CoChat
Sign Up
Cited by 170Memory and Neural MechanismsNeural dynamics and brain functionNeuroscience of respiration and sleep

Olfactory inputs modulate respiration-related rhythmic activity in the prefrontal cortex and freezing behavior

Open access
Moberly, Andrew H., Schreck, Mary, Bhattarai, Janardhan P., Zweifel, Larry S., Luo, Wenqin, Ma, Minghong·2018·Nature Communications
DOI 10.1038/s41467-018-03988-1PMC PMC5906445
Open this paper in CoChat — free accountOpen PDF

Abstract

Respiration and airflow through the nasal cavity are known to be correlated with rhythmic neural activity in the central nervous system. Here we show in rodents that during conditioned fear-induced freezing behavior, mice breathe at a steady rate (~4 Hz), which is correlated with a predominant 4-Hz oscillation in the prelimbic prefrontal cortex (plPFC), a structure critical for expression of conditioned fear behaviors. We demonstrate anatomical and functional connections between the olfactory pathway and plPFC via circuit tracing and optogenetics. Disruption of olfactory inputs significantly reduces the 4-Hz oscillation in the plPFC, but leads to prolonged freezing periods. Our results indicate that olfactory inputs can modulate rhythmic activity in plPFC and freezing behavior.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-018-03988-1

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • The coupling between nasal respiration and neural activity in limbic regions is associated with the modulation of memory performance and of emotional ratings in humans, and it influences freezing behavior in mice.

    “The coupling between nasal respiration and neural activity in limbic regions is also associated with the modulation of memory performance 120,138,139 and of emotional ratings in humans 120 , and it influences freezing behavior in mice 134,135 .”

    From Interoceptive rhythms in the brain (2023) · cites this paper as [135]

  • Respiration also modulates neural activity in medial prefrontal cortex in rodents.

    “Respiration also modulates neural activity in medial prefrontal cortex in rodents 130,133-135 ,”

    From Interoceptive rhythms in the brain (2023) · cites this paper as [135]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 55

  1. [1]Feldman JL Del Negro CA Gray PA Understanding the rhythm of breathing: so near, yet so far Annu Rev. Physiol. 2013 75 423 452 10.1146/annurev-physiol-040510-130049 23121137 PMC3671763 · DOI
  2. [2]Yackle K Breathing control center neurons that promote arousal in mice Science 2017 355 1411 1415 10.1126/science.aai7984 28360327 PMC5505554 · DOI · Paper page
  3. [3]Buonviso N Amat C Litaudon P Respiratory modulation of olfactory neurons in the rodent brain Chem. Senses 2006 31 145 154 10.1093/chemse/bjj010 16339270 · DOI
  4. [4]Carlson KS Dillione MR Wesson DW Odor- and state-dependent olfactory tubercle local field potential dynamics in awake rats J. Neurophysiol. 2014 111 2109 2123 10.1152/jn.00829.2013 24598519 · DOI
  5. [5]Fontanini A Spano P Bower JM Ketamine-xylazine-induced slow (1.5 Hz) oscillations in the rat piriform (olfactory) cortex are functionally correlated with respiration J. Neurosci. 2003 23 7993 8001 12954860 PMC6740491
  6. [6]Connelly T G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons Proc. Natl Acad. Sci. USA 2015 112 590 595 10.1073/pnas.1418515112 25550517 PMC4299258 · DOI
  7. [8]Iwata R Kiyonari H Imai T Mechanosensory-based phase coding of odor identity in the olfactory bulb Neuron 2017 96 1139 1152 e1137 10.1016/j.neuron.2017.11.008 29216451 · DOI
  8. [9]Wu R Liu Y Wang L Li B Xu F Activity patterns elicited by airflow in the olfactory bulb and their possible functions J. Neurosci. 2017 37 10700 10711 28972124 PMC6596515
  9. [10]Onoda N Mori K Depth distribution of temporal firing patterns in olfactory-bulb related to air-intake cycles J. Neurophysiol. 1980 44 29 39 10.1152/jn.1980.44.1.29 7420137 · DOI
  10. [11]Phillips ME Sachdev RN Willhite DC Shepherd GM Respiration drives network activity and modulates synaptic and circuit processing of lateral inhibition in the olfactory bulb J. Neurosci. 2012 32 85 98 10.1523/JNEUROSCI.4278-11.2012 22219272 PMC3566643 · DOI
  11. [12]Biskamp J Bartos M Sauer JF Organization of prefrontal network activity by respiration-related oscillations Sci. Rep. 2017 7 45508 10.1038/srep45508 28349959 PMC5368652 · DOI · Paper page
  12. [14]Nguyen Chi V HippocaMpal respiration-driven rhythm distinct from theta oscillations in awake mice J. Neurosci. 2016 36 162 177 10.1523/JNEUROSCI.2848-15.2016 26740658 PMC6601786 · DOI · Paper page
  13. [15]Yanovsky Y Ciatipis M Draguhn A Tort AB Brankack J Slow oscillations in the mouse hippocampus entrained by nasal respiration J. Neurosci. 2014 34 5949 5964 10.1523/JNEUROSCI.5287-13.2014 24760854 PMC6608283 · DOI · Paper page
  14. [16]Kleinfeld D Deschenes M Wang F Moore JD More than a rhythm of life: breathing as a binder of orofacial sensation Nat. Neurosci. 2014 17 647 651 10.1038/nn.3693 24762718 PMC4140942 · DOI
  15. [17]Jensen O Colgin LL Cross-frequency coupling between neuronal oscillations Trends Cogn. Sci. 2007 11 267 269 10.1016/j.tics.2007.05.003 17548233 · DOI · Paper page
  16. [18]Varela F Lachaux JP Rodriguez E Martinerie J The brainweb: phase synchronization and large-scale integration Nat. Rev. Neurosci. 2001 2 229 239 10.1038/35067550 11283746 · DOI · Paper page
  17. [19]Likhtik E Stujenske JM Topiwala MA Harris AZ Gordon JA Prefrontal entrainment of amygdala activity signals safety in learned fear and innate anxiety Nat. Neurosci. 2014 17 106 113 10.1038/nn.3582 24241397 PMC4035371 · DOI · Paper page
  18. [20]Seidenbecher T Laxmi TR Stork O Pape HC Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval Science 2003 301 846 850 10.1126/science.1085818 12907806 · DOI · Paper page
  19. [21]Dejean C Prefrontal neuronal assemblies temporally control fear behaviour Nature 2016 535 420 424 10.1038/nature18630 27409809 · DOI
  20. [22]Karalis N 4-Hz oscillations synchronize prefrontal-amygdala circuits during fear behavior Nat. Neurosci. 2016 19 605 612 10.1038/nn.4251 26878674 PMC4843971 · DOI
  21. [23]Greenberg T Carlson JM Cha J Hajcak G Mujica-Parodi LR Ventromedial prefrontal cortex reactivity is altered in generalized anxiety disorder during fear generalization Depress Anxiety 2013 30 242 250 10.1002/da.22016 23139148 · DOI
  22. [24]Lei HM Mooney R Katz LC Synaptic integration of olfactory information in mouse anterior olfactory nucleus J. Neurosci. 2006 26 12023 12032 10.1523/JNEUROSCI.2598-06.2006 17108176 PMC6674854 · DOI
  23. [25]Kay LM Circuit oscillations in odor perception and memory Prog. Brain Res. 2014 208 223 251 10.1016/B978-0-444-63350-7.00009-7 24767485 · DOI
  24. [26]Rojas-Libano D Frederick DE Egana JI Kay LM The olfactory bulb theta rhythm follows all frequencies of diaphragmatic respiration in the freely behaving rat Front Behav. Neurosci. 2014 8 214 24966821 PMC4053074
  25. [27]Corcoran KA Quirk GJ Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears J. Neurosci. 2007 27 840 844 10.1523/JNEUROSCI.5327-06.2007 17251424 PMC6672908 · DOI
  26. [28]Courtin J Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression Nature 2014 505 92 96 10.1038/nature12755 24256726 · DOI · Paper page
  27. [29]Do-Monte FH Quinones-Laracuente K Quirk GJ A temporal shift in the circuits mediating retrieval of fear memory Nature 2015 519 460 463 10.1038/nature14030 25600268 PMC4376623 · DOI · Paper page
  28. [31]Ongur D Price JL The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans Cereb. Cortex 2000 10 206 219 10.1093/cercor/10.3.206 10731217 · DOI · Paper page
  29. [32]DeNardo LA Berns DS DeLoach K Luo L Connectivity of mouse somatosensory and prefrontal cortex examined with trans-synaptic tracing Nat. Neurosci. 2015 18 1687 1697 10.1038/nn.4131 26457553 PMC4624522 · DOI
  30. [33]Hoover WB Vertes RP Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat Brain Struct. Funct. 2007 212 149 179 10.1007/s00429-007-0150-4 17717690 · DOI · Paper page
  31. [34]Igarashi KM Parallel mitral and tufted cell pathways route distinct odor information to different targets in the olfactory cortex J. Neurosci. 2012 32 7970 7985 10.1523/JNEUROSCI.0154-12.2012 22674272 PMC3636718 · DOI
  32. [35]Suzukawa K Age-related changes of the regeneration mode in the mouse peripheral olfactory system following olfactotoxic drug methimazole-induced damage J. Comp. Neurol. 2011 519 2154 2174 10.1002/cne.22611 21452219 · DOI
  33. [36]Hendriksen H Korte SM Olivier B Oosting RS The olfactory bulbectomy model in mice and rat: one story or two tails? Eur. J. Pharmacol. 2015 753 105 113 10.1016/j.ejphar.2014.10.033 25446558 · DOI
  34. [37]Song C Leonard BE The olfactory bulbectomised rat as a model of depression Neurosci. Biobehav Rev. 2005 29 627 647 10.1016/j.neubiorev.2005.03.010 15925697 · DOI
  35. [38]Mori K Manabe H Narikiyo K Onisawa N Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex Front Psychol. 2013 4 743 10.3389/fpsyg.2013.00743 24137148 PMC3797617 · DOI
  36. [39]Nagayama S Takahashi YK Yoshihara Y Mori K Mitral and tufted cells differ in the decoding manner of odor maps in the rat olfactory bulb J. Neurophysiol. 2004 91 2532 2540 10.1152/jn.01266.2003 14960563 · DOI
  37. [40]Courtiol E Wilson DA The olfactory mosaic: bringing an olfactory network together for odor perception Perception 2017 46 320 332 10.1177/0301006616663216 27687814 PMC5362339 · DOI
  38. [41]Kocsis B Pittman-Polletta BR Roy A Respiration-coupled rhythms in prefrontal cortex: beyond if, to when, how, and why Brain Struct. Funct. 2018 223 11 16 10.1007/s00429-017-1587-8 29222723 PMC5794025 · DOI
  39. [42]Chen Y Anxiety- and depressive-like behaviors in olfactory deficient Cnga2 knockout mice Behav. Brain Res. 2014 275 219 224 10.1016/j.bbr.2014.08.042 25192635 · DOI
  40. [43]Glinka ME Olfactory deficits cause anxiety-like behaviors in mice J. Neurosci. 2012 32 6718 6725 10.1523/JNEUROSCI.4287-11.2012 22573694 PMC3367161 · DOI
  41. [44]Homma I Masaoka Y Breathing rhythms and emotions Exp. Physiol. 2008 93 1011 1021 10.1113/expphysiol.2008.042424 18487316 · DOI
  42. [45]Brown RP Gerbarg PL Yoga breathing, meditation, and longevity Ann. N. Y Acad. Sci. 2009 1172 54 62 10.1111/j.1749-6632.2009.04394.x 19735239 · DOI · Paper page
  43. [47]Philippot P Chapelle G Blairy S Respiratory feedback in the generation of emotion Cogn. Emot. 2002 16 605 627 10.1080/02699930143000392 · DOI · Paper page
  44. [48]Zelano C Nasal respiration entrains human limbic oscillations and modulates cognitive function J. Neurosci. 2016 36 12448 12467 10.1523/JNEUROSCI.2586-16.2016 27927961 PMC5148230 · DOI · Paper page
  45. [49]Li J Ishii T Feinstein P Mombaerts P Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons Nature 2004 428 393 399 10.1038/nature02433 15042081 · DOI
  46. [50]Madisen L A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing Nat. Neurosci. 2012 15 793 802 10.1038/nn.3078 22446880 PMC3337962 · DOI · Paper page
  47. [51]Harris JA Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation Front Neural Circuits 2014 8 76 10.3389/fncir.2014.00076 25071457 PMC4091307 · DOI · Paper page
  48. [52]Paxinos G., Franklin, K. B. J. The mouse brainin stereotaxic coordinates (Elsevier Academic Press, Cambridge, 2004).
  49. [53]McAfee SS Minimally invasive highly precise monitoring of respiratory rhythm in the mouse using an epithelial temperature probe J. Neurosci. Methods 2016 263 89 94 10.1016/j.jneumeth.2016.02.007 26868731 PMC4801653 · DOI
  50. [54]Hnasko TS Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia Proc. Natl Acad. Sci. USA 2006 103 8858 8863 10.1073/pnas.0603081103 16723393 PMC1466546 · DOI
  51. [55]Gore BB Soden ME Zweifel LS Manipulating gene expression in projection-specific neuronal populations using combinatorial viral approaches Curr. Protoc. Neurosci. 2013 65 1 20 PMC4242517 25429312
  52. [57]Mitra P. P. & Bokil, H. Observed Brain Dynamics (Oxford University Press, New York, 2008).
  53. [58]Kajikawa Y Schroeder CE How local Is the local field potential? Neuron 2011 72 847 858 10.1016/j.neuron.2011.09.029 22153379 PMC3240862 · DOI
  54. [59]Chen H Kohno K Gong Q Conditional ablation of mature olfactory sensory neurons mediated by diphtheria toxin receptor J. Neurocytol. 2005 34 37 47 10.1007/s11068-005-5046-8 16374708 · DOI
  55. [60]Goldstein BJ Schwob JE Analysis of the globose basal cell compartment in rat olfactory epithelium using GBC-1, a new monoclonal antibody against globose basal cells J. Neurosci. 1996 16 4005 4016 10.1523/JNEUROSCI.16-12-04005.1996 8656294 PMC6578610 · DOI

Cited by

Sorted by citations

Authors
Moberly, A. H., Schreck, M., Bhattarai, J. P., Zweifel, L. S., Luo, W., & Ma, M.
Affiliations
  • University of Pennsylvania (US)
  • University of Washington (US)
Corresponding author
Moberly, Andrew H.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-04-18
Volume
9
Issue
1
Pages
1528-1528
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-03988-1
PMC
PMC5906445
OpenAlex
W2800238864
Cited by
170
References
5
Citations by year
2026: 12 · 2025: 23 · 2024: 18 · 2023: 13 · 2022: 26 · 2021: 43 · 2020: 17 · 2019: 12 · 2018: 5 · 2017: 1
FWCI
11.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Science Foundation (1515930)
  • National Institutes of Health (5t32mh017168-34)
  • National Institute of Mental Health (T32 MH-017168)
  • National Institute on Deafness and Other Communication Disorders (R01DC006213)
  • National Institute of Neurological Disorders and Stroke (R01NS083702)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
olfactory pathway, prelimbic cortex, fear conditioning, freezing behavior, respiratory rhythm, neural oscillations, olfactory input, fear expression
MeSH terms
Animals, Extinction, Psychological, Fear, Female, Immunohistochemistry, Limbic System, Male, Mice, Inbred C57BL, Neurons, Olfactory Pathways, Periodicity, Respiration, Smell, Prefrontal Cortex, Mice, Optogenetics

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review