| ?Objective?To investigate the neural connections between the ventral subiculum(vSub),entorhinal cortex(EC),and nucleus accumbens(NAC)and their roles in schizophreniform sensorimotor gating dysfunction.?Methods?(1)The neural connections between vSub,EC,and NAC were labeled by retrograde tracing of cholera toxin B subunit(CTB),and the excitatory neuron marker CaMKII? and inhibitory neuron marker GAD67 were qualitatively detected by immunostaining.(2)Brain stereotaxic injection of viruses carrying photosensitive genes and embedding optical fibers to construct optogenetic control models to specifically activate a single neural circuit.Changes in 'photo stimulation-behavioral function' were tested by prepulse inhibition experiment and open field experiment.(3)Animal models of schizophrenia-like sensorimotor gating disorder were modeled in chronic way or acute way.Chronic sensorimotor gating function injury models were constructed by injecting 0.2 mg/kg MK-801 into the back of the neck of pups 8-21 days after birth.Aute models were constructed by 0.5 mg/kg MK-801 intraperitoneally into adults 30 min before behavioral experiments,and prepulse inhibition experiment,open field experiment,and elevated plus maze experiment were performed model verification.(4)Functional changes in related circuits in schizophrenia-like sensorimotor gating disorder were examined by CTB retrograde tracing combined with c-Fos immunostaining,and whether disruption of sensorimotor gating could be improved by injection of muscimol into the vSub.?Results?(1)Direct excitatory glutamatergic projections from the lateral entorhinal cortex(LEC)to the vSub,nucleus accumbens shell(NAC Shell)and nucleus accumbens core(NAC Core)were found;only direct excitatory glutamatergic projections from the medial entorhinal cortex(MEC)to the vSub and NAC Shell were present.(2)In the prepulse inhibition experiment,only when the excitatory projection from the LEC to the vSub was activated by 473 nm laser,the prepulse inhibition rate of rats showed a decrease compared with the control group(P<0.05),while the startle reflex amplitude did not change significantly compared with the control group(P>0.05).In the open field experiment,only when the excitatory projection of MEC to vSub was activated by 473 nm laser,the distance moved of rats increased(P<0.05)and the velocity increased(P<0.05)compared with the control group.(3)When MK-801 was chronically modeled,the change in the prepulse inhibition rate in rats was not statistically significant compared with the control group(P>0.05),and the startle reflex amplitude increased compared with the control group(P<0.001);the distance moved in the open field increased compared with the control group(P<0.001),and the duration in the central arena was prolonged compared with the control group(P<0.001);the percentage of duration in the open arm of the maze increased compared with the control group(P<0.05).During acute modeling,the prepulse inhibition rate in rats decreased compared with the control group(P<0.001),the startle reflex amplitude increased compared with the control group(P<0.01);the distance moved in the open field increased compared with the control group(P<0.01).These results indicate that acute intraperitoneal injection of MK-801 can induce schizophrenia-like animal behavioral models.(4)When sensorimotor gating was impaired induced by MK-801,c-Fos expression in excitatory projection neurons from LEC to vSub was increased compared with the control group(P<0.05),and after inhibition of vSub activity,the inhibition rate of prepulse in rats was increased compared with the control group(P<0.05),and the change in startle reflex amplitude was not statistically significant compared with the control group(P>0.05).?Conclusions?(1)Excitatory projections from the LEC to the vSub are involved in the regulation of sensorimotor gating,and excessive activation could lead to impaired sensorimotor gatingfunction.(2)When sensorimotor gating is disrupted,inhibition of vSub activity helps to recover impaired function. |
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