{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:21:29Z","timestamp":1787570489551,"version":"build-2736575974"},"reference-count":114,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["671251"],"award-info":[{"award-number":["671251"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["FCT-PTDC\/MED-NEU\/28830\/2017"],"award-info":[{"award-number":["FCT-PTDC\/MED-NEU\/28830\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["SFRH\/BD\/132172\/2017"],"award-info":[{"award-number":["SFRH\/BD\/132172\/2017"]}]},{"DOI":"10.13039\/501100014069","name":"Champalimaud Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,28]]},"abstract":"<jats:p>The ability to persist toward a desired objective is a fundamental aspect of behavioral control whose impairment is implicated in several behavioral disorders. One of the prominent features of behavioral persistence is that its maturation occurs relatively late in development. This is presumed to echo the developmental time course of a corresponding circuit within late-maturing parts of the brain, such as the prefrontal cortex, but the specific identity of the responsible circuits is unknown. Here, we used a genetic approach to describe the maturation of the projection from layer 5 neurons of the neocortex to the dorsal raphe nucleus in mice. Using optogenetic-assisted circuit mapping, we show that this projection undergoes a dramatic increase in synaptic potency between postnatal weeks 3 and 8, corresponding to the transition from juvenile to adult. We then show that this period corresponds to an increase in the behavioral persistence that mice exhibit in a foraging task. Finally, we used a genetic targeting strategy that primarily affected neurons in the medial prefrontal cortex, to selectively ablate this pathway in adulthood and show that mice revert to a behavioral phenotype similar to juveniles. These results suggest that frontal cortical to dorsal raphe input is a critical anatomical and functional substrate of the development and manifestation of behavioral persistence.<\/jats:p>","DOI":"10.7554\/elife.93485","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T08:10:05Z","timestamp":1710317405000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.93485","source":"Crossref","is-referenced-by-count":5,"title":["Maturation of cortical input to dorsal raphe nucleus increases behavioral persistence in mice"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8442-4243","authenticated-orcid":true,"given":"Nicolas","family":"Gutierrez-Castellanos","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03g001n57","id-type":"ROR","asserted-by":"publisher"}],"name":"Champalimaud Research, Champalimaud Foundation","place":["Lisbon, Portugal"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6800-8071","authenticated-orcid":true,"given":"Dario","family":"Sarra","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03g001n57","id-type":"ROR","asserted-by":"publisher"}],"name":"Champalimaud Research, Champalimaud Foundation","place":["Lisbon, Portugal"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Nuffield Department of Clinical Neurosciences, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Beatriz S","family":"Godinho","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03g001n57","id-type":"ROR","asserted-by":"publisher"}],"name":"Champalimaud Research, Champalimaud Foundation","place":["Lisbon, Portugal"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Nuffield Department of Clinical Neurosciences, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7913-9109","authenticated-orcid":true,"given":"Zachary F","family":"Mainen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03g001n57","id-type":"ROR","asserted-by":"publisher"}],"name":"Champalimaud Research, Champalimaud Foundation","place":["Lisbon, Portugal"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/nrn3465","type":"journal-article","article-title":"Imaging structural co-variance between human brain regions","volume":"14","author":"Alexander-Bloch","year":"2013","journal-title":"Nature Reviews. Neuroscience"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"2976","DOI":"10.1523\/JNEUROSCI.3097-16.2017","type":"journal-article","article-title":"Optogenetic examination of prefrontal-amygdala synaptic development","volume":"37","author":"Arruda-Carvalho","year":"2017","journal-title":"The Journal of Neuroscience"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00063","type":"journal-article","article-title":"Excitotoxic lesions of the infralimbic, but not prelimbic cortex facilitate reversal of appetitive discriminative context conditioning: the role of the infralimbic cortex in context generalization","volume":"8","author":"Ashwell","year":"2014","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/j.neuron.2019.06.001","type":"journal-article","article-title":"Stable representations of decision variables for flexible behavior","volume":"103","author":"Bari","year":"2019","journal-title":"Neuron"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo","type":"software","article-title":"Juliastats\/Mixedmodels","volume-title":"Zenodo","author":"Bates","year":"2021","unstructured":"Bates D, Alday P, Kleinschmidt D, Calder\u00f3n JBS, Zhan L, Noack A, Arslan A, Bouchet-Valat M, Kelman T, Baldassari A, Ehinger B, Karrasch D, Saba E, Quinn J, Hatherly M, Piibeleht M, Mogensen PK, Babayan S, Gagnon YL. 2021. Juliastats\/Mixedmodels. Zenodo. v3.8.0. https:\/\/doi.org\/10.5281\/zenodo."},{"key":"bib6","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1210\/en.2018-00220","type":"journal-article","article-title":"Comparing postnatal development of gonadal hormones and associated social behaviors in rats, mice, and humans","volume":"159","author":"Bell","year":"2018","journal-title":"Endocrinology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1093\/brain\/awh135","type":"journal-article","article-title":"Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions","volume":"127","author":"Berlin","year":"2004","journal-title":"Brain"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1137\/141000671","type":"journal-article","article-title":"Julia: A fresh approach to numerical computing","volume":"59","author":"Bezanson","year":"2017","journal-title":"SIAM Review"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1016\/j.neuron.2021.02.011","type":"journal-article","article-title":"A transient developmental increase in prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice","volume":"109","author":"Bitzenhofer","year":"2021","journal-title":"Neuron"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"4773","DOI":"10.1523\/JNEUROSCI.0414-20.2020","type":"journal-article","article-title":"Prelimbic and infralimbic prefrontal regulation of active and inhibitory avoidance and reward-seeking","volume":"40","author":"Capuzzo","year":"2020","journal-title":"The Journal of Neuroscience"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"14998","DOI":"10.1073\/pnas.1108561108","type":"journal-article","article-title":"Behavioral and neural correlates of delay of gratification 40 years later","volume":"108","author":"Casey","year":"2011","journal-title":"PNAS"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"9917","DOI":"10.1523\/JNEUROSCI.21-24-09917.2001","type":"journal-article","article-title":"Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: Involvement of serotonin-1A, GABA(A), and glutamate receptors","volume":"21","author":"Celada","year":"2001","journal-title":"The Journal of Neuroscience"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00043","type":"journal-article","article-title":"Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat","volume":"8","author":"Challis","year":"2014","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"bib14","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1021\/acschemneuro.5b00007","type":"journal-article","article-title":"Top-Down Control of Serotonin Systems by the Prefrontal Cortex: A Path toward Restored Socioemotional Function in Depression","volume":"6","author":"Challis","year":"2015","journal-title":"ACS Chem. Neurosci"},{"key":"bib15","doi-asserted-by":"crossref","DOI":"10.1016\/0040-5809(76)90040-X","type":"journal-article","article-title":"Optimal foraging, the marginal value theorem","volume":"9","author":"Charnov","year":"1976","journal-title":"Theor. Popul. Biol"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2018.00516","type":"journal-article","article-title":"Increased inhibition of the amygdala by the mpfc may reflect a resilience factor in post-traumatic stress disorder: a resting-state fmri granger causality analysis","volume":"9","author":"Chen","year":"2018","journal-title":"Frontiers in Psychiatry"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.tins.2020.10.017","type":"journal-article","article-title":"Prefrontal cortex development in health and disease: Lessons from rodents and humans","volume":"44","author":"Chini","year":"2021","journal-title":"Trends in Neurosciences"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67387","type":"journal-article","article-title":"The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice","volume":"10","author":"Ciaramelli","year":"2021","journal-title":"eLife"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.tics.2007.10.011","type":"journal-article","article-title":"Serotoninergic regulation of emotional and behavioural control processes","volume":"12","author":"Cools","year":"2008","journal-title":"Trends in Cognitive Sciences"},{"key":"bib20","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.neuron.2015.03.040","type":"journal-article","article-title":"A Corticothalamic Switch: Controlling the Thalamus with Dynamic Synapses","volume":"86","author":"Crandall","year":"2015","journal-title":"Neuron"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/nrn.2017.8","type":"journal-article","article-title":"Fractionating impulsivity: neuropsychiatric implications","volume":"18","author":"Dalley","year":"2017","journal-title":"Nature Reviews Neuroscience"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1146\/annurev.neuro.051508.135607","type":"journal-article","article-title":"Serotonin in affective control","volume":"32","author":"Dayan","year":"2009","journal-title":"Annual Review of Neuroscience"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1113\/jphysiol.2006.115311","type":"journal-article","article-title":"NMDA receptors trigger neurosecretion of 5-HT within dorsal raphe nucleus of the rat in the absence of action potential firing","volume":"577","author":"de Kock","year":"2006","journal-title":"The Journal of Physiology"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7395","type":"journal-article","article-title":"FAAH genetic variation enhances fronto-amygdala function in mouse and human","volume":"6","author":"Dincheva","year":"2015","journal-title":"Nature Communications"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1037\/a0029697","type":"journal-article","article-title":"Age-related differences in impulsivity among adolescent and adult Sprague-Dawley rats","volume":"126","author":"Doremus-Fitzwater","year":"2012","journal-title":"Behavioral Neuroscience"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1016\/j.neuropsychologia.2005.10.010","type":"journal-article","article-title":"What have we learned about cognitive development from neuroimaging?","volume":"44","author":"Durston","year":"2006","journal-title":"Neuropsychologia"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000381","type":"journal-article","article-title":"Functional brain networks develop from a \u201clocal to distributed\u201d organization","volume":"5","author":"Fair","year":"2009","journal-title":"PLOS Computational Biology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1093\/brain\/awl017","type":"journal-article","article-title":"Deciding how to decide: ventromedial frontal lobe damage affects information acquisition in multi-attribute decision making","volume":"129","author":"Fellows","year":"2006","journal-title":"Brain"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2014.01027","type":"journal-article","article-title":"Development of thalamocortical connections between the mediodorsal thalamus and the prefrontal cortex and its implication in cognition","volume":"8","author":"Ferguson","year":"2014","journal-title":"Frontiers in Human Neuroscience"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.cub.2014.12.002","type":"journal-article","article-title":"Activation of dorsal raphe serotonergic neurons promotes waiting but is not reinforcing","volume":"25","author":"Fonseca","year":"2015","journal-title":"Current Biology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"5429","DOI":"10.1073\/pnas.1522754113","type":"journal-article","article-title":"Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids","volume":"113","author":"Geddes","year":"2016","journal-title":"PNAS"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"4500","DOI":"10.1073\/pnas.1600013113","type":"journal-article","article-title":"Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species","volume":"113","author":"Gee","year":"2016","journal-title":"PNAS"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1016\/j.neuron.2013.10.016","type":"journal-article","article-title":"GENSAT BAC cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits","volume":"80","author":"Gerfen","year":"2013","journal-title":"Neuron"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2015.00298","type":"journal-article","article-title":"The role of the medial prefrontal cortex in the conditioning and extinction of fear","volume":"9","author":"Giustino","year":"2015","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/S0306-4522(96)00380-6","type":"journal-article","article-title":"The course of neural projection from the prefrontal cortex to the nucleus accumbens in the rat","volume":"76","author":"Gorelova","year":"1996","journal-title":"Neuroscience"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2020.00051","type":"journal-article","article-title":"A critical period for prefrontal network configurations underlying psychiatric disorders and addiction","volume":"14","author":"Guirado","year":"2020","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordhb\/9780195389715.013.0082","type":"book-chapter","article-title":"Development of impulse control, inhibition, and self-regulatory behaviors in normative populations across the LifeSpan","volume-title":"The Oxford Handbook of Impulse Control Disorders","author":"Hammond","year":"2011"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1177\/2398212818772962","type":"journal-article","article-title":"Effects of anterior cingulate cortex lesions on a continuous performance task for mice","volume":"2","author":"Hvoslef-Eide","year":"2018","journal-title":"Brain and Neuroscience Advances"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"15535","DOI":"10.1523\/JNEUROSCI.2825-10.2010","type":"journal-article","article-title":"Strengthening of top-down frontal cognitive control networks underlying the development of inhibitory control: A functional magnetic resonance imaging effective connectivity study","volume":"30","author":"Hwang","year":"2010","journal-title":"The Journal of Neuroscience"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1097\/00001756-200212200-00016","type":"journal-article","article-title":"Orbitofrontal cortex dysfunction in attention-deficit hyperactivity disorder revealed by reversal and extinction tasks","volume":"13","author":"Itami","year":"2002","journal-title":"Neuroreport"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neuroscience.2016.03.021","type":"journal-article","article-title":"The neural basis of reversal learning: An updated perspective","volume":"345","author":"Izquierdo","year":"2017","journal-title":"Neuroscience"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126956","type":"journal-article","article-title":"Sodium salicylate suppresses gabaergic inhibitory activity in neurons of rodent dorsal raphe nucleus","volume":"10","author":"Jin","year":"2015","journal-title":"PLOS ONE"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.dcn.2011.05.008","type":"journal-article","article-title":"Juvenile mice show greater flexibility in multiple choice reversal learning than adults","volume":"1","author":"Johnson","year":"2011","journal-title":"Developmental Cognitive Neuroscience"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.64567","type":"journal-article","article-title":"Linking mPFC circuit maturation to the developmental regulation of emotional memory and cognitive flexibility","volume":"10","author":"Klune","year":"2021","journal-title":"eLife"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41386-021-01137-9","type":"journal-article","article-title":"Development of prefrontal cortex","volume":"47","author":"Kolk","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1152\/jn.00189.2017","type":"journal-article","article-title":"Prefrontal cortical-specific differences in behavior and synaptic plasticity between adolescent and adult mice","volume":"119","author":"Konstantoudaki","year":"2018","journal-title":"Journal of Neurophysiology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.neubiorev.2018.09.005","type":"journal-article","article-title":"Adolescence as a neurobiological critical period for the development of higher-order cognition","volume":"94","author":"Larsen","year":"2018","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S0149-7634(03)00006-X","type":"journal-article","article-title":"Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence","volume":"27","author":"Laviola","year":"2003","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"3406","DOI":"10.1093\/cercor\/bhu156","type":"journal-article","article-title":"Satb2 regulates the differentiation of both callosal and subcerebral projection neurons in the developing cerebral cortex","volume":"25","author":"Leone","year":"2015","journal-title":"Cerebral Cortex"},{"key":"bib50","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2018.00084","type":"journal-article","article-title":"Cell-type-specific afferent innervation of the nucleus accumbens core and shell","volume":"12","author":"Li","year":"2018","journal-title":"Frontiers in Neuroanatomy"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"17278","DOI":"10.1073\/pnas.2000523117","type":"journal-article","article-title":"Inhibition of impulsive action by projection-defined prefrontal pyramidal neurons","volume":"117","author":"Li","year":"2020","journal-title":"PNAS"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1111\/j.1460-9568.2005.03930.x","type":"journal-article","article-title":"Somatodendritic autoreceptor regulation of serotonergic neurons: dependence on L-tryptophan and tryptophan hydroxylase-activating kinases","volume":"21","author":"Liu","year":"2005","journal-title":"The European Journal of Neuroscience"},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03438-y","type":"journal-article","article-title":"Activation of serotonin neurons promotes active persistence in a probabilistic foraging task","volume":"9","author":"Lottem","year":"2018","journal-title":"Nature Communications"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1006\/nimg.2000.0743","type":"journal-article","article-title":"Maturation of widely distributed brain function subserves cognitive development","volume":"13","author":"Luna","year":"2001","journal-title":"NeuroImage"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1146\/annurev-neuro-071714-034054","type":"journal-article","article-title":"An integrative model of the maturation of cognitive control","volume":"38","author":"Luna","year":"2015","journal-title":"Annual Review of Neuroscience"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ynstr.2014.09.003","type":"journal-article","article-title":"Behavioral control blunts reactions to contemporaneous and future adverse events: medial prefrontal cortex plasticity and a corticostriatal network","volume":"1","author":"Maier","year":"2015","journal-title":"Neurobiology of Stress"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1126\/science.2658056","type":"journal-article","article-title":"Delay of gratification in children","volume":"244","author":"Mischel","year":"1989","journal-title":"Science"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/j.1460-9568.2010.07480.x","type":"journal-article","article-title":"Activation of the central serotonergic system in response to delayed but not omitted rewards","volume":"33","author":"Miyazaki","year":"2011","journal-title":"The European Journal of Neuroscience"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"10451","DOI":"10.1523\/JNEUROSCI.0915-12.2012","type":"journal-article","article-title":"Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed rewards","volume":"32","author":"Miyazaki","year":"2012","journal-title":"Journal of Neuroscience"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1016\/j.cub.2014.07.041","type":"journal-article","article-title":"Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards","volume":"24","author":"Miyazaki","year":"2014","journal-title":"Current Biology"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04496-y","type":"journal-article","article-title":"Reward probability and timing uncertainty alter the effect of dorsal raphe serotonin neurons on patience","volume":"9","author":"Miyazaki","year":"2018","journal-title":"Nature Communications"},{"key":"bib62","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc7246","type":"journal-article","article-title":"Serotonergic projections to the orbitofrontal and medial prefrontal cortices differentially modulate waiting for future rewards","volume":"6","author":"Miyazaki","year":"2020","journal-title":"Science Advances"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1073\/pnas.1010076108","type":"journal-article","article-title":"A gradient of childhood self-control predicts health, wealth, and public safety","volume":"108","author":"Moffitt","year":"2011","journal-title":"PNAS"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1890\/0012-9658(2000)081[2061:OFMMPU]2.0.CO;2","type":"journal-article","article-title":"Optimally foraging mice match patch use with habitat differences in fitness","volume":"81","author":"Morris","year":"2000","journal-title":"Ecology"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1093\/cercor\/6.3.470","type":"journal-article","article-title":"The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task","volume":"6","author":"Muir","year":"1996","journal-title":"Cerebral Cortex"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.neuron.2017.04.040","type":"journal-article","article-title":"Distinct sources of deterministic and stochastic components of action timing decisions in rodent frontal cortex","volume":"94","author":"Murakami","year":"2017","journal-title":"Neuron"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1162\/0898929041920441","type":"journal-article","article-title":"Maturation of white matter is associated with the development of cognitive functions during childhood","volume":"16","author":"Nagy","year":"2004","journal-title":"Journal of Cognitive Neuroscience"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"4490","DOI":"10.1523\/JNEUROSCI.3537-17.2018","type":"journal-article","article-title":"Cell-type-specific contributions of medial prefrontal neurons to flexible behaviors","volume":"38","author":"Nakayama","year":"2018","journal-title":"The Journal of Neuroscience"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/j.neuroscience.2005.11.072","type":"journal-article","article-title":"Reversible inactivations of rat medial prefrontal cortex impair the ability to wait for a stimulus","volume":"139","author":"Narayanan","year":"2006","journal-title":"Neuroscience"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1038\/nn.3549","type":"journal-article","article-title":"Common medial frontal mechanisms of adaptive control in humans and rodents","volume":"16","author":"Narayanan","year":"2013","journal-title":"Nature Neuroscience"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/s41386-018-0254-y","type":"journal-article","article-title":"Manipulation of dorsal raphe serotonergic neurons modulates active coping to inescapable stress and anxiety-related behaviors in mice and rats","volume":"44","author":"Nishitani","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"bib72","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107703","type":"journal-article","article-title":"Different roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects","volume":"167","author":"Ohmura","year":"2020","journal-title":"Neuropharmacology"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1038\/nn.4260","type":"journal-article","article-title":"Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-\/-) mice","volume":"19","author":"Peixoto","year":"2016","journal-title":"Nature Neuroscience"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nature07709","type":"journal-article","article-title":"The subcellular organization of neocortical excitatory connections","volume":"457","author":"Petreanu","year":"2009","journal-title":"Nature"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0306-4522(85)90002-8","type":"journal-article","article-title":"The topographic order of inputs to nucleus accumbens in the rat","volume":"16","author":"Phillipson","year":"1985","journal-title":"Neuroscience"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.neuron.2014.07.002","type":"journal-article","article-title":"A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei","volume":"83","author":"Pollak Dorocic","year":"2014","journal-title":"Neuron"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s12035-011-8214-0","type":"journal-article","article-title":"Serotonin and prefrontal cortex function: neurons, networks, and circuits","volume":"44","author":"Puig","year":"2011","journal-title":"Molecular Neurobiology"},{"key":"bib78","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00026","type":"journal-article","article-title":"Risk Factors for Addiction and Their Association with Model-Based Behavioral Control","volume":"10","author":"Reiter","year":"2016","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.cell.2018.07.043","type":"journal-article","article-title":"Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems","volume":"175","author":"Ren","year":"2018","journal-title":"Cell"},{"key":"bib80","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2021.630889","type":"journal-article","article-title":"A painful beginning: Early life surgery produces long-term behavioral disruption in the rat","volume":"15","author":"Ririe","year":"2021","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"bib81","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780198524410.001.0001","type":"book","volume-title":"The Prefrontal CortexExecutive and Cognitive Functions","author":"Roberts","year":"1998"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/dev.20442","type":"journal-article","article-title":"Adolescent risk taking, impulsivity, and brain development: implications for prevention","volume":"52","author":"Romer","year":"2010","journal-title":"Developmental Psychobiology"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1037\/xge0001347","type":"journal-article","article-title":"Distinct developmental trajectories for risky and impulsive decision-making in chimpanzees","volume":"152","author":"Rosati","year":"2023","journal-title":"Journal of Experimental Psychology. General"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1038\/nn.3440","type":"journal-article","article-title":"Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating","volume":"16","author":"Rudebeck","year":"2013","journal-title":"Nature Neuroscience"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1080\/17405620701401846","type":"journal-article","article-title":"Effects of profound early institutional deprivation: An overview of findings from a UK longitudinal study of Romanian adoptees","volume":"4","author":"Rutter","year":"2007","journal-title":"European Journal of Developmental Psychology"},{"key":"bib86","doi-asserted-by":"publisher","first-page":"3108","DOI":"10.1523\/JNEUROSCI.2532-18.2019","type":"journal-article","article-title":"Prelimbic cortical neurons track preferred reward value and reflect impulsive choice during delay discounting behavior","volume":"39","author":"Sackett","year":"2019","journal-title":"The Journal of Neuroscience"},{"key":"bib87","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.11.007","type":"journal-article","article-title":"Cognitive functions associated with developing prefrontal cortex during adolescence and developmental neuropsychiatric disorders","volume":"131","author":"Sakurai","year":"2019","journal-title":"Neurobiology of Disease"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.bbr.2018.01.014","type":"journal-article","article-title":"Assessment of impulsivity in adolescent mice: A new training procedure for A 3-choice serial reaction time task","volume":"343","author":"Sasamori","year":"2018","journal-title":"Behavioural Brain Research"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"4528","DOI":"10.1523\/JNEUROSCI.4982-07.2008","type":"journal-article","article-title":"Low-serotonin levels increase delayed reward discounting in humans","volume":"28","author":"Schweighofer","year":"2008","journal-title":"The Journal of Neuroscience"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.bandc.2014.01.001","type":"journal-article","article-title":"Risk, adaptation and the functional teenage brain","volume":"89","author":"Sercombe","year":"2014","journal-title":"Brain and Cognition"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nature04513","type":"journal-article","article-title":"Intellectual ability and cortical development in children and adolescents","volume":"440","author":"Shaw","year":"2006","journal-title":"Nature"},{"key":"bib92","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/s41380-018-0260-9","type":"journal-article","article-title":"SSRIs target prefrontal to raphe circuits during development modulating synaptic connectivity and emotional behavior","volume":"24","author":"Soiza-Reilly","year":"2019","journal-title":"Molecular Psychiatry"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/13154","type":"journal-article","article-title":"In vivo evidence for post-adolescent brain maturation in frontal and striatal regions","volume":"2","author":"Sowell","year":"1999","journal-title":"Nature Neuroscience"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/1467-8721.00072","type":"journal-article","article-title":"Neurobehavioral changes in adolescence","volume":"9","author":"Spear","year":"2000","journal-title":"Current Directions in Psychological Science"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1111\/ejn.12856","type":"journal-article","article-title":"High-frequency stimulation of the medial prefrontal cortex decreases cellular firing in the dorsal raphe","volume":"41","author":"Srejic","year":"2015","journal-title":"The European Journal of Neuroscience"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.neuron.2016.09.021","type":"journal-article","article-title":"A designer aav variant permits efficient retrograde access to projection neurons","volume":"92","author":"Tervo","year":"2016","journal-title":"Neuron"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/s41583-021-00457-5","type":"journal-article","article-title":"Environmental influences on the pace of brain development","volume":"22","author":"Tooley","year":"2021","journal-title":"Nature Reviews. Neuroscience"},{"key":"bib98","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1159\/000430095","type":"journal-article","article-title":"Sequence of molecular events during the maturation of the developing mouse prefrontal cortex","volume":"1","author":"Ueda","year":"2015","journal-title":"Molecular Neuropsychiatry"},{"key":"bib99","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02188-w","type":"journal-article","article-title":"Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex","volume":"4","author":"van der Veen","year":"2021","journal-title":"Communications Biology"},{"key":"bib100","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.1093\/cercor\/bhn012","type":"journal-article","article-title":"Maturational changes in anterior cingulate and frontoparietal recruitment support the development of error processing and inhibitory control","volume":"18","author":"Velanova","year":"2008","journal-title":"Cerebral Cortex"},{"key":"bib101","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1007\/s00213-020-05454-7","type":"journal-article","article-title":"Modulation of value-based decision making behavior by subregions of the rat prefrontal cortex","volume":"237","author":"Verharen","year":"2020","journal-title":"Psychopharmacology"},{"key":"bib102","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.neuron.2020.01.017","type":"journal-article","article-title":"Inference-based decisions in a hidden state foraging task: Differential contributions of prefrontal cortical areas","volume":"106","author":"Vertechi","year":"2020","journal-title":"Neuron"},{"key":"bib103","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/nature11617","type":"journal-article","article-title":"A prefrontal cortex\u2013brainstem neuronal projection that controls response to behavioural challenge","volume":"492","author":"Warden","year":"2012","journal-title":"Nature"},{"key":"bib104","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00063","type":"journal-article","article-title":"Activation of pyramidal neurons in mouse medial prefrontal cortex enhances food-seeking behavior while reducing impulsivity in the absence of an effect on food intake","volume":"10","author":"Warthen","year":"2016","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"bib105","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neuroscience.2008.08.047","type":"journal-article","article-title":"Cognitive development in macaques: attentional set-shifting in juvenile and adult rhesus monkeys","volume":"157","author":"Weed","year":"2008","journal-title":"Neuroscience"},{"key":"bib106","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.neuron.2014.06.024","type":"journal-article","article-title":"Presynaptic partners of dorsal raphe serotonergic and gabaergic neurons","volume":"83","author":"Weissbourd","year":"2014","journal-title":"Neuron"},{"key":"bib107","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/sj.npp.1300610","type":"journal-article","article-title":"Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders","volume":"30","author":"Winstanley","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"bib108","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1111\/j.1467-8624.2006.00916.x","type":"journal-article","article-title":"Behavioral control and resiliency in the onset of alcohol and illicit drug use: A prospective study from preschool to adolescence","volume":"77","author":"Wong","year":"2006","journal-title":"Child Development"},{"key":"bib109","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65502","type":"journal-article","article-title":"Whole-brain connectivity atlas of glutamatergic and GABAergic neurons in the mouse dorsal and median raphe nuclei","volume":"10","author":"Xu","year":"2021","journal-title":"eLife"},{"key":"bib110","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.cell.2013.04.017","type":"journal-article","article-title":"Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males","volume":"153","author":"Yang","year":"2013","journal-title":"Cell"},{"key":"bib111","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59551","type":"journal-article","article-title":"Laminar-specific cortico-cortical loops in mouse visual cortex","volume":"10","author":"Young","year":"2021","journal-title":"eLife"},{"key":"bib112","doi-asserted-by":"publisher","first-page":"3018","DOI":"10.1016\/j.celrep.2017.02.077","type":"journal-article","article-title":"Organization of functional long-range circuits controlling the activity of serotonergic neurons in the dorsal raphe nucleus","volume":"18","author":"Zhou","year":"2017","journal-title":"Cell Reports"},{"key":"bib113","doi-asserted-by":"publisher","first-page":"15034","DOI":"10.1523\/JNEUROSCI.2612-10.2010","type":"journal-article","article-title":"Growing together and growing apart: regional and sex differences in the lifespan developmental trajectories of functional homotopy","volume":"30","author":"Zuo","year":"2010","journal-title":"The Journal of Neuroscience"},{"key":"bib114","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.tics.2016.10.005","type":"journal-article","article-title":"Human connectomics across the life span","volume":"21","author":"Zuo","year":"2017","journal-title":"Trends in Cognitive Sciences"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/93485\/elife-93485-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/93485\/elife-93485-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/93485","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:35:25Z","timestamp":1787567725000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/93485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":114,"alternative-id":["10.7554\/eLife.93485"],"URL":"https:\/\/doi.org\/10.7554\/elife.93485","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.01.01.474690","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.01.01.474690","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.93485.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.93485.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.93485.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e93485"}}