Objective To study the effect of ghrelin gene knockout on the postsynaptic potential of dopaminergic neurons in the substantia nigra of mice. Methods Substantia nigra tissue was taken from 10-week-old ghrelin-/- male mice (ghrelin-/- group) and their male wild-type (WT) littermates (WT group). RNA-seq technique was used to screen differently expressed genes (DEGs). KEGG pathway enrichment analysis was performed for the neuronal synaptic activity-associated signaling pathways which DEGs might be involved in. Quantitative real-time PCR (RT-qPCR) was used for validation of the identified DEGs, and western blotting was used for protein expression of neuronal synaptic activity-related genes. Results Compared with the WT group, the ghrelin-/- group had significant changes in the expression levels of 23 genes in the synaptic signaling pathway of dopaminergic neurons. Specifically, Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid type subunit 3 (GluA3) and glycogen synthase kinase3-β (GSK-3β) regulated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor and N-methyl-D-aspartic acid receptor on the postsynaptic membrane of neurons, respectively. GluA3 and GSK-3β genes were significantly downregulated in the substantia nigra tissue of mice in the ghrelin-/- group. RT-qPCR results showed that compared to the WT group, the ghrelin-/- group had significant downregulation of the mRNA expression levels of GluA3 and GSK-3β in the substantia nigra tissue of mice (t =2.408,2.740,P<0.05). Western blotting results showed that compared with the WT group, the ghrelin-/- group had a significantly upregulated expression level of GluA3 protein (t=2.530,P<0.05) and a significantly downregulated expression level of GSK-3β protein (t=3.469,P<0.05) in the substantia nigra tissue of mice. Conclusion Ghrelin gene knockout may enhance the excitatory synaptic transmission activity by enhancing the postsynaptic potential of substantia nigra dopaminergic neurons in mice for a long time, thus regulating movement
