Table 2.

Summary of hippocampal molecules involved in anxiety modulation.

Examples	Subfields	Anxiety-regulating functions	References
Channel protein
HCN1	dCA1	The anxiolytic effect of HCN1 knockdown.	[105]
HCN4	dHPC	Anxiogenic effect of HCN4 knockdown.	[104]
Neurotransmitter systems
NMDAR	vHPC	NMDAR agonists increased anxiety.	[158]
		NMDAR antagonists reduced anxiety.
GABAAR	vHPC	GABAAR agonists reduced anxiety.	[158]
		GABAAR antagonists increased anxiety.
AChE	vHPC	AChE inhibitor alleviated anxiety.	[160]
	HPC	knockdown of AChE increased anxiety	[161]
D1/D2R	vHPC	The anxiolytic effect of D1/D2R antagonists.	[165]
	vCA3	Anxiogenic effect of D1/D2R antagonists.	[167]
nNOS	HPC	Chronic stress increased the level and activity of hippocampal nNOS	[168]
		Enhancement of nNOS-CAPON coupling is anxiogenic.	[168]
			[169]
	vHPC	Downregulating of nNOS is anxiolytic.	[171]
AEA /CB1R	HPC	Enhancement of the ECBs signaling is anxiolytic.	[174]
			[177]
	vHPC	Reduced CB1R in GABAergic neurons and activated CB1R in glutamatergic neurons are anxiolytic	[178]
Neuropeptide systems
CRH/CRHR1	dHPC	Intervention with CRHR1 is anxiolytic.	[182]
	vHPC	CRHR1 antagonist is anxiolytic.	[183]
NPS	vHPC	The anxiolytic effect of NPS.	[184]
			[185]
			[186]
RXFP3	vHPC	Anxiogenic effect of RXFP3 agonists.	[187]
Cytokine
IL-1β	DG	Increasing IL-1β is anxiogenic.	[189]
NLRP3	vHPC	Deletion of NLRP3 is anxiogenic.	[192] [193]
	vHPC	Activation of microglial NLRP3 in CMS.	[194]

HCN, hyperpolarization-activated cyclic-nucleotide-gated channels; NMDAR, N-methyl-D-aspartate receptor; GABA_AR, gamma amino butyric acid A receptor; AChE, acetylcholinesterase; D1/D2R, dopamine D1 and D2 receptor; 5-HT₄R, 5-hydroxytryptamine 4 receptor; 5-HT_1AR, 5-HT_1A receptor; 5-HT_2CR, 5-HT_2C receptor; nNOS, neuronal nitric oxide synthase; CAPON, carboxy-terminal PDZ ligand; AEA, arachidonoyl ethanolamide or anandamide; CB1R, cannabinoid 1 receptor; ECB, endocannabinoid; CRH, corticotropin-releasing hormone; CRHR1, corticotropin-releasing hormone receptor 1; NPS, neuropeptide S; RXFP3, relaxin-family peptide 3 receptor; IL-1β, interleukin-1β; NLRP3, nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3; HPC, hippocampus; dHPC, dorsal HPC; vHPC, ventral HPC; DG, dentate gyrus; dCA1, dorsal cornu ammonis 1; vCA3, ventral cornu ammonis 3.