Effect Of Muscarinic Cholinergic Receptor Activity On Synaptic Transmission Of SST And PV Interneurons In The Anterior Cingulate Cortex

Objective:Major depression disorder(MDD)as an emotional persistent low thinking slow motility inhibition as the core symptoms of mental illness,has already been one of the main causes of the world disabled and poor health,and the social and economic burden on the health care system is severely increased because of its poor treatment effect,so the current drug research and treatment of depression has been urgently needed.In many patients with depression,the significant decreased volume of the anterior cingulate cortex,the decreased number of synapses,the decreases in synaptic transmission,and the weakened connections between the anterior cingulate cortex and its neural networks,suggesting that the connections between the anterior cingulate cortex and its neural networks may be important targets for depression.Human and animal researches have indicated that scopolamine is a nonspecific muscarinic cholinergic receptor(m ACh R)antagonist,which has a rapid antidepressant effect.Muscarinic cholinergic receptors are commonly found in the anterior cingulate cortex,and the mechanism of their action in antidepressant therapy is still unknown.GABAergic interneruons in the medial prefrontal cortex and anterior cingulate cortex play an important role in major depression,but how the synaptic activity of GABAergic interneruons is affected by m ACh R activity remains to be further investigated.In this study,we activated or antagonized m-type choline receptors by muscarine and scopolamine,so as to investigate the effect of m ACh R activity on synaptic transmission of both somatostatin(SST)and parvalbumin(PV)containing interneurons in the ACC.Methods: We obtained transgenic SST-cre mice and PV-cre mice by gene hybridization,and identified the mouse germline by brain block cell staining and polymerase chain reaction(PCR).With immunofluorescence staining test target record between SST and PV cells and their position in the ACC,with brain slice of patch clamp electrophysiological technique a muscarinic cholinergic receptor activation or antagonism between the PV and SST neuronal excitatory and inhibitory synaptic transmission,and through adulthood and adolescence C57BL/6J mice with genetically modified(gm)SST-cre mice celiac injection of scopolamine(3 mg/kg),by forced swimming test,tests immobilized behaviors in mice and repeats scopolamine in the rapid antidepressant action experimental results.Results: We found that muscarine,in the patch clamp electrophysiological test,an agonist of m ACh R significantly affected frequency,but not amplitude,of s EPSCs(p < 0.01),but not m EPSCs(p > 0.05),was significantly increased by bath application of muscarine in both SST and PV interneurons.The effect was blocked by scopolamine,an antagonist of m ACh R.Bath application of scopolamine did not have an evident effect on frequency and amplitude of s EPSCs and m EPSCs(p > 0.05).However,muscarine reduced evoked EPSCs in both types of interneurons,which was accompanied by increased changes in the paired-pulse ratio.Bath application of muscarine significantly reduced the frequency of m IPSCs and s IPSCs in SST interneurons(p < 0.01),but not in PV interneurons.Scopolamine significantly increased the frequency of m IPSCs and s IPSCs in SST interneurons(p < 0.05),but not in PV interneurons.Moreover,muscarine reduced evoked IPSCs in PV interneurons(p < 0.01),but not seen in SST interneurons.However,it was an increase in the paired-pulse ratio of evoked IPSCs in SST interneurons(p < 0.05),but not seen in PV interneurons.In forced swimming experiments,intraperitoneal injection of scopolamine significantly reduced immobilized behavior in adolescent and adult mice(p < 0.01).In addition,in immunofluorescence and electrophysiological experiments,we identified the morphological and electrophysiological characteristics of SST-cre/Ai9-RFP mice and PV-cre/Ai9-RFP mice expressing red fluorescent protein(RFP)in ACC brain regions of SST and PV interneurons.Conclusion: Current experimental results indicate that the activity of m ACh R facilitates the function of the excitatory synapses in both SST and PV interneurons in the ACC region,but attenuates the activity of the inhibitory synapses only in SST interneurons without significant effect on that in PV interneurons.Different types of interneurons may play different roles in the mechanism of rapid depression.However,Scopolamine’s rapid antidepressant effect through the m-type choline receptor of interneurons still needs to be further explored,so as to provide certain thinking and basis for drug development and treatment of depression.