PT - JOURNAL ARTICLE AU - Krisztina Horváth AU - Balázs Juhász AU - Dániel Kuti AU - Szilamér Ferenczi AU - Bibiána Török AU - Dóra Zelena AU - Krisztina J. Kovács TI - Recruitment of Corticotropin-releasing Hormone CRH Neurons in response to Categorically Distinct Stress Challenges in the Mouse Brain AID - 10.1101/2022.01.20.477065 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.01.20.477065 4099 - http://biorxiv.org/content/early/2022/01/21/2022.01.20.477065.short 4100 - http://biorxiv.org/content/early/2022/01/21/2022.01.20.477065.full AB - Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (Pa) are in the position to integrate stress-related information and initiate adaptive neuroendocrine-, autonomic-, metabolic- and behavioral responses. In addition to hypophyseotropic cells, CRH is widely expressed in the CNS, however their involvement in organization of the stress response is not fully understood. In these experiments, we took the advantage of recently available Crh-IRES-Cre; Ai9 mouse line to study the recruitment of hypothalamic and extrahypothalamic CRH neurons in categorically distinct, acute stress reactions. Reporter mice were exposed to restraint, ether, high salt and lipopolisacharide stress. The induced activation of CRH neurons was detected by colocalization of immediate early gene c-Fos in Td tomato expressing cells. We found differential activation of CRH neurons in central amygdaloid nucleus (Ce), bed nucleus stria terminalis lateral division, ventral posterior (BSTLVP), medial preoptic nucleus (MPO), ventromedial hypothalamic nucleus (VMH), premammillary nucleus (PM) and prepositus hypoglossal nucleus (Pr) in response to physiological (ether, high salt and LPS) and psychological (restraint) stressors. CRH positive cells in Pa became activated, however in the Barrington’s nucleus and locus coeruleus no actiovation could be observed due to most tested stressors. Furthermore no CRH neuron activation occured in dorsal (BSTLD) and posterior (BSTLP) region of lateral division of bed nucleus stria terminalis after restraint stress. In the inferior olive only ether exposition resulted in CRH neuron activation. These results confirm activation of CRH neurons in the Pa, reveals new subset of stress-related CRH cells through the mouse brain and disprove the recruitment of CRH cells in the SOL and in the Barrington’s nucleus to acute psychological stress in mice.Competing Interest StatementThe authors have declared no competing interest.Acbaccumbens nuAlagranular insular cortexAcoanterior cortical amygdaloid nucleusAHCanterior hypothalamic area, centralAHPanterior hypothalamic area, posteriorAOanterior olfactory nucleusArcarcuate hypothalamic nucleusAParea postremaBarBarrington’s nucleusBACbed nucleus anterior commissureBSTbed nucleus stria terminalisBSTLDbed nucleus stria terminalis, lat div, dorsBSTLPbed nucleus stria terminalis, lat div, postBSTLVPbed nucleus stria terminalis, lat div, vent posteriorCA3CA3 field, hippocampusCecentral amygdaloid nucleusCGcentral grayCMcentral medial thalamic nucleusCgcingulate cortexClclaustrumCcochlear nucleusCucuneate nucleusDpMedeep mesencephalic nucleusDGdentate gyrusDENdorsal endopiriform nu10dorsal motor nucleus vagus nerveDPdorsal peduncular cortexDTrdorsal transition zoneDMdorsomedial hypothalamic nucleusDMPndorsomedial pontinue nucleusEWEdinger-Westphal nucleusEcuexternal cunate nucleusEPIOexternal plexiform layer, olfactory bulbGgeniculate nucleusGIgranular insular cortexGrOgranule layer, olfactory bulbHChippocampusHDBhorizontal diagonal band12hypoglossal nucleusIOinferior oliveILinfralimbic cortexIADinteranterior dorsal thalamic nucleusIFinterfascicular nucleusIPRinterpeduncular nucleus, rostral subnucleusIPACinterstit nucleus post limb ant comLVOVlateral and ventral orbital cortex ventral partLHlateral hypothalamic areaLRtlateral reticular nucleus, ventrolateral medullaLSlateral septal nucleusLClocus coeruleusMCLHDmagnocellular nucleus, lateral hypothalamic area dorsal partMCLHVmagnocellular nucleus, lateral hypothalamic area ventral partMemedial amygdaloid nucleusMPOmedial preoptic nucleusMVePCmedial vestibular nucleus, parvicellularMnRmedian raphe nucleusLOTnucleus lateral olfactory tractXnucleus XOorbital cortexPSThparasubthalamic nucleusPaparaventricular hypothalamic nucleusPVAparaventricular thalamic nucleus, anteriorPVPparaventricular thalamic nucleus, posteriorPAGperiaqueductal grayPeFperifornical nucleusPirpiriform cortexPnpontine nucleiPHDposterior hypothalamic area, dorsal partPHposterior hypothalamic area, posteriorPHVposterior hypothalamic area, ventral partPILposterior intralaminar thalamic nucleusPMTHposteromedial thalamic areaPMTNposteromedial thalamic nucleusPrCprecomissural nucleusPrLprelimbic cortexPMpremammillary nucleusPrprepositus hypoglossal nucleusM1primary motor cortexRparaphe pallidus nucleusRtTgreticulotegmental nucleus ponsRSretrosplenial cortexRhrhomboid thalamic nucleusM2secondary motor cortexS2secondary somatosensory cortexSolsolitary tract nucleusS1somatosensory 1SThsubthalamic nucleusSCsuperior colliculusSChsuprachiasm nucleusSOsupraoptic nucleusSusuprmammillary nucleusVTTventral tenia tectaVLGventrolateral genic nucleusVMHventromedial hypothalamic nucleusVMPAventromedial preoptic area + OVLTZIzona incerta