{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T08:18:56Z","timestamp":1777105136107,"version":"3.51.4"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Syst. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The extinction of fear memories is an important component in regulating defensive behaviors, contributing toward adaptive processes essential for survival. The cerebellar medial nucleus (MCN) has bidirectional connections with the ventrolateral periaqueductal gray (vlPAG) and is implicated in the regulation of multiple aspects of fear, such as conditioned fear learning and the expression of defensive motor outputs. However, it is unclear how communication between the MCN and vlPAG changes during conditioned fear extinction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We use dynamic causal models (DCMs) to infer effective connectivity between the MCN and vlPAG during auditory cue-conditioned fear retrieval and extinction in the rat. DCMs determine causal relationships between neuronal sources by using neurobiologically motivated models to reproduce the dynamics of post-synaptic potentials generated by synaptic connections within and between brain regions. Auditory event related potentials (ERPs) during the conditioned tone offset were recorded simultaneously from MCN and vlPAG and then modeled to identify changes in the strength of the synaptic inputs between these brain areas and the relationship to freezing behavior across extinction trials. The DCMs were structured to model evoked responses to best represent conditioned tone offset ERPs and were adapted to represent PAG and cerebellar circuitry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With the use of Parametric Empirical Bayesian (PEB) analysis we found that the strength of the information flow, mediated through enhanced synaptic efficacy from MCN to vlPAG was inversely related to freezing during extinction, i.e., communication from MCN to vlPAG increased with extinction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results are consistent with the cerebellum contributing to predictive processes that underpin fear extinction.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnsys.2023.1148604","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T05:22:31Z","timestamp":1684300951000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dynamic causal modeling reveals increased cerebellar- periaqueductal gray communication during fear extinction"],"prefix":"10.3389","volume":"17","author":[{"given":"Elena","family":"Paci","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bridget M.","family":"Lumb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Apps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte L.","family":"Lawrenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalyn J.","family":"Moran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/nrn4028","article-title":"Neuronal circuits for fear and anxiety \u2014 the missing link.","volume":"16","author":"Apps","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1192\/s0007125000291897","article-title":"Cognitive brain potentials and their application.","volume":"157","author":"Blackwood","year":"1990","journal-title":"Br. J. Psychiatry"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1007\/s00429-019-01893-x","article-title":"Mapping the structural connectivity between the periaqueductal gray and the cerebellum in humans.","volume":"224","author":"Cacciola","year":"2019","journal-title":"Brain Struct. Funct."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1016\/j.neuroimage.2003.07.015","article-title":"A neural mass model for MEG\/EEG: coupling and neuronal dynamics","volume":"20","author":"David","year":"2003","journal-title":"Neuroimage"},{"key":"B5","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/j.neuroimage.2004.12.030","article-title":"Modelling event-related responses in the brain","volume":"25","author":"David","year":"2005","journal-title":"Neuroimage"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/j.neuroimage.2005.10.045","article-title":"Dynamic causal modeling of evoked responses in EEG and MEG","volume":"30","author":"David","year":"2006","journal-title":"Neuroimage"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46831","article-title":"The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm.","volume":"8","author":"Ernst","year":"2019","journal-title":"ELife"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1523\/JNEUROSCI.3361-15.2016","article-title":"Amygdala modulation of cerebellar learning.","volume":"36","author":"Farley","year":"2016","journal-title":"J. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/S1053-8119(03)00202-7","article-title":"Dynamic causal modelling.","volume":"19","author":"Friston","year":"2003","journal-title":"Neuroimage"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-18953-0","article-title":"Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey.","volume":"11","author":"Frontera","year":"2020","journal-title":"Nat. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/s41593-018-0174-5","article-title":"Dorsal tegmental dopamine neurons gate associative learning of fear.","volume":"21","author":"Groessl","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B12","author":"It\u014d","year":"1984","journal-title":"The cerebellum and neural control."},{"key":"B13","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.pneurobio.2006.02.006","article-title":"Cerebellar circuitry as a neuronal machine.","volume":"78","author":"Ito","year":"2006","journal-title":"Prog. Neurobiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/BF00199471","article-title":"Electroencephalogram and visual evoked potential generation in a mathematical model of coupled cortical columns","volume":"73","author":"Jansen","year":"1995","journal-title":"Biol. Cybern"},{"key":"B15","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nn.2594","article-title":"Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray.","volume":"13","author":"Johansen","year":"2010","journal-title":"Nat. Neurosci."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1101\/2022.02.07.479043","article-title":"Novel cerebello-amygdala connections provide missing link between cerebellum and limbic system.","author":"Jung","year":"2022","journal-title":"bioRxiv"},{"key":"B17","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.neuroimage.2007.02.046","article-title":"Dynamic causal modelling of evoked responses: the role of intrinsic connections","volume":"36","author":"Kiebel","year":"2007","journal-title":"Neuroimage"},{"key":"B18","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s11571-008-9038-0","article-title":"Dynamic causal modelling for EEG and MEG.","volume":"2","author":"Kiebel","year":"2008","journal-title":"Cogn. Neurodyn."},{"key":"B19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.nlm.2015.10.010","article-title":"Increased tone-offset response in the lateral nucleus of the amygdala underlies trace fear conditioning.","volume":"126","author":"Kim","year":"2015","journal-title":"Neurobiol. Learn. Mem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1113\/jphysiol.2013.268714","article-title":"Neural substrates underlying fear-evoked freezing: the periaqueductal grey-cerebellar link.","volume":"592","author":"Koutsikou","year":"2014","journal-title":"J. Physiol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7554\/ELIFE.76278","article-title":"Cerebellar modulation of memory encoding in the periaqueductal grey and fear behaviour.","volume":"11","author":"Lawrenson","year":"2022","journal-title":"ELife"},{"key":"B22","doi-asserted-by":"publisher","first-page":"872.e7","DOI":"10.1016\/j.celrep.2019.03.069","article-title":"Parallel processing of sound dynamics across mouse auditory cortex via spatially patterned thalamic inputs and distinct areal intracortical circuits.","volume":"27","author":"Liu","year":"2019","journal-title":"Cell Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1037\/0097-7403.32.2.164","article-title":"A short intertrial interval facilitates acquisition of context-conditioned fear and a short retention interval facilitates its expression.","volume":"32","author":"McNally","year":"2006","journal-title":"J. Exp. Psychol. Anim. Behav. Process"},{"key":"B24","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1111\/j.1749-6632.1997.tb48315.x","article-title":"Evidence for diminished P3 amplitudes in PTSD.","volume":"821","author":"Metzger","year":"1997","journal-title":"Ann. N Y Acad. Sci."},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2013.00057","article-title":"Neural masses and fields in dynamic causal modeling.","volume":"7","author":"Moran","year":"2013","journal-title":"Front. Comput. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"8227","DOI":"10.1523\/JNEUROSCI.4255-12.2013","article-title":"Free energy, precision and learning: the role of cholinergic neuromodulation.","volume":"33","author":"Moran","year":"2013","journal-title":"J. Neurosci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/j.neuroimage.2007.05.032","article-title":"A neural mass model of spectral responses in electrophysiology.","volume":"37","author":"Moran","year":"2007","journal-title":"Neuroimage"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1016\/S0006-3223(99)00047-5","article-title":"Sensory gating in chronic posttraumatic stress disorder: reduced auditory p50 suppression in combat veterans.","volume":"46","author":"Neylan","year":"1999","journal-title":"Biol. Psychiatry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/nn.4439","article-title":"A feedback neural circuit for calibrating aversive memory strength.","volume":"20","author":"Ozawa","year":"2017","journal-title":"Nat. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"9281","DOI":"10.1073\/pnas.160266497","article-title":"Learning about pain: the neural substrate of the prediction error for aversive events.","volume":"97","author":"Ploghaus","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B31","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/S0896-6273(00)80375-X","article-title":"Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala.","volume":"19","author":"Quirk","year":"1997","journal-title":"Neuron"},{"key":"B32","doi-asserted-by":"publisher","first-page":"8406","DOI":"10.1073\/pnas.112660399","article-title":"Cerebellar role in fear-conditioning consolidation.","volume":"99","author":"Sacchetti","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"B33","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1177\/1073858405276428","article-title":"The cerebellum: synaptic changes and fear conditioning.","volume":"11","author":"Sacchetti","year":"2005","journal-title":"Neuroscientist"},{"key":"B34","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/(SICI)1520-6394(1999)9:3<122::AID-DA4>3.0.CO;2-M","article-title":"Reduced sensory gating of the P1 potential in rape victims and combat veterans with posttraumatic stress disorder.","volume":"9","author":"Skinner","year":"1999","journal-title":"Depress. Anxiety"},{"key":"B35","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/0014-4886(76)90150-3","article-title":"Cerebellar pathways to ventral midbrain and nigra.","volume":"53","author":"Snider","year":"1976","journal-title":"Exp. Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/j.neuroimage.2009.03.025","article-title":"Bayesian model selection for group studies.","volume":"46","author":"Stephan","year":"2009","journal-title":"NeuroImage"},{"key":"B37","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.cortex.2009.11.008","article-title":"Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing.","volume":"46","author":"Stoodley","year":"2010","journal-title":"Cortex"},{"key":"B38","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/B978-0-444-63956-1.00004-7","article-title":"Functional topography of the human cerebellum.","volume":"154","author":"Stoodley","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0006-8993(90)90303-S","article-title":"Cerebellar vermis: essential for classically conditioned bradycardia in the rat.","volume":"509","author":"Supple","year":"1990","journal-title":"Brain Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/0031-9384(87)90156-9","article-title":"Effects of cerebellar vermal lesions on species-specific fear responses, neophobia, and taste-aversion learning in rats.","volume":"39","author":"Supple","year":"1987","journal-title":"Physiol. Behav."},{"key":"B41","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S0079-6123(00)24014-4","article-title":"Topography of cerebellar nuclear projections to the brain stem in the rat.","volume":"124","author":"Teune","year":"2000","journal-title":"Prog. Brain Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/nature17996","article-title":"Midbrain circuits for defensive behaviour.","volume":"534","author":"Tovote","year":"2016","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/J.NEULET.2015.07.026","article-title":"Cerebellar vermis contributes to the extinction of conditioned fear.","volume":"604","author":"Utz","year":"2015","journal-title":"Neurosci. Lett."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54302","article-title":"Cerebellar modulation of synaptic input to freezing-related neurons in the periaqueductal gray.","volume":"9","author":"Vaaga","year":"2020","journal-title":"ELife"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4109","DOI":"10.1097\/00001756-200112210-00049","article-title":"Defensive freezing evoked by electrical stimulation of the periaqueductal gray: comparison between dorsolateral and ventrolateral regions.","volume":"12","author":"Vianna","year":"2001","journal-title":"Neuroreport"},{"key":"B46","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/S0306-4522(02)00744-3","article-title":"Role of ventrolateral periaqueductal gray neurons in the behavioral and cardiovascular responses to contextual conditioned fear and poststress recovery.","volume":"116","author":"Walker","year":"2003","journal-title":"Neuroscience"},{"key":"B47","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1111\/ejn.14536","article-title":"The ventrolateral periaqueductal grey updates fear via positive prediction error.","volume":"51","author":"Walker","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"12707","DOI":"10.1523\/JNEUROSCI.1100-16.2016","article-title":"Neural correlates of fear in the periaqueductal gray.","volume":"36","author":"Watson","year":"2016","journal-title":"J. Neurosci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/S1364-6613(98)01221-2","article-title":"Internal models in the cerebellum.","volume":"2","author":"Wolpert","year":"1998","journal-title":"Trends Cogn. Sci."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.45013","article-title":"Ventrolateral periaqueductal gray neurons prioritize threat probability over fear output.","volume":"8","author":"Wright","year":"2019","journal-title":"ELife"},{"key":"B51","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neuroimage.2019.06.032","article-title":"A guide to group effective connectivity analysis, part 2: second level analysis with PEB.","volume":"200","author":"Zeidman","year":"2019","journal-title":"Neuroimage"}],"container-title":["Frontiers in Systems Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnsys.2023.1148604\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T05:22:36Z","timestamp":1684300956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnsys.2023.1148604\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":51,"alternative-id":["10.3389\/fnsys.2023.1148604"],"URL":"https:\/\/doi.org\/10.3389\/fnsys.2023.1148604","relation":{},"ISSN":["1662-5137"],"issn-type":[{"value":"1662-5137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,17]]},"article-number":"1148604"}}