Amygdala circuitry mediating reversible and bidirectional control of anxiety
Open accessAbstract
Anxiety—a sustained state of heightened apprehension in the absence of immediate threat—becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)—achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA—exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA–CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.
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- Findingown data
Optogenetic activation of BLA axon terminals within the CeA did not impair locomotion.
“without impaired locomotion (Supplementary Fig. 4)”
Quote in the paperSubstantial claim - Findingown data
A higher proportion of CeL neurons expressed c-fos in mice receiving ChR2:BLA-CeA stimulation than in eYFP:BLA-CeA controls.
“A higher proportion of CeL neurons expressed c-fos in the ChR2:BLA-CeA group relative to the eYFP:BLA-CeA group (F2,9=4.54, p=0.04)”
Quote in the paperSubstantial claim - Findingown data
Illumination of BLA terminals in the CeL elicited excitatory responses in both weakly- and strongly-connected CeL cells.
“Illumination of BLA terminals in CeL elicited excitatory responses in both weakly- and strongly-connected CeL cells (n=16; Fig. 2c).”
Quote in the paperSubstantial claim - Findingown data
In acute slices, time-locked light-evoked excitatory responses were abolished by bath application of NBQX and AP5.
“in acute slices time-locked light-evoked excitatory responses were abolished upon bath application of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f] quinoxaline-2,3-dione (NBQX) and (2R)-amino-5-phosphonopentanoate (AP5) (Supplementary Fig. 10).”
Quote in the paperSubstantial claim - Findingown data
Selective illumination of BLA-CeL synapses produced potent inhibition of spiking in CeM neurons.
“Indeed, we observed potent spiking inhibition in CeM cells upon illumination of BLA-CeL terminals (Fig. 2d; F2,11=15.35, p=0.004).”
Quote in the paperSubstantial claim
- Findingreasoning
Inhibition of BLA somata did not induce an anxiogenic response.
“BLA somata inhibition did not induce an anxiogenic response, perhaps owing to the simultaneous decrease in direct BLA-CeM excitatory input.”
Quote in the paperSubstantial claim - Findingown data
Optogenetic activation of BLA axon terminals within the CeA increased center time in the open-field test relative to eYFP controls, indicating reduced anxiety.
“as well as increased center time in the OFT (F1,105=24.46, p<0.00001; Fig. 1d,e), reflecting anxiety reduction”
Quote in the paperSubstantial claim - Findingown data
Optogenetic activation of BLA axon terminals within the CeA increased open-arm time on the elevated-plus maze relative to eYFP controls, indicating reduced anxiety.
“Photostimulation of BLA terminals in the CeA (ChR2:BLA-CeA) increased open-arm time (F1,42=69.09, p<0.00001; Fig. 1b,c)”
Quote in the paperSubstantial claim - Findingown data
In vivo illumination of BLA-CeA projections that produced acute anxiolysis excited CeL neurons without activating all BLA somata nonspecifically.
“Thus, the in vivo illumination of BLA-CeA projections that triggered acute anxiolysis was found to excite CeL neurons without activating all BLA somata nonspecifically.”
Quote in the paperSubstantial claim - Findingown data
The eNpHR3.0:BLA-CeA group showed elevated c-fos expression in the CeM relative to eYFP:BLA-CeA and eNpHR3.0:BLA(somata) groups.
“the eNpHR3.0:BLA-CeA group showed elevated levels of c-fos expression, relative to the eYFP:BLA-CeA and eNpHR3.0:BLA(somata) groups, in the CeM (p<0.05; Supplementary Fig. 12)”
Quote in the paperSubstantial claim - Findingown data
Optogenetic activation of BLA axon terminals within the CeA increased the probability of open-arm entry from the maze center on the elevated-plus maze.
“and probability of open-arm entry from the maze center (F1,42=24.69, p<0.00001: Fig. 1c inset; Supplementary Movie) on the EPM”
Quote in the paperSubstantial claim - Findingreasoning
The anxiolytic effect of BLA-CeA stimulation was not observed with direct optogenetic control of BLA somata.
“Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures.”
Quote in the paperSubstantial claim - Findingown data
Intra-CeA glutamate receptor antagonism abolished the light-induced reductions in anxiety measured by open-arm time, probability of open-arm entry, and center time.
“intra-CeA glutamate receptor antagonism abolished light-induced reductions in anxiety as measured by open-arm time (F1,35=8.61; p=0.008) and probability of open-arm entry on the EPM (F1,35=5.92, p=0.02), and center time during the OFT (F1,77=13.99; p=0.0006; Fig. 3c,d).”
Quote in the paperSubstantial claim - Findingown data
Optogenetically-driven vesicle release can occur in the absence of reliable antidromic action potential firing.
“The marked difference between effective synaptic transmission and antidromic spiking fidelity (p=0.0039; Fig. 3b, inset) reveals that optogenetically-driven vesicle release may occur in the absence of reliable antidromic drive”
Quote in the paperSubstantial claim - Study design and conductown data
eNpHR3.0 expression was restricted to glutamatergic neurons in the BLA.
“eNpHR3.0 expression was restricted to glutamatergic neurons in the BLA”
Quote in the paperSubstantial claim - Study design and conductown data
There were no group differences in the proportion of eYFP-positive cells within each region.
“No group differences were detected in the proportion of eYFP-positive cells within each region (Supplementary Fig. 5).”
Quote in the paperSubstantial claim - Interpretationown data
The balance of direct and indirect inputs from the BLA to the CeM can modulate CeM activity.
“These data from a structurally- and functionally-identified microcircuit25 illustrate that the balance of direct and indirect inputs from the BLA to the CeM can modulate CeM activity.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Davis, M. in The Amygdala: A Functional Analysis (ed. Aggleton, J. P. ) 213–288 (Oxford Univ. Press, 2000) source
Not checked in the free run.
- Study design and conductown data
Glutamate receptor antagonist treatment did not impair locomotor activity.
“Importantly, drug treatment did not impair locomotor activity (Supplementary Fig. 9)”
Quote in the paperSubstantial claim - Interpretationreasoning
Multiple subpopulations or projections of BLA neurons can act in opposition.
“suggests that multiple subpopulations or projections of BLA neurons can act in opposition (e.g. direct excitation of CeM along with feed-forward inhibition of CeM).”
Quote in the paperSubstantial claim - Interpretationown data
The BLA-CeL pathway is a neural substrate for real-time bidirectional modulation of unconditioned anxiety.
“Here, we have identified the BLA-CeL pathway as a neural substrate for real-time bidirectional modulation of the unconditioned expression of anxiety.”
Quote in the paperSubstantial claim - Premisecitation
BLA neurons excite GABAergic CeL neurons that provide feed-forward inhibition onto CeM output neurons.
“since BLA neurons excite GABAergic CeL neurons26 that provide feed-forward inhibition onto CeM “output” neurons6,18,19”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [26] Pitkanen, A. in The Amygdala: A Functional Analysis (ed. Aggleton, J. P. ) 31–99 (Oxford Univ. Press, 2000) source
Not checked in the free run.
- cites [6] Pare, D., Quirk, G. J. & Ledoux, J. E. New vistas on amygdala networks in conditioned fear. J. Neurophysiol. 92, 1–9 (2004) source
Not checked in the free run.
- cites [18] Ciocchi, S. et al. Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468, 277–282 (2010) source
Not checked in the free run.
- cites [19] Haubensak, W. et al. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468, 270–276 (2010) source
Not checked in the free run.
- Interpretationown data
Anxiety is continuously regulated by balanced antagonistic pathways within the amygdala.
“these findings demonstrate that anxiety is continuously regulated by balanced antagonistic pathways within the amygdala”
Quote in the paperSubstantial claim - Interpretationown data
Inhibition of BLA-CeL synapses suppresses feed-forward inhibition from CeL neurons to CeM neurons, thereby increasing CeM excitability and downstream anxiety.
“consistent with the hypothesis that inhibition of BLA-CeL synapses suppresses feed-forward inhibition from CeL neurons to CeM neurons, thereby increasing CeM excitability and the downstream processes leading to increased anxiety phenotypes.”
Quote in the paperSubstantial claim
- May combine two claims. 9
- Classified as probably not a substantial claim. 5
May combine two claims.
Findingown dataSelective illumination of eNpHR3.0-expressing axon terminals reduced spontaneous and electrically-evoked vesicle release without preventing somatic spiking.
“Selective illumination of eNpHR3.0-expressing axon terminals reduced the probability of both spontaneously occurring (frequency: F1,8=32.99, p=0.00024; amplitude: F1,8=21.96, p=0.001; Supplementary Fig. 13) and electrically-evoked (F1,10=10.79, p=0.006; Fig. 4a) vesicle release, without preventing spiking at the soma (Supplementary Fig. 14).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAmong sampled BLA neurons, 44% projected to the CeL alone, 17% projected to the CeM alone, and only one cell projected to both the CeL and the CeM.
“Of the BLA neurons sampled (n=18, Supplementary Fig. 7); 44% projected to the CeL alone and 17% projected to the CeM alone, with only one cell observed to project to both the CeL and the CeM.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe same CeM neurons showed net excitation upon broad illumination of BLA inputs to the CeM but net inhibition upon selective illumination of BLA inputs to the CeL.
“the very same CeM neurons (n=7) showed net excitation upon broad illumination of BLA inputs to the CeM (Fig. 2e), but showed net inhibition upon selective illumination of BLA inputs to the CeL (Fig. 2f).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataSelective optogenetic inhibition of BLA-CeA terminals with eNpHR3.0 reduced open-arm time, probability of open-arm entry, and center time, indicating increased anxiety-like behavior.
“We also found that the eNpHR3.0:BLA-CeA group showed reduced open-arm time and probability of open-arm entry on EPM (F1,40=21.08, p<0.00001; and F1,40=19.93, p<0.00001, respectively; Fig. 4b,c) and center-time in the OFT (F1,100=18.919, p<0.00001; Fig. 4d,e) during photostimulation when compared to the eYFP and BLA(somata) groups, without altering locomotor activity”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe CeM is the primary output region of the amygdala and, when excited, mediates autonomic and behavioral fear and anxiety responses via brainstem projections.
“The primary output region of the amygdala is the CeM23,24 which (when chemically or electrically excited) mediates autonomic and behavioral responses associated with fear and anxiety via projections to the brainstem25.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [23] Krettek, J. E. & Price, J. L. A description of the amygdaloid complex in the rat and cat with observations on intra-amygdaloid axonal connections. J. Comp. Neurol. 178, 255–279 (1978) source
Not checked in the free run.
- cites [24] Krettek, J. E. & Price, J. L. Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat. J. Comp. Neurol. 178, 225–253 (1978) source
Not checked in the free run.
- cites [25] Davis, M. in The Amygdala: A Functional Analysis (ed. Aggleton, J. P. ) 213–288 (Oxford Univ. Press, 2000) source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe findings do not exclude downstream or parallel circuits including the BNST, insular and prefrontal cortices, and the septal-hippocampal circuit.
“our findings do not exclude downstream or parallel circuits including the BNST28, the insular and prefrontal cortices29, and the septal-hippocampal circuit30”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [28] Davis, M., Walker, D. L., Miles, L. & Grillon, C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105–135 (2010) source
Not checked in the free run.
- cites [29] Shin, L. M. & Liberzon, I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35, 169–191 (2010) source
Not checked in the free run.
- cites [30] Gray, J. A. & McNaughton, N. The neuropsychology of anxiety: reprise. Nebr. Symp. Motiv. 43, 61–134 (1996)
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenQuantitative analyses of confocal images were performed with staining and analysis blind to experimental condition.
“Quantitative analyses of confocal images were performed with both staining and analysis blind to experimental condition.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe bevelled cannula shielding effectively prevented BLA somata photostimulation, as indicated by no detectable difference in c-fos-positive BLA cells between ChR2:BLA-CeA and eYFP:BLA-CeA groups.
“but no detectable difference between the ChR2:BLA-CeA and eYFP:BLA-CeA groups, indicating that the bevelled cannula shielding effectively prevented BLA somata photostimulation.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe BLA is primarily glutamatergic, and the CeA consists mostly of GABAergic medium spiny neurons.
“The BLA is primarily glutamatergic (~90%)20, 21 while the CeA, which encompasses the centrolateral (CeL) and centromedial (CeM) nuclei, consists of ~95% GABAergic medium spiny neurons22.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [20] Carlsen, J. Immunocytochemical localization of glutamate decarboxylase in the rat basolateral amygdaloid nucleus, with special reference to GABAergic innervation of amygdalostriatal projection neurons. J. Comp. Neurol. 273, 513–526 (1988) source
Not checked in the free run.
- cites [21] Smith, Y. & Pare, D. Intra-amygdaloid projections of the lateral nucleus in the cat: PHA-L anterograde labeling combined with postembedding GABA and glutamate immunocytochemistry. J. Comp. Neurol. 342, 232–248 (1994) source
Not checked in the free run.
- cites [22] McDonald, A. J. Cytoarchitecture of the central amygdaloid nucleus of the rat. J. Comp. Neurol. 208, 401–418 (1982) source
Not checked in the free run.
May combine two claims.
Study design and conductown dataOpsin expression was specific to BLA glutamatergic neurons and was not observed in intercalated cells.
“Opsin expression was specific to BLA glutamatergic neurons, and was not observed in intercalated cells (Supplementary Fig. 6).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe findings are consistent with prior reports implicating the CeA in anxiety.
“These data are consistent with reports implicating CeA involvement in anxiety9,11,12”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [9] Kalin, N. H., Shelton, S. E. & Davidson, R. J. The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J. Neurosci. 24, 5506–5515 (2004) source
Not checked in the free run.
- cites [11] Etkin, A., Prater, K. E., Schatzberg, A. F., Menon, V. & Greicius, M. D. Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch. Gen. Psychiatry 66, 1361–1372 (2009) source
Not checked in the free run.
- cites [12] Lyons, A. M. & Thiele, T. E. Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice. Peptides 31, 2193–2199 (2010) source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationStress induces CeL release of corticotropin releasing hormone in the BNST.
“for example, stress induces CeL release of corticotropin releasing hormone (CRH) in the BNST28.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Davis, M., Walker, D. L., Miles, L. & Grillon, C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105–135 (2010) source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe light-induced anxiolytic effects were caused by activation of BLA-CeA synapses rather than by BLA projections to distal targets passing through the CeA.
“These data demonstrate that the light-induced anxiolytic effects were caused by the activation of BLA-CeA synapses, and not attributable to BLA projections to distal targets passing through the CeA.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductcitationThe elevated-plus maze and open-field test are well-validated assays for anxiety-related behavior.
“two well-validated27 anxiety assays: the elevated-plus maze (EPM) and the open-field test (OFT; Fig. 1a–e).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Carola, V., D’Olimpio, F., Brunamonti, E., Mangia, F. & Renzi, P. Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav. Brain Res. 134, 49–57 (2002) source
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Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Conventionally used AAV backbones with a 1.3 kb CaMKIIα promoter, WPRE, and human growth hormone polyadenylation signal have a capacity of 2.4 kb.
“Conventionally used AAV backbones which include a commonly used neuronal expression cassette composed of 1.3 kb CaMKIIα promoter (which shows comparable expression efficiency with 0.4 kb CaMKIIα promoter [10] used in CWB), WPRE, and human growth hormone polyadenylation signal [23-25] has a capacity of 2.4 kb.”
From Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons (2014) · cites this paper as [23]
The Methods Summary (Virus-mediated opsin gene expression; page not provided) describes AAV5-packaged plasmids using a CaMKIIα promoter. It does not specify a 1.3 kb promoter, WPRE, a human growth hormone polyadenylation signal, or a 2.4 kb capacity; searches for those cassette components and capacity found no supporting passage. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe amygdala also regulates anxiety.
“In addition to a role in fear and threat conditioning, the amygdala also regulates anxiety.”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Tye et al., 2011
The neural systems implicated in anxiety by rodent studies are consistent with those identified in human patients.
“This contrast notwithstanding, the neural systems implicated in anxiety by rodent studies are consistent with those identified in human patients26-34, underscoring the utility and translatability of these rodent studies.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [33]
Photoactivation of BLA somata increases measures of innate anxiety, as well as learned inhibitory avoidance.
“Moreover, photoactivation of BLA somata increases measures of innate anxiety33, as well as learned inhibitory avoidance80.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [33]
Photostimulation of excitatory basolateral amygdala projections to the central amygdala resulted in an acute anxiolytic effect that rapidly dissipated upon cessation of stimulation.
“For example, photostimulation of excitatory basolateral amygdala projections to central amygdala resulted in an acute anxiolytic effect that rapidly dissipated upon cessation of stimulation (Tye et al., 2011).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Tye et al., 2011
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Gründemann, J., Bitterman, Y., Lu, T., Krabbe, S., Grewe, B. F., Schnitzer, M. J., & Lüthi, A. (2019) · Science · doi:10.1126/science.aav8736 · Cited by 223 · see citing works
β-catenin mediates stress resilience through Dicer1/microRNA regulation
Dias, C., Feng, J., Sun, H., Shao, N. Y., Mazei-Robison, M. S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonté, B., Ribeiro, E., et al. (2014) · Nature · doi:10.1038/nature13976 · Cited by 240 · see citing works
- Authors
- Tye, K. M., Prakash, R., Kim, S.-Y., Fenno, L. E., Grosenick, L., Zarabi, H., Thompson, K. R., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K.
- Affiliations
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Deisseroth, Karl
- ORCID
- Venue
- Nature
- Published
- 2011-03
- Volume
- 471
- Issue
- 7338
- Pages
- 358-362
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3154022
- OpenAlex
- W2060978874
- Semantic Scholar
- ffc80185f7540e58c28aead0cf3752801f320eb3
- Cited by
- 1,289
- References
- 32
- Citations by year
- 2026: 62 · 2025: 73 · 2024: 86 · 2023: 73 · 2022: 76 · 2021: 97 · 2020: 91 · 2019: 84 · 2018: 85 · 2017: 70 · 2016: 100 · 2015: 97 · 2014: 92 · 2013: 76 · 2012: 87
- FWCI
- 47.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Institutes of Health (DP1OD000616)
- National Institute of Mental Health (F32MH088010, R01MH075957)
- National Institute on Drug Abuse (R01DA020794)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- anxiety, amygdala, central amygdala, basolateral amygdala, neural circuits, anxiolytic effects, bidirectional control, optogenetic stimulation, optogenetic inhibition, channelrhodopsin, halorhodopsin, fear memory, anxiety disorders, rats, mice
- MeSH terms
- Amygdala, Animals, Anxiety, Anxiety Disorders, Light, Models, Neurological, Neural Pathways, Neurons, Stress, Physiological, Synapses, Halorhodopsins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.
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