期刊
JOURNAL OF NEUROSCIENCE
卷 40, 期 20, 页码 3949-3968出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0270-20.2020
关键词
BNST; CRF; extended amydala; GluN2D; mood disorders; NMDAR
资金
- National Institutes of Health [CA68485, DK20593, DK58404, DK59637, EY08126, T32 MH064913, R37 AA019455]
- National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award
- National Institutes of Health INIA Stress Core [U24AA025475]
Excitatory signaling mediated by NMDARs has been shown to regulate mood disorders. However, current treatments targeting NMDAR subtypes have shown limited success in treating patients, highlighting a need for alternative therapeutic targets. Here, we identify a role for GluN2D-containing NMDARs in modulating emotional behaviors and neural activity in the bed nucleus of the stria terminalis (BNST). Using a GluN2D KO mouse line (GluN2D(-/-)), we assessed behavioral phenotypes across tasks modeling emotional behavior. We then used a combination of ex vivo electrophysiology and in vivo fiber photometry to assess changes in BNST plasticity, cell-specific physiology, and cellular activity profiles. GluN2D(-/-) male mice exhibit evidence of exacerbated negative emotional behavior, and a deficit in BNST synaptic potentiation. We also found that GluN2D is functionally expressed on corticotropin-releasing factor (CRF)-positive BNST cells implicated in driving negative emotional states, and recordings in mice of both sexes revealed increased excitatory and reduced inhibitory drive onto GluN2D(-/-) BNST-CRF cells ex vivo and increased activity in vivo. Using a GluN2D conditional KO line (GluN2D(flx/flx)) to selectively delete the subunit from the BNST, we find that BNST-GluN2D(flx/flx) male mice exhibit increased depressive-like behaviors, as well as altered NMDAR function and increased excitatory drive onto BNST-CRF neurons. Together, this study supports a role for GluN2D-NMDARs in regulating emotional behavior through their influence on excitatory signaling in a region-specific manner, and suggests that these NMDARs may serve as a novel target for selectively modulating glutamate signaling in stress-responsive structures and cell populations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据