Table 1.

Summary of studies on depression examining optogenetic and chemogenetic approaches.

Region	Neuron’s type	Model	Neuromdoulation method	Primary findings	References
VTA	DA	CUMS	Optogenetic	Suggesting a positive correlation between VTA DAergic neuronal activity and depression-like behaviors in mice	Tye et al. (2012)
VTA	DA	TH−/− mice	Chemogenetic	The antidepressant mechanism of VTA-DA neurons is characterized by an increase in VTA DA neuronal activity, leading to enhanced dopamine release. This, in turn, restores cAMP signaling, resulting in elevated levels of tyrosine hydroxylase phosphorylation and ultimately ameliorating depressive-like behaviors in mice	Zhong et al. (2014)
NAC	Drd1	CSDS	Optogenetic	Indicating that Drd1-MSNs in the NAc can bidirectionally regulate depression-like behaviors in mice	Francis et al. (2015)
VTA-NAC	DA	Pain	Chemogenetic	Activation of VTA-NAc DAergic neurons can improve depression-like behaviors in mice	Markovic et al. (2021)
OT	Drd3	CRS	Optogenetic	Suggesting that OT-Drd3 neurons may exert antidepressant effects by modulating the VTA-NAc circuit	Zhang et al. (2023)
VTA-mPFC	DA	CSDS	Optogenetic	Suggesting a positive correlation between VTA-mPFC DAergic neuronal activity and depression-like behaviors in mice	Chaudhury et al. (2012)
mPFC	GABA, pv, sst, Glu	CUMS	Chemogenetic	Suggesting that excessive inhibition of glutamatergic pyramidal neurons by GABAergic interneurons within the mPFC, including their major subtypes, parvalbumin (PV)- and somatostatin (SST)-containing interneurons, contributes to depression-like behaviors in mice	Fogaça et al. (2020)
mPFC-LHB	GABA	CSDS	chemogenetic	Suggesting that mPFC-LHB GABAergic interneurons can exert a modulatory influence on depression-like behavior in mice.	(Lin et al., 2022)
mPFC-LHB	GABA	Itpr2−/− mice	Chemogenetic	Providing further evidence that ATP exerts antidepressant effects by inhibiting GABAergic interneurons within the mPFC-LHB circuit	Lin et al. (2022)
mPFC	Drd1	FST	Optogenetic	Suggesting that ketamine exerts its antidepressant action through the activation of Drd1 neurons in the mPFC	Hare et al. (2019)
mPFC-BLA	Drd1	FST	Optogenetic	Suggesting a positive correlation between mPFC-BLA Drd1 neuronal activity and depression-like behaviors in mice	Hare et al. (2019)
DG	ABINS	CUMS	Chemogenetic	Suggesting that the rapid antidepressant effects of ketamine are mediated by the activation of adult-born immature granule neurons (ABINs) within the DG	Rawat et al. (2022)
vHIP-mPFC	None	FST	Optogenetic	Suggesting that TrkB exerts its antidepressant effects by modulating the activity of the vHIP-mPFC circuit	Carreno et al. (2015)
DRN	5-HT	FST	Optogenetic	Suggesting that the activation of DRN 5-HT neurons directly produces antidepressant effects	Nishitani et al. (2018)
DRN-VTA	5-HT	CSDS	Optogenetic	Suggesting that DRN-VTA 5-HT neurons can bidirectionally regulate depression-like behaviors in mice	Nagai et al. (2023)
DRN	MC4R	MC4R−/−	Chemogenetic	Suggesting a positive correlation between DRN MC4R neuronal activity and depression-like behaviors in mice, highlighting the close association between depression and obesity	Bruschetta et al. (2020)
LHB	None	CSDS	Chemogenetic	Suggesting that the antidepressant mechanism of SSRIs involves the inhibition of LHB neuronal activity	Sachs et al. (2015)
LH-LHB	Glu	CRS	Chemogenetic, optogenetic	Suggesting an inverse relationship between the activity of LH-LHB glutamatergic neurons and depressive-like behaviors in mice	Zheng et al. (2022)
Ent-DG	Glu	CSDS	Chemogenetic	Suggesting an inverse relationship between the activity of Ent-DG glutamatergic neurons and depressive-like behaviors in mice	Yun et al. (2018)
Ent Va-V2M	None	CSDS	Optogenetic	These findings support the bidirectional regulation of depression-like behaviors by the Ent-V2M Va neurons	Lu et al. (2022)
SI-LHB	Glu	CUMS	Chemogenetic, optogenetic	Suggesting a positive correlation between SI-LHB glutamatergic neuronal activity and depression-like behaviors in mice	Cui et al. (2022)