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Publication : Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit.

First Author  Anthony TE Year  2014
Journal  Cell Volume  156
Issue  3 Pages  522-36
PubMed ID  24485458 Mgi Jnum  J:333398
Mgi Id  MGI:7434894 Doi  10.1016/j.cell.2013.12.040
Citation  Anthony TE, et al. (2014) Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit. Cell 156(3):522-36
abstractText  The extended amygdala has dominated research on the neural circuitry of fear and anxiety, but the septohippocampal axis also plays an important role. The lateral septum (LS) is thought to suppress fear and anxiety through its outputs to the hypothalamus. However, this structure has not yet been dissected using modern tools. The type 2 CRF receptor (Crfr2) marks a subset of LS neurons whose functional connectivity we have investigated using optogenetics. Crfr2(+) cells include GABAergic projection neurons that connect with the anterior hypothalamus. Surprisingly, we find that these LS outputs enhance stress-induced behavioral measures of anxiety. Furthermore, transient activation of Crfr2(+) neurons promotes, while inhibition suppresses, persistent anxious behaviors. LS Crfr2(+) outputs also positively regulate circulating corticosteroid levels. These data identify a subset of LS projection neurons that promote, rather than suppress, stress-induced behavioral and endocrinological dimensions of persistent anxiety states and provide a cellular point of entry to LS circuitry.
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