{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:12:16Z","timestamp":1789809136940,"version":"4.0.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH132223"],"award-info":[{"award-number":["MH132223"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH115947"],"award-info":[{"award-number":["MH115947"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Brain Struct Funct"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Circadian rhythms exert widespread influences on learning and memory processes across diverse brain regions. The extinction of emotional memories is enhanced when training and testing occur during the circadian active phase in both rodents and humans, yet the underlying neural mechanisms remain poorly understood. Here, we examined time-of-day differences in conditioned fear extinction memory and associated neural activity within the ventromedial prefrontal cortex (vmPFC), including within a vmPFC-to-basolateral\/basomedial amygdala (BLA\/BMA) pathway in rats. Using an intersectional viral strategy to label vmPFC to BLA\/BMA projection neurons, we found that female rats trained and tested during their active phase exhibited superior extinction recall compared to rats trained and tested during their inactive phase. The superior extinction recall was associated with greater FOS expression throughout the vmPFC, including within vmPFC to BLA\/BMA projection neurons. In a follow-up experiment, we examined dendritic spine morphology in untrained female and male rats. We observed greater dendritic spine density in vmPFC to BLA\/BMA neurons during the active phase compared to inactive phase, with this difference driven primarily by increased thin and stubby spine subtypes. These findings demonstrate that superior active phase extinction memory is associated with enhanced vmPFC circuit activity and corresponds to time-of-day differences in dendritic spine density within extinction-relevant neural pathways. Our results reveal a potential structural plasticity mechanism by which circadian rhythms modulate fear extinction learning and memory.<\/jats:p>","DOI":"10.1007\/s00429-026-03176-8","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:24:08Z","timestamp":1789806248000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Daily rhythms in fear extinction memory reflect structural and functional changes in a prefrontal-amygdala circuit"],"prefix":"10.1007","volume":"231","author":[{"given":"Noah R. R.","family":"Andrys","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan B.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A.","family":"Millisor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breyton K.","family":"McDole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-1994","authenticated-orcid":false,"given":"Michael V.","family":"Baratta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5563-6637","authenticated-orcid":false,"given":"Jason J.","family":"Radley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3120-6303","authenticated-orcid":false,"given":"Robert L.","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"3176_CR1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature15698","volume":"527","author":"A Adhikari","year":"2015","unstructured":"Adhikari A, Lerner TN, Finkelstein J et al (2015) Basomedial amygdala mediates top-down control of anxiety and fear. Nature 527:179\u2013185. https:\/\/doi.org\/10.1038\/nature15698","journal-title":"Nature"},{"key":"3176_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.01003","volume":"10","author":"A Agorastos","year":"2020","unstructured":"Agorastos A, Nicolaides NC, Bozikas VP et al (2020) Multilevel interactions of stress and circadian system: implications for traumatic stress. Front Psychiatry 10:1003. https:\/\/doi.org\/10.3389\/fpsyt.2019.01003","journal-title":"Front Psychiatry"},{"key":"3176_CR3","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.1002\/cne.24027","volume":"524","author":"RM Anderson","year":"2016","unstructured":"Anderson RM, Glanz RM, Johnson SB et al (2016) Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex. J Comp Neurol 524:3729\u20133746. https:\/\/doi.org\/10.1002\/cne.24027","journal-title":"J Comp Neurol"},{"key":"3176_CR4","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1093\/cercor\/bhz092","volume":"30","author":"RM Anderson","year":"2020","unstructured":"Anderson RM, Johnson SB, Lingg RT et al (2020) Evidence for similar prefrontal structural and functional alterations in male and female rats following chronic stress or glucocorticoid exposure. Cereb Cortex 30:353\u2013370. https:\/\/doi.org\/10.1093\/cercor\/bhz092","journal-title":"Cereb Cortex"},{"key":"3176_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5","volume":"7","author":"P Bankhead","year":"2017","unstructured":"Bankhead P, Loughrey MB, Fern\u00e1ndez JA et al (2017) QuPath: open source software for digital pathology image analysis. Sci Rep 7:16878. https:\/\/doi.org\/10.1038\/s41598-017-17204-5","journal-title":"Sci Rep"},{"key":"3176_CR6","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1007\/s00429-019-01875-z","volume":"224","author":"MV Baratta","year":"2019","unstructured":"Baratta MV, Gruene TM, Dolzani SD et al (2019) Controllable stress elicits circuit-specific patterns of prefrontal plasticity in males, but not females. Brain Struct Funct 224:1831\u20131843. https:\/\/doi.org\/10.1007\/s00429-019-01875-z","journal-title":"Brain Struct Funct"},{"key":"3176_CR7","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1126\/science.aah4965","volume":"354","author":"J Bass","year":"2016","unstructured":"Bass J, Lazar MA (2016) Circadian time signatures of fitness and disease. Sci (New York NY) 354:994\u2013999. https:\/\/doi.org\/10.1126\/science.aah4965","journal-title":"Sci (New York NY)"},{"key":"3176_CR8","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1093\/cercor\/bhw406","volume":"28","author":"T Bering","year":"2018","unstructured":"Bering T, Carstensen MB, W\u00f6rtwein G et al (2018) The circadian oscillator of the cerebral cortex: molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons. Cerebral cortex (New York, NY\u202f: 1991) 28:644\u2013657. https:\/\/doi.org\/10.1093\/cercor\/bhw406","journal-title":"Cerebral cortex (New York, NY : 1991)"},{"key":"3176_CR9","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41398-018-0106-x","volume":"8","author":"DW Bloodgood","year":"2018","unstructured":"Bloodgood DW, Sugam JA, Holmes A, Kash TL (2018) Fear extinction requires infralimbic cortex projections to the basolateral amygdala. Translational psychiatry 8:60. https:\/\/doi.org\/10.1038\/s41398-018-0106-x","journal-title":"Translational psychiatry"},{"key":"3176_CR10","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2020","author":"ME Bouton","year":"2020","unstructured":"Bouton ME, Maren S, McNally GP (2020) Behavioral and Neurobiological Mechanisms of Pavlovian and Instrumental Extinction Learning. Physiol Rev. https:\/\/doi.org\/10.1152\/physrev.00016.2020","journal-title":"Physiol Rev"},{"key":"3176_CR11","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1080\/03610928708829405","volume":"16","author":"EH Brittain","year":"1987","unstructured":"Brittain EH (1987) P-values for the multi-sample kolmogorov-smirnov test using the expanded bonferroni appoximation. Commun Stat - Theory Methods 16:821\u2013835. https:\/\/doi.org\/10.1080\/03610928708829405","journal-title":"Commun Stat - Theory Methods"},{"key":"3176_CR12","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500251","volume":"1","author":"O Bukalo","year":"2015","unstructured":"Bukalo O, Pinard CR, Silverstein S et al (2015) Prefrontal inputs to the amygdala instruct fear extinction memory formation. Sci Adv 1:e1500251. https:\/\/doi.org\/10.1126\/sciadv.1500251","journal-title":"Sci Adv"},{"key":"3176_CR13","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.neuron.2007.02.021","volume":"53","author":"A Burgos-Robles","year":"2007","unstructured":"Burgos-Robles A, Vidal-Gonzalez I, Santini E, Quirk GJ (2007) Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex. Neuron 53:871\u2013880. https:\/\/doi.org\/10.1016\/j.neuron.2007.02.021","journal-title":"Neuron"},{"key":"3176_CR14","doi-asserted-by":"publisher","first-page":"30710","DOI":"10.1073\/pnas.2000942117","volume":"117","author":"BC Campbell","year":"2020","unstructured":"Campbell BC, Nabel EM, Murdock MH et al (2020) mGreenLantern: a bright monomeric fluorescent protein with rapid expression and cell filling properties for neuronal imaging. Proc Natl Acad Sci 117:30710\u201330721. https:\/\/doi.org\/10.1073\/pnas.2000942117","journal-title":"Proc Natl Acad Sci"},{"key":"3176_CR15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0166-4328(01)00471-5","volume":"133","author":"D Chaudhury","year":"2002","unstructured":"Chaudhury D, Colwell CS (2002) Circadian modulation of learning and memory in fear-conditioned mice. Behav Brain Res 133:95\u2013108","journal-title":"Behav Brain Res"},{"key":"3176_CR16","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1177\/0748730415598608","volume":"30","author":"LE Chun","year":"2015","unstructured":"Chun LE, Woodruff ER, Morton S et al (2015) Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats. J Biol Rhythm 30:417\u2013436. https:\/\/doi.org\/10.1177\/0748730415598608","journal-title":"J Biol Rhythm"},{"key":"3176_CR17","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1523\/jneurosci.5327-06.2007","volume":"27","author":"KA Corcoran","year":"2007","unstructured":"Corcoran KA, Quirk GJ (2007) Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. J Neurosci 27:840\u2013844. https:\/\/doi.org\/10.1523\/jneurosci.5327-06.2007","journal-title":"J Neurosci"},{"key":"3176_CR18","doi-asserted-by":"publisher","first-page":"105383","DOI":"10.1016\/j.neubiorev.2023.105383","volume":"153","author":"M de Leeuw","year":"2023","unstructured":"de Leeuw M, Verhoeve SI, van der Wee NJA et al (2023) The role of the circadian system in the etiology of depression. Neurosci Biobehav Rev 153:105383. https:\/\/doi.org\/10.1016\/j.neubiorev.2023.105383","journal-title":"Neurosci Biobehav Rev"},{"key":"3176_CR19","doi-asserted-by":"publisher","first-page":"3607","DOI":"10.1523\/jneurosci.3137-14.2015","volume":"35","author":"FH Do-Monte","year":"2015","unstructured":"Do-Monte FH, Manzano-Nieves G, Qui\u00f1ones-Laracuente K et al (2015) Revisiting the role of infralimbic cortex in fear extinction with optogenetics. J Neurosci 35:3607\u20133615. https:\/\/doi.org\/10.1523\/jneurosci.3137-14.2015","journal-title":"J Neurosci"},{"key":"3176_CR20","doi-asserted-by":"publisher","first-page":"3195","DOI":"10.1111\/j.1460-9568.2007.05581.x","volume":"25","author":"C Guilding","year":"2007","unstructured":"Guilding C, Piggins HD (2007) Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain? Eur J Neurosci 25:3195\u20133216. https:\/\/doi.org\/10.1111\/j.1460-9568.2007.05581.x","journal-title":"Eur J Neurosci"},{"key":"3176_CR21","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.neubiorev.2020.07.023","volume":"118","author":"MJ Hartsock","year":"2020","unstructured":"Hartsock MJ, Spencer RL (2020) Memory and the circadian system: identifying candidate mechanisms by which local clocks in the brain may regulate synaptic plasticity. Neurosci Biobehav Rev 118:134\u2013162. https:\/\/doi.org\/10.1016\/j.neubiorev.2020.07.023","journal-title":"Neurosci Biobehav Rev"},{"key":"3176_CR22","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1177\/07487304221128161","volume":"38","author":"MJ Hartsock","year":"2023","unstructured":"Hartsock MJ, Brennan NA, Spencer RL (2023) Circadian Rhythms in Fear Extinction Recall Depend on the Time of Day of Extinction Recall, Not the Time of Day of Extinction Learning. J Biol Rhythm 38:109\u2013115. https:\/\/doi.org\/10.1177\/07487304221128161","journal-title":"J Biol Rhythm"},{"issue":"39","key":"3176_CR23","doi-asserted-by":"publisher","first-page":"e0878242024","DOI":"10.1523\/jneurosci.0878-24.2024","volume":"44","author":"MJ Hartsock","year":"2024","unstructured":"Hartsock MJ, Levy CT, Navarro MJ et al (2024) Circadian rhythms in conditioned threat extinction reflect time-of-day differences in ventromedial prefrontal cortex neural processing. J Neurosci 44:e0878242024. https:\/\/doi.org\/10.1523\/jneurosci.0878-24.2024","journal-title":"J Neurosci"},{"key":"3176_CR24","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/nrn2699","volume":"10","author":"A Holtmaat","year":"2009","unstructured":"Holtmaat A, Svoboda K (2009) Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 10:647\u2013658. https:\/\/doi.org\/10.1038\/nrn2699","journal-title":"Nat Rev Neurosci"},{"key":"3176_CR25","doi-asserted-by":"publisher","first-page":"M13","DOI":"10.1530\/joe-15-0078","volume":"226","author":"M Ikeda","year":"2015","unstructured":"Ikeda M, Hojo Y, Komatsuzaki Y et al (2015) Hippocampal spine changes across the sleep-wake cycle: corticosterone and kinases. J Endocrinol 226:M13\u201327. https:\/\/doi.org\/10.1530\/joe-15-0078","journal-title":"J Endocrinol"},{"key":"3176_CR26","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1152\/physrev.00018.2015","volume":"96","author":"I Izquierdo","year":"2016","unstructured":"Izquierdo I, Furini CRG, Myskiw JC (2016) Fear Memory. Physiol Rev 96:695\u2013750. https:\/\/doi.org\/10.1152\/physrev.00018.2015","journal-title":"Physiol Rev"},{"key":"3176_CR27","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.1111\/ejn.13045","volume":"42","author":"M Jasinska","year":"2015","unstructured":"Jasinska M, Grzegorczyk A, Woznicka O et al (2015) Circadian rhythmicity of synapses in mouse somatosensory cortex. Eur J Neurosci 42:2585\u20132594. https:\/\/doi.org\/10.1111\/ejn.13045","journal-title":"Eur J Neurosci"},{"key":"3176_CR28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225394","volume":"14","author":"M Jasinska","year":"2019","unstructured":"Jasinska M, Jasek-Gajda E, Woznicka O et al (2019) Circadian clock regulates the shape and content of dendritic spines in mouse barrel cortex. PLoS One 14:e0225394. https:\/\/doi.org\/10.1371\/journal.pone.0225394","journal-title":"PLoS One"},{"key":"3176_CR29","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1073\/pnas.1018375108","volume":"108","author":"IN Karatsoreos","year":"2011","unstructured":"Karatsoreos IN, Bhagat S, Bloss EB et al (2011) Disruption of circadian clocks has ramifications for metabolism, brain, and behavior. Proc Natl Acad Sci USA 108:1657\u20131662. https:\/\/doi.org\/10.1073\/pnas.1018375108","journal-title":"Proc Natl Acad Sci USA"},{"key":"3176_CR30","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1038\/npp.2015.276","volume":"41","author":"H-S Kim","year":"2016","unstructured":"Kim H-S, Cho H-Y, Augustine GJ, Han J-H (2016) Selective Control of Fear Expression by Optogenetic Manipulation of Infralimbic Cortex after Extinction. Neuropsychopharmacology: official publication Am Coll Neuropsychopharmacol 41:1261\u20131273. https:\/\/doi.org\/10.1038\/npp.2015.276","journal-title":"Neuropsychopharmacology: official publication Am Coll Neuropsychopharmacol"},{"key":"3176_CR31","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0951","volume":"371","author":"KB Koronowski","year":"2021","unstructured":"Koronowski KB, Sassone-Corsi P (2021) Communicating clocks shape circadian homeostasis. Science 371:eabd0951. https:\/\/doi.org\/10.1126\/science.abd0951","journal-title":"Science"},{"key":"3176_CR32","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nature10792","volume":"483","author":"CSW Lai","year":"2012","unstructured":"Lai CSW, Franke TF, Gan W-B (2012) Opposite effects of fear conditioning and extinction on dendritic spine remodelling. Nature 483:87\u201391. https:\/\/doi.org\/10.1038\/nature10792","journal-title":"Nature"},{"key":"3176_CR33","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/nn.3387","volume":"16","author":"C Liston","year":"2013","unstructured":"Liston C, Cichon JM, Jeanneteau F et al (2013) Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance. Nat Neurosci 16:698\u2013705. https:\/\/doi.org\/10.1038\/nn.3387","journal-title":"Nat Neurosci"},{"key":"3176_CR34","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41593-018-0137-x","volume":"21","author":"R Marek","year":"2018","unstructured":"Marek R, Xu L, Sullivan RKP, Sah P (2018) Excitatory connections between the prelimbic and infralimbic medial prefrontal cortex show a role for the prelimbic cortex in fear extinction. Nat Neurosci 21:654\u2013658. https:\/\/doi.org\/10.1038\/s41593-018-0137-x","journal-title":"Nat Neurosci"},{"key":"3176_CR35","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00213-018-5033-2","volume":"236","author":"R Marek","year":"2019","unstructured":"Marek R, Sun Y, Sah P (2019) Neural circuits for a top-down control of fear and extinction. Psychopharmacology (Berl) 236:313\u2013320. https:\/\/doi.org\/10.1007\/s00213-018-5033-2","journal-title":"Psychopharmacology (Berl)"},{"key":"3176_CR36","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/nn.2934","volume":"14","author":"S Maret","year":"2011","unstructured":"Maret S, Faraguna U, Nelson AB et al (2011) Sleep and waking modulate spine turnover in the adolescent mouse cortex. Nat Neurosci 14:1418\u20131420. https:\/\/doi.org\/10.1038\/nn.2934","journal-title":"Nat Neurosci"},{"key":"3176_CR37","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.psyneuen.2016.09.008","volume":"74","author":"AE Meuret","year":"2016","unstructured":"Meuret AE, Rosenfield D, Bhaskara L et al (2016) Timing matters: Endogenous cortisol mediates benefits from early-day psychotherapy. Psychoneuroendocrinology 74:197\u2013202. https:\/\/doi.org\/10.1016\/j.psyneuen.2016.09.008","journal-title":"Psychoneuroendocrinology"},{"key":"3176_CR38","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev.psych.121208.131631","volume":"63","author":"MR Milad","year":"2012","unstructured":"Milad MR, Quirk GJ (2012) Fear extinction as a model for translational neuroscience: ten years of progress. Ann Rev Psychol 63:129\u2013151. https:\/\/doi.org\/10.1146\/annurev.psych.121208.131631","journal-title":"Ann Rev Psychol"},{"key":"3176_CR39","doi-asserted-by":"publisher","DOI":"10.1111\/jne.13212","volume":"34","author":"AM Miller","year":"2022","unstructured":"Miller AM, Daniels RM, Sheng JA et al (2022) Glucocorticoid regulation of diurnal spine plasticity in the murine ventromedial prefrontal cortex. J Neuroendocrinol 34:e13212. https:\/\/doi.org\/10.1111\/jne.13212","journal-title":"J Neuroendocrinol"},{"key":"3176_CR40","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ynstr.2015.12.002","volume":"3","author":"KM Moench","year":"2016","unstructured":"Moench KM, Maroun M, Kavushansky A, Wellman C (2016) Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress. Neurobiol stress 3:23\u201333. https:\/\/doi.org\/10.1016\/j.ynstr.2015.12.002","journal-title":"Neurobiol stress"},{"issue":"1","key":"3176_CR41","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s12915-022-01333-z","volume":"20","author":"RJ Nelson","year":"2022","unstructured":"Nelson RJ, Bumgarner JR, Liu JA et al (2022) Time of day as a critical variable in biology. BMC Biol 20:142. https:\/\/doi.org\/10.1186\/s12915-022-01333-z","journal-title":"BMC Biol"},{"key":"3176_CR42","unstructured":"NIH (2025) Sex as a biological variable. https:\/\/orwh.od.nih.gov\/sex-as-biological-variable"},{"key":"3176_CR43","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1146\/annurev.physiol.64.081501.160008","volume":"64","author":"EA Nimchinsky","year":"2002","unstructured":"Nimchinsky EA, Sabatini BL, Svoboda K (2002) STRUCTURE AND FUNCTION OF DENDRITIC SPINES. Annu Rev Physiol 64:313\u2013353. https:\/\/doi.org\/10.1146\/annurev.physiol.64.081501.160008","journal-title":"Annu Rev Physiol"},{"key":"3176_CR44","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1016\/j.jpsychires.2013.07.027","volume":"47","author":"EF Pace-Schott","year":"2013","unstructured":"Pace-Schott EF, Spencer RMC, Vijayakumar S et al (2013) Extinction of conditioned fear is better learned and recalled in the morning than in the evening. J Psychiatr Res 47:1776\u20131784. https:\/\/doi.org\/10.1016\/j.jpsychires.2013.07.027","journal-title":"J Psychiatr Res"},{"key":"3176_CR45","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"G Paxinos","year":"2007","unstructured":"Paxinos G, Watson C (2007) The Rat Brain in Stereotaxic Coordinates. Academic Press"},{"key":"3176_CR46","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.bbr.2009.07.021","volume":"205","author":"C Perez-Cruz","year":"2009","unstructured":"Perez-Cruz C, Simon M, Fl\u00fcgge G et al (2009) Diurnal rhythm and stress regulate dendritic architecture and spine density of pyramidal neurons in the rat infralimbic cortex. Behav Brain Res 205:406\u2013413. https:\/\/doi.org\/10.1016\/j.bbr.2009.07.021","journal-title":"Behav Brain Res"},{"key":"3176_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111229","volume":"40","author":"Q Qiao","year":"2022","unstructured":"Qiao Q, Wu C, Ma L et al (2022) Motor learning-induced new dendritic spines are preferentially involved in the learned task than existing spines. Cell Rep 40:111229. https:\/\/doi.org\/10.1016\/j.celrep.2022.111229","journal-title":"Cell Rep"},{"key":"3176_CR48","doi-asserted-by":"publisher","first-page":"5704","DOI":"10.1523\/jneurosci.0786-04.2004","volume":"24","author":"E Santini","year":"2004","unstructured":"Santini E, Ge H, Ren K et al (2004) Consolidation of fear extinction requires protein synthesis in the medial prefrontal cortex. J Neurosci 24:5704\u20135710. https:\/\/doi.org\/10.1523\/jneurosci.0786-04.2004","journal-title":"J Neurosci"},{"key":"3176_CR49","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.neuron.2013.11.006","volume":"81","author":"V Senn","year":"2014","unstructured":"Senn V, Wolff SBE, Herry C et al (2014) Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron 81:428\u2013437. https:\/\/doi.org\/10.1016\/j.neuron.2013.11.006","journal-title":"Neuron"},{"key":"3176_CR50","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1037\/a0035963","volume":"128","author":"BL Smarr","year":"2014","unstructured":"Smarr BL, Jennings KJ, Driscoll JR, Kriegsfeld LJ (2014) A time to remember: the role of circadian clocks in learning and memory. Behav Neurosci 128:283\u2013303. https:\/\/doi.org\/10.1037\/a0035963","journal-title":"Behav Neurosci"},{"key":"3176_CR51","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.neuron.2012.09.028","volume":"76","author":"F Sotres-Bayon","year":"2012","unstructured":"Sotres-Bayon F, Sierra-Mercado D, Pardilla-Delgado E, Quirk GJ (2012) Gating of fear in prelimbic cortex by hippocampal and amygdala inputs. Neuron 76:804\u2013812. https:\/\/doi.org\/10.1016\/j.neuron.2012.09.028","journal-title":"Neuron"},{"key":"3176_CR52","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.yfrne.2017.12.005","volume":"49","author":"RL Spencer","year":"2018","unstructured":"Spencer RL, Chun LE, Hartsock MJ, Woodruff ER (2018) Glucocorticoid hormones are both a major circadian signal and major stress signal: How this shared signal contributes to a dynamic relationship between the circadian and stress systems. Front Neuroendocr 49:52\u201371. https:\/\/doi.org\/10.1016\/j.yfrne.2017.12.005","journal-title":"Front Neuroendocr"},{"key":"3176_CR53","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0157-25.2025","author":"WJ Stritzel","year":"2025","unstructured":"Stritzel WJ, Levy C, Ravenel JR et al (2025) Red light sensitivity of non-image and image forming visual systems of laboratory rodents: circadian disruption and behavioral detection. J Neurosci. https:\/\/doi.org\/10.1523\/jneurosci.0157-25.2025","journal-title":"J Neurosci"},{"key":"3176_CR54","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nrn3945","volume":"16","author":"P Tovote","year":"2015","unstructured":"Tovote P, Fadok JP, L\u00fcthi A (2015) Neuronal circuits for fear and anxiety. Nat Rev Neurosci 16:317\u2013331. https:\/\/doi.org\/10.1038\/nrn3945","journal-title":"Nat Rev Neurosci"},{"key":"3176_CR55","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1101\/lm.306106","volume":"13","author":"I Vidal-Gonzalez","year":"2006","unstructured":"Vidal-Gonzalez I, Vidal-Gonzalez B, Rauch SL, Quirk GJ (2006) Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learn Mem 13:728\u2013733. https:\/\/doi.org\/10.1101\/lm.306106","journal-title":"Learn Mem"},{"key":"3176_CR56","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.bbr.2015.03.006","volume":"286","author":"ER Woodruff","year":"2015","unstructured":"Woodruff ER, Greenwood BN, Chun LE et al (2015) Adrenal-dependent diurnal modulation of conditioned fear extinction learning. Behav Brain Res 286:249\u2013255. https:\/\/doi.org\/10.1016\/j.bbr.2015.03.006","journal-title":"Behav Brain Res"},{"key":"3176_CR57","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1210\/en.2015-1884","volume":"157","author":"ER Woodruff","year":"2016","unstructured":"Woodruff ER, Chun LE, Hinds LR, Spencer RL (2016) Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex. Endocrinology 157:1522\u20131534. https:\/\/doi.org\/10.1210\/en.2015-1884","journal-title":"Endocrinology"},{"issue":"6","key":"3176_CR58","doi-asserted-by":"publisher","first-page":"ENEURO.0455-18.","DOI":"10.1523\/eneuro.0455-18.2018","volume":"5","author":"ER Woodruff","year":"2018","unstructured":"Woodruff ER, Chun LE, Hinds LR et al (2018) Coordination between prefrontal cortex clock gene expression and corticosterone contributes to enhanced conditioned fear extinction recall. eNeuro 5:ENEURO.0455-18.2018. https:\/\/doi.org\/10.1523\/eneuro.0455-18.2018","journal-title":"eNeuro"},{"key":"3176_CR59","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.jpsychires.2021.01.034","volume":"135","author":"C Wurst","year":"2021","unstructured":"Wurst C, Schiele MA, Stonawski S et al (2021) Impaired fear learning and extinction, but not generalization, in anxious and non-anxious depression. J Psychiatr Res 135:294\u2013301. https:\/\/doi.org\/10.1016\/j.jpsychires.2021.01.034","journal-title":"J Psychiatr Res"},{"key":"3176_CR60","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1146\/annurev.neuro.24.1.1071","volume":"24","author":"R Yuste","year":"2001","unstructured":"Yuste R, Bonhoeffer T (2001) Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 24:1071\u20131089. https:\/\/doi.org\/10.1146\/annurev.neuro.24.1.1071","journal-title":"Annu Rev Neurosci"},{"key":"3176_CR61","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1002\/da.22463","volume":"33","author":"DV Zuj","year":"2016","unstructured":"Zuj DV, Palmer MA, Hsu C-MK, IMPAIRED FEAR EXTINCTION ASSOCIATED WITH PTSD INCREASES WITH HOURS-SINCE-WAKING (2016) Depress Anxiety 33:203\u2013210. https:\/\/doi.org\/10.1002\/da.22463","journal-title":"Depress Anxiety"},{"key":"3176_CR62","unstructured":"R Core Team (2025). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, Austria https:\/\/www.R-project.org\/"}],"container-title":["Brain Structure and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00429-026-03176-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00429-026-03176-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00429-026-03176-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:24:11Z","timestamp":1789806251000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00429-026-03176-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":62,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,11]]}},"alternative-id":["3176"],"URL":"https:\/\/doi.org\/10.1007\/s00429-026-03176-8","relation":{},"ISSN":["1863-2661"],"issn-type":[{"value":"1863-2661","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]},"assertion":[{"value":"16 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal use complied with guidelines of the Office of Laboratory Animal Welfare and in accordance with a project specific protocol approved by the IACUC at the University of Colorado Boulder.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"136"}}