1.0the tagger's words
content_tagssample goal is decoded from prefrontal population activity at 96% on arrival at the goal
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content_tags.findings[15]1.0the tagger's words
content_tagsinhibiting the pathway during encoding drops that decoding to chance in opsin-expressing animals only
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content_tags.findings[16]1.0the tagger's words
content_tagsthe same manipulation leaves task-phase decoding unaffected, so it does not generally impair encoding
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content_tags.findings[17]1.0the tagger's words
content_tagsoverall mPFC firing rates are unchanged by terminal illumination
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content_tags.findings[18]1.0the tagger's words
content_tagsgoal selectivity during choice runs survives the same inhibition, mirroring the behaviour
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content_tags.findings[19]1.0the tagger's words
content_tagsa subset of mPFC units phase-lock to vHPC gamma, most at lags where vHPC gamma precedes mPFC spiking
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content_tags.findings[20]1.0the tagger's words
content_tagsin theta the direction reverses and synchrony is unaffected by the same manipulation
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content_tags.findings[21]1.0the tagger's words
content_tagsgamma phase-locking is stronger on sample than choice runs, and stronger on correct than incorrect trials
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content_tags.findings[22]1.0the tagger's words
content_tagsno retrospective location coding was found in mPFC during the delay
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content_tags.findings[23]1.0the tagger's words
content_tagsspatial working memory
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content_tags.definitions[0]the tagger's words
content_tagsvHPC
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also in: vHPC
content_tags.definitions[1]the tagger's words
content_tagssample phase
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also in: sample phase
content_tags.definitions[2]the tagger's words
content_tagsdelay phase
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also in: delay phase
content_tags.definitions[3]the tagger's words
content_tagspreferred goal
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content_tags.definitions[4]the tagger's words
content_tagsspatial working memory
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content_tags.definitions[5]0.9the tagger's words
content_tagslag analysis
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also in: lag analysis
content_tags.definitions[6]1.0the tagger's words
content_tagsopsin-negative control
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content_tags.variables[1]the tagger's words
content_tagsintra-trial delay
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content_tags.variables[2]the tagger's words
content_tagsfiring rate
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also in: firing rate
content_tags.variables[4]the tagger's words
content_tagsgamma phase-locking
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content_tags.variables[6]the tagger's words
content_tags4-goal T-maze
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also in: 4-goal T-maze
content_tags.variables[7]the tagger's words
content_tagssample goal identity
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content_tags.variables[9]1.0the tagger's words
content_tags792 — well-isolated mPFC single units recorded, from 9 mice
Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.
content_tags.quantities[0]the tagger's words
content_tags44% — share of mPFC single units showing selectivity for a spatial dimension distinguishing the goal arms
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content_tags.quantities[1]the tagger's words
content_tags96% — peak accuracy of decoding the sample goal from the mPFC population, at arrival at the reward port
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content_tags.quantities[2]the tagger's words
content_tags0.98 — accuracy of decoding task phase (sample vs choice) at the moment the start-box doors opened
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content_tags.quantities[3]the tagger's words
content_tags~40% — reduction of the vHPC-evoked postsynaptic multiunit response in mPFC by terminal illumination in Arch+ mice
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content_tags.quantities[4]the tagger's words
content_tags~50% — reduction of spontaneous multiunit activity when light was delivered to vHPC cell bodies (versus no effect on vHPC when only terminals were illuminated)
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content_tags.quantities[5]the tagger's words
content_tags1.48 — effect size for the behavioural impairment in Arch+ mice in the 4-goal experiment, with 90% power at N of 7
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content_tags.quantities[6]the tagger's words
content_tagsn of 37 animals/group — sample size a post-hoc power analysis says would be needed to detect the choice-phase effect
Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.
content_tags.quantities[7]the tagger's words
content_tagsfewer than 10% — proportion of mPFC units significantly phase-locked to vHPC gamma at the best lag
Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.
content_tags.quantities[8]the tagger's words
content_tagst=−3.91, p=0.001 — test of the performance difference between trials where sample and choice goals matched in the left/right dimension (0.65) and where they differed (0.71)
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about this quote: FLATTENED EXPONENT IN THIS QUOTE - THE NUMBER IS WRONG BY ORDERS OF MAGNITUDE AS IT STANDS. The staged text reads '4.0 × 10 3', where the paper writes 10 to the power 3. The superscript was pushed onto the line by the PDF extractor. The quote is verbatim to the staged text and its anchor is sound; the STAGED TEXT is what is damaged. NOT repaired - repair means re-staging the body and re-anchoring the record.
content_tags.quantities[9]the tagger's words
content_tags792 well-isolated single units from 9 mice, 44% spatially selective — the recorded sample
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content_tags.quantities[10]1.0the tagger's words
content_tagsabout 40% reduction in evoked response, about 50% reduction in local activity at the source — validation of the terminal inhibition
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content_tags.quantities[11]0.9the tagger's words
content_tags96% — peak decoding accuracy for sample goal
Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.
content_tags.quantities[12]1.0the tagger's words
content_tags0.98 — task-phase decoding accuracy, the specificity control
Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.
content_tags.quantities[13]0.9the tagger's words
content_tagsn of 37 animals per group — what would have been needed to detect the choice-phase effect - the null is quantified rather than asserted
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content_tags.quantities[14]1.0the tagger's words
content_tagseffect size 1.48, power 90% at N=7 and 83% at N=6 — the power behind the positive result
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content_tags.quantities[15]1.0the tagger's words
content_tagsfewer than 10% of mPFC units — how many were significantly phase-locked at the best lag
Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.
content_tags.quantities[16]1.0the tagger's words

Interpretive choices

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