000279437 001__ 279437 000279437 005__ 20250720001546.0 000279437 0247_ $$2doi$$a10.1038/s41467-025-61018-3 000279437 0247_ $$2pmid$$apmid:40592902 000279437 0247_ $$2pmc$$apmc:PMC12216545 000279437 0247_ $$2altmetric$$aaltmetric:178751284 000279437 037__ $$aDZNE-2025-00768 000279437 041__ $$aEnglish 000279437 082__ $$a500 000279437 1001_ $$00000-0001-7513-1396$$aMartínez-Rojas, Beatriz$$b0 000279437 245__ $$aStimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation. 000279437 260__ $$a[London]$$bSpringer Nature$$c2025 000279437 3367_ $$2DRIVER$$aarticle 000279437 3367_ $$2DataCite$$aOutput Types/Journal article 000279437 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1752563788_3119 000279437 3367_ $$2BibTeX$$aARTICLE 000279437 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000279437 3367_ $$00$$2EndNote$$aJournal Article 000279437 520__ $$aAfter spinal cord injury (SCI), cyclic adenosine monophosphate (cAMP) levels drop in the spinal cord, cortex and brainstem, unlike in regenerating peripheral neurons. To address SCI recovery, we expressed photoactivatable adenylate cyclase (bPAC) in corticospinal neurons of female rats with dorsal hemisection for on-demand cAMP inductions. bPAC stimulation restored passive and firing properties of corticospinal neurons, promoted early and sustained locomotor recovery and increased corticospinal tract plasticity. Additionally, bPAC enhanced sparing of lumbar-projecting brainstem neurons after SCI, accompanied by activation of cAMP signaling in the raphe-reticular formation and increased excitatory/inhibitory neurotransmitter balance. Accordingly, augmented density of serotonergic tracts was found caudal to the injury in bPAC rats, correlating with enhanced functional performance. Serotonergic implication in motor recovery was further evidenced by selective depletion, resulting in the abrogation of bPAC-mediated recovery. Overall, our findings underscore that cAMP induction in corticospinal neurons enhances locomotion after SCI, through a cortical rerouting pathway via the serotonergic descending tract. 000279437 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0 000279437 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000279437 650_7 $$0E0399OZS9N$$2NLM Chemicals$$aCyclic AMP 000279437 650_7 $$0EC 4.6.1.1$$2NLM Chemicals$$aAdenylyl Cyclases 000279437 650_2 $$2MeSH$$aAnimals 000279437 650_2 $$2MeSH$$aFemale 000279437 650_2 $$2MeSH$$aSpinal Cord Injuries: physiopathology 000279437 650_2 $$2MeSH$$aSpinal Cord Injuries: metabolism 000279437 650_2 $$2MeSH$$aSpinal Cord Injuries: therapy 000279437 650_2 $$2MeSH$$aCyclic AMP: metabolism 000279437 650_2 $$2MeSH$$aPyramidal Tracts: metabolism 000279437 650_2 $$2MeSH$$aPyramidal Tracts: physiopathology 000279437 650_2 $$2MeSH$$aOptogenetics: methods 000279437 650_2 $$2MeSH$$aRats 000279437 650_2 $$2MeSH$$aRecovery of Function: physiology 000279437 650_2 $$2MeSH$$aAdenylyl Cyclases: metabolism 000279437 650_2 $$2MeSH$$aAdenylyl Cyclases: genetics 000279437 650_2 $$2MeSH$$aNeurons: metabolism 000279437 650_2 $$2MeSH$$aNeurons: physiology 000279437 650_2 $$2MeSH$$aRats, Sprague-Dawley 000279437 650_2 $$2MeSH$$aLocomotion: physiology 000279437 650_2 $$2MeSH$$aSerotonergic Neurons: metabolism 000279437 650_2 $$2MeSH$$aNeuronal Plasticity 000279437 7001_ $$00009-0007-7062-8695$$aMartín-Pérez, Samuel$$b1 000279437 7001_ $$00000-0001-5488-3011$$aGiraldo, Esther$$b2 000279437 7001_ $$00000-0001-8206-9869$$aLopez-Mocholi, Eric$$b3 000279437 7001_ $$aAlastrue, Ana$$b4 000279437 7001_ $$00000-0002-5295-0169$$aAndrade-Talavera, Yuniesky$$b5 000279437 7001_ $$aPrius-Mengual, Jose$$b6 000279437 7001_ $$00000-0003-2292-5330$$aPaniagua, Guillem$$b7 000279437 7001_ $$aPedraza, Maria$$b8 000279437 7001_ $$aHingorani, Sonia$$b9 000279437 7001_ $$0P:(DE-2719)2810914$$aRost, Benjamin R$$b10 000279437 7001_ $$0P:(DE-2719)2810725$$aSchmitz, Dietmar$$b11$$udzne 000279437 7001_ $$00000-0002-5565-5907$$aLlansola, Marta$$b12 000279437 7001_ $$00000-0003-3145-9538$$aFelipo, Vicente$$b13 000279437 7001_ $$00000-0002-8078-6175$$aRodríguez-Moreno, Antonio$$b14 000279437 7001_ $$00000-0002-6035-9491$$aMoreno-Manzano, Victoria$$b15 000279437 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-61018-3$$gVol. 16, no. 1, p. 5885$$n1$$p5885$$tNature Communications$$v16$$x2041-1723$$y2025 000279437 8564_ $$uhttps://pub.dzne.de/record/279437/files/DZNE-2025-00768%20SUP.zip 000279437 8564_ $$uhttps://pub.dzne.de/record/279437/files/DZNE-2025-00768.pdf$$yOpenAccess 000279437 8564_ $$uhttps://pub.dzne.de/record/279437/files/DZNE-2025-00768.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000279437 909CO $$ooai:pub.dzne.de:279437$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000279437 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810914$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b10$$kDZNE 000279437 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810725$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE 000279437 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x0 000279437 9141_ $$y2025 000279437 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-02 000279437 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-02 000279437 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-01-02 000279437 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-01-02 000279437 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000279437 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2025-01-02 000279437 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bNAT COMMUN : 2022$$d2025-01-02 000279437 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT COMMUN : 2022$$d2025-01-02 000279437 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-01-30T07:48:07Z 000279437 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-01-30T07:48:07Z 000279437 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - 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