Locus coeruleus-CA1 projections are involved in chronic depre

hM3Dq-mCherry and hM4Di-mCherry were used to selectively silence or active the Th:LC-CA1 circuit respectively. ChR2-EYFP was used for direct output projections in LC-TH+ neurons. (All viruses were packaged by BrainVTA)

The viruses used in this article from BrainVTA are in the table below

Chemogenetics	PT-0042 AAV-Ef1a-DIO-hM3Dq-mCherry PT-0043 AAV-Ef1a-DIO-hM4Di-mCherry
Control	PT-0013 AAV-Ef1a-DIO-mCherry
CRE Recombinase	PT-0179 AAV-TH-Cre
Optogenetic	PT-0001 AAV-Ef1α-DIO-hChR2(H134R)-EYFP

Qian Zhang, Dian Xing Hu, Feng He, Chun Yang Li, Guang Jian Qi, HongWei Cai, Tong Xia Li, Jie Ming, Pei Zhang, Xiao Qian Chen & Bo Tian
Pub Date: 2019-06-03, DOI: 10.1038/s41467-019-10795-9， Email: [email protected]
Depression and transient ischaemic attack represent the common psychological and neurological diseases, respectively, and are tightly associated. However, studies of depression-affected ischaemic attack have been limited to epidemiological evidences, and the neural circuits underlying depression-modulated ischaemic injury remain unknown. Here, we ﬁnd that chronic social defeat stress (CSDS) and chronic footshock stress (CFS) exacerbate CA1 neuron loss and spatial learning/memory impairment after a short transient global ischaemia (TGI) attack in mice. Whole-brain mapping of direct outputs of locus coeruleus (LC)-tyrosine hydroxylase (TH, Th:) positive neurons reveals that LC-CA1 projections are decreased in CSDS or CFS mice. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools, we determine that Th:LC-CA1 circuit is necessary and sufﬁcient for depression-induced aggravated outcomes of TGI. Collectively, we suggest that Th:LC-CA1 pathway plays a crucial role in depression-induced TGI vulnerability and offers a potential intervention for preventing depression-related transient ischaemic attack.

Fig. 1 Whole-brain quantitative mapping of direct outputs from LC-TH+ neurons in CSDS.

To investigate the effect of depression on ischaemia-caused neurological disorders and to ascertain the underlying neural circuit mechanism, using virus-mediated whole-brain circuit mapping, the results reveal a previously undeﬁned role for Th:LC-CA1 projections in how depression increases TGI vulnerability. These results provide a critical framework for understanding the downstream inﬂuence of the LC system in the CA1 region as it relates to spatial learning and memory.

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