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The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release. Fil: Dedic, Nina. Max Planck Institute Of Psychiatry; Alemania Fil: Kühne, Claudia. Max Planck Institute Of Psychiatry; Alemania Fil: Jakovcevski, Mira. Max Planck Institute Of Psychiatry; Alemania Fil: Hartmann, Jakob. Max Planck Institute Of Psychiatry; Alemania Fil: Genewsky, Andreas J.. Max Planck Institut Of Psychiatry; Alemania Fil: Gomes, Karina S.. Max Planck Institute Of Psychiatry; Alemania Fil: Anderzhanova, Elmira. Max Planck Institute Of Psychiatry; Alemania Fil: Pöhlmann, Max L.. Max Planck Institute Of Psychiatry; Alemania Fil: Chang, Simon. Max Planck Institute Of Psychiatry; Alemania Fil: Kolarz, Adam. Max Planck Institute Of Psychiatry; Alemania Fil: Vogl, Annette M.. Max Planck Institute Of Psychiatry; Alemania Fil: Dine, Julien. Max Planck Institute Of Psychiatry; Alemania Fil: Metzger, Michael W.. Max Planck Institute of Psychiatry; Armenia Fil: Schmid, Bianca. Max Planck Institute Of Psychiatry; Alemania Fil: Almada, Rafael C.. Max Planck Institute Of Psychiatry; Alemania Fil: Ressler, Kerry J.. Harvard Medical School; Estados Unidos Fil: Wotjak, Carsten T.. Max Planck Institute Of Psychiatry; Alemania Fil: Grinevich, Valery. University of Heidelberg; Alemania Fil: Chen, Alon. Max Planck Institute Of Psychiatry; Alemania Fil: Schmidt, Mathias V.. Institute Of Developmental Genetics, Helmholtz Zentrum; Alemania Fil: Wurst, Wolfgang. German Center for Neurodegenerative Diseases; Alemania Fil: Refojo, Damian. Max Planck Institute Of Psychiatry; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Deussing, Jan M.. Max Planck Institute Of Psychiatry; Alemania

Proliferative cells expressing proteoglycan neuron-glia 2 (NG2) are considered to represent parenchymal precursor cells in the adult brain and are thought to differentiate primarily into oligodendrocytes. We have studied cell genesis in the adult amygdala and found that, up to 1 year after the labeling of proliferating cells with bromodeoxyuridine, most proliferating NG2 cells remain NG2 cells, and only a few slowly differentiate into mature oligodendrocytes, as assessed by the expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase. We have detected no signs of neurogenesis but have confirmed the expression of "neuronal" markers such as Doublecortin in NG2 cells. Nestin-expressing NG2 cells in the amygdala show electrophysiological properties known for oligodendrocyte precursor cells in the corpus callosum. Application of the glutamate agonist kainate elicits a "complex" response consisting of a rapid and long-lasting blockade of the resting K(+) conductance, a transient cationic current, and a transient increase of an outwardly directed K(+) conductance, suggesting the responsiveness of NG2 cells to excitation. Proliferation of NG2 cells increases in response to behavioral stimuli of activity, voluntary wheel running, and environmental enrichment. In addition to reducing the number of newborn microglia, behavioral activity results in a decrease in S100beta-expressing newborn NG2 cells in the amygdala. Because S100beta expression in NG2 cells ceases with oligodendrocyte maturation, this finding suggests that NG2 cells in the amygdala undergo activity-dependent functional alterations, without resulting in a measurable increase in new mature oligodendrocytes over the time period covered by the present study. The adult amygdala thus shows signs of mixed activity-dependent plasticity: reduced numbers of microglia and, presumably, an altered fate of NG2 cells.