PT  - JOURNAL ARTICLE
AU  - Morales, Lorena
AU  - Castro-Robles, Beatriz
AU  - Abellán, Antonio
AU  - Desfilis, Ester
AU  - Medina, Loreta
TI  - A novel telencephalon-opto-hypothalamic morphogenetic domain produces most of the glutamatergic neurons of the medial extended amygdala
AID  - 10.1101/2020.07.17.207936
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.17.207936
4099  - http://biorxiv.org/content/early/2020/07/17/2020.07.17.207936.short
4100  - http://biorxiv.org/content/early/2020/07/17/2020.07.17.207936.full
AB  - Deficits in social cognition and behavior are a hallmark of many psychiatric disorders. The medial extended amygdala, including the medial amygdala and the medial bed nucleus of the stria terminalis, is a key component of functional networks involved in sociality. However, this nuclear complex is highly heterogeneous and contains numerous GABAergic and glutamatergic neuron subpopulations. Deciphering the connections of different neurons is essential in order to understand how this structure regulates different aspects of sociality, and it is necessary to evaluate their differential implication in distinct mental disorders. Developmental studies in different vertebrates are offering new venues to understand neuronal diversity of the medial extended amygdala, and are helping to establish a relation between the embryonic origin and molecular signature of distinct neurons with the functional subcircuits in which they are engaged. These studies have provided many details on the distinct GABAergic neurons of the medial extended amygdala, but information on the glutamatergic neurons is still scarce. Using an Otp-eGFP transgenic mouse and multiple fluorescent labeling, we show that most glutamatergic neurons of the medial extended amygdala originate in a novel telencephalo-opto-hypothalamic embryonic domain (TOH), located at the transition between telencephalon and hypothalamus, which produces Otp-lineage neurons expressing the telencephalic marker Foxg1 but not Nkx2.1 during development. These glutamatergic cells include a subpopulation of projection neurons of the medial amygdala, which activation has been previously shown to promote autistic-like behavior. Our data open new venues for studying the implication of this neuron subtype in neurodevelopmental disorders producing social deficits.Competing Interest StatementThe authors have declared no competing interest.AAvventral anterior amygdalaacanterior commissureAHanterior hypothalamusBCamygdalar basolateral complexBMabasomedial amygdala, anterior subnucleusBSTMmedial bed nucleus of the stria terminalisBSTMaBSTM, anterior divisionBSTMhBSTM, hypothalamic subdivision/ hypothalamic subdivision of BSTMBSTMpBSTM, posterior divisionBSTLlateral bed nucleus of the stria terminalisCecentral nucleus of the amygdala (or simply central amygdala)CercerebellumCPucaudate-putamen complexDMdorsomedial hypothalamic nucleusEMmedian eminenceESOepisupraoptic nucleusffornixGPglobus pallidusHFhippocampal formationHyaalar hypothalamusHybbasal hypothalamusLHlateral hypothalamusLHbasal LHLOTnucleus of the lateral olfactory tractLPOlateral preoptic arealvlateral ventriclemmantleMamammillary nucleiMemedial nucleus of the amygdala (or simply, medial amygdala)MeAanterior subnucleus of MeMePposterior subnucleus of MeMePDdorsal subnucleus of MePMePVventral subnucleus of MePMePVmmedial branch of MePVMePVllateral branch of MePVMGEvcmedial glaglionic eminence, ventrocaudal subdivisionNHneurohypophysisOBolfactory bulbocoptic chiasmopoptic pedicleotoptic tractPpalliumPadparaventricular nucleus, dorsal subdivisionPavparaventricular nucleus, ventral subdivisionPtpretectumPHypeduncular hypothalamusPOPeperiventricular part of the preoptic areaPOssubpallial preoptic areaPOvventral preoptic areaPThprethalamusPThEprethalamic eminencePVNparaventricular nucleus, principal subdivisionSeseptumSEAsublenticular extended amygdalaSOsupraoptic nucleus, principal subdivisionSOtsupraoptic nucleus, terminal subdivisionSOtuof the supraoptic nucleus, tuberal subdivisionSpsubpalliumSCsuperior colliculusSCNsuprachiasmatic nucleusSPasubparaventricular regionSPVsupraopto-paraventricular hypothalamic domain (classical definition)SPVcsupraopto-paraventricular hypothalamic domain, core partsvzsubventricular zoneTeltelencephalonThthalamusTHyterminal hypothalamusTOHtelencephalo-opto-hypothalamic embryonic domainVMHventromedial hypothalamic nucleusvzventricular zone3vthird ventricle4vfourth ventricle