5-羟色胺2C受体对形觉剥夺性成年弱视大鼠离体脑片初级视皮层长时程增强的影响
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摘要
目的探讨5-羟色胺2C受体(5-HT2CR)对形觉剥夺性成年弱视大鼠离体脑片视皮层V1M区长时程增强(LTP)的影响。方法将16只2周龄Spargue Dawley大鼠随机分为正常对照组和单眼形觉剥夺组,每组8只。正常对照组大鼠不做任何处理;单眼形觉剥夺组大鼠行右侧眼睑缝合术制备单眼形觉剥夺性弱视模型,造模成功后饲养6周,然后处死2组大鼠,冠状切取400μm厚视皮层脑组织切片并孵育于人工脑脊液中。根据人工脑脊液中加入的药物不同,将正常对照组大鼠视皮层切片作为A组,将剥夺眼对侧视皮层切片分为B、C、D和E组,将剥夺眼同侧视皮层切片分为F、G、H和I组。A、B、F组人工脑脊液中不加任何药物,C、G组加生理盐水,D、H组加10μmol·L-15-羟色胺盐酸盐,E、I组加10μmol·L-1SB 242084和10μmol·L-15-羟色胺盐酸盐。采用细胞外微电极记录法对各组大鼠视皮层组织切片进行电生理学实验,记录离体组织切片视皮层V1M区LTP并计算神经元场突触后电位(f PSP)斜率。结果 A、B、C、D、E、F、G、H、I组大鼠视皮层f PSP斜率分别为(198.1±13.5)%、(106.3±8.3)%、(106.3±8.3)%、(157.1±9.7)%、(102.6±4.7)%、(144.5±2.9)%、(144.5±2.9)%、(192.2±8.6)%和(129.7±13.5)%。A、B、F组大鼠视皮层f PSP斜率两两比较差异均有统计学意义(P<0.001),其中A组大鼠视皮层f PSP斜率高于B、F组(P<0.001),B组大鼠视皮层f PSP斜率低于F组(P<0.001)。D组大鼠视皮层f PSP斜率高于C组(t=-10.833,P<0.001);H组大鼠视皮层f PSP斜率高于D、G组(t=-6.841、-10.616,P<0.001);E组大鼠视皮层f PSP斜率低于D、I组(t=11.872、-3.910,P<0.001,P<0.05);I组大鼠视皮层f PSP斜率低于H组(t=9.911,P<0.001)。结论单眼形觉剥夺可造成双侧视皮层神经元功能减退,5-羟色胺盐酸盐可通过5-HT2CR起到一定逆转作用。
Objective To investigate the effects of 5-hydroxytryptamine-2 C subunit receptor(5-HT2 CR) on long-term potentiation(LTP) of V1 M region visual cortex of form deprivation adult amblyopia rats. Methods Sixteen two weeks old Spargue Dawley rats were randomly divided into normal control group and monocular form deprivation group,with 8 rats in each group. The rats in the normal control group were not given any intervention; the rats in the monocular form deprivation group were sutured the right eye lid to establish the monocular form deprivation amblyopia model. All rats were fed for 6 weeks after establishing the model successfully,then the rats in the two groups were sacrificed and the coronal examination of 400 μm thick cortical brain slices were incubated in artificial cerebrospinal fluid artificial cerebrospinal fluid(ACSF). According to the difference of drugs in ACSF,the visual cortex slices of rats in normal control group were selected as group A; the contralateral visual cortex slices of the deprivation eye were divided into group B,group C,group D and group E; the ipsilateral visual cortex slices of the deprivation eye were divided into group F,group G,groupH and group I. The ACSF of group A,B and F did not added any drugs; the ACSF of group C and group G were added with physiological saline; the ACSF of group D and groupH were added with 10 μmol · L-15-hydroxytryptamine hydrochloride; the ACSF of group E and group I were added with10 μmol·L-1 SB 242084 and 10 μmol·L-15-hydroxytryptamine hydrochloride. The electrophysiology experiment was performed in all of the visual cortex slices by extracellular microelectrode recording and the visual cortex fidd postsynaptic potential(f PSP) slope of V1 M region of the visual cortex was recorded. Results The f PSP in group A,B,C,D,E,F,G,H,I was(198. 1 ± 13. 5) %,(106. 3 ± 8. 3) %,(106. 3 ± 8. 3) %,(157. 1 ± 9. 7) %,(102. 6 ± 4. 7) %,(144. 5 ± 2. 9) %,(144. 5 ±2. 9) %,(192. 2 ± 8. 6) % and(129. 7 ± 13. 5) %,respectively. There was statistic difference in f PSP slope of visual cortex among the group A,B,F(P < 0. 001); the f PSP slope of visual cortex of rats in group A was significantly higher than that in the group B and group F(P < 0. 001); the f PSP slope of visual cortex of rats in group B was significantly lower than that in the group F(P < 0. 001). The f PSP slope of visual cortex in group D was significantly higher than that in the group C(t =-10. 833,P < 0. 001); the f PSP slope of visual cortex in groupH was significantly higher than that in the group D and group G(t =-6. 841,-10. 616; P < 0. 001). The f PSP slope of visual cortex in group E was significantly lower than that in the group D and group I(t = 11. 872,-3. 910; P < 0. 001,P < 0. 05); the f PSP slope of visual cortex in group I was significantly lower than that in the groupH(t = 9. 911,P < 0. 001). Conclusion Monocular deprivation can lead to the dysfunction of bilateral visual cortex neurons and 5-hydroxytryptamine hydrochloride can reverse this phenomenon through 5-HT2 CR.
Objective To investigate the effects of 5-hydroxytryptamine-2 C subunit receptor(5-HT2 CR) on long-term potentiation(LTP) of V1 M region visual cortex of form deprivation adult amblyopia rats. Methods Sixteen two weeks old Spargue Dawley rats were randomly divided into normal control group and monocular form deprivation group,with 8 rats in each group. The rats in the normal control group were not given any intervention; the rats in the monocular form deprivation group were sutured the right eye lid to establish the monocular form deprivation amblyopia model. All rats were fed for 6 weeks after establishing the model successfully,then the rats in the two groups were sacrificed and the coronal examination of 400 μm thick cortical brain slices were incubated in artificial cerebrospinal fluid artificial cerebrospinal fluid(ACSF). According to the difference of drugs in ACSF,the visual cortex slices of rats in normal control group were selected as group A; the contralateral visual cortex slices of the deprivation eye were divided into group B,group C,group D and group E; the ipsilateral visual cortex slices of the deprivation eye were divided into group F,group G,groupH and group I. The ACSF of group A,B and F did not added any drugs; the ACSF of group C and group G were added with physiological saline; the ACSF of group D and groupH were added with 10 μmol · L-15-hydroxytryptamine hydrochloride; the ACSF of group E and group I were added with10 μmol·L-1 SB 242084 and 10 μmol·L-15-hydroxytryptamine hydrochloride. The electrophysiology experiment was performed in all of the visual cortex slices by extracellular microelectrode recording and the visual cortex fidd postsynaptic potential(f PSP) slope of V1 M region of the visual cortex was recorded. Results The f PSP in group A,B,C,D,E,F,G,H,I was(198. 1 ± 13. 5) %,(106. 3 ± 8. 3) %,(106. 3 ± 8. 3) %,(157. 1 ± 9. 7) %,(102. 6 ± 4. 7) %,(144. 5 ± 2. 9) %,(144. 5 ±2. 9) %,(192. 2 ± 8. 6) % and(129. 7 ± 13. 5) %,respectively. There was statistic difference in f PSP slope of visual cortex among the group A,B,F(P < 0. 001); the f PSP slope of visual cortex of rats in group A was significantly higher than that in the group B and group F(P < 0. 001); the f PSP slope of visual cortex of rats in group B was significantly lower than that in the group F(P < 0. 001). The f PSP slope of visual cortex in group D was significantly higher than that in the group C(t =-10. 833,P < 0. 001); the f PSP slope of visual cortex in groupH was significantly higher than that in the group D and group G(t =-6. 841,-10. 616; P < 0. 001). The f PSP slope of visual cortex in group E was significantly lower than that in the group D and group I(t = 11. 872,-3. 910; P < 0. 001,P < 0. 05); the f PSP slope of visual cortex in group I was significantly lower than that in the groupH(t = 9. 911,P < 0. 001). Conclusion Monocular deprivation can lead to the dysfunction of bilateral visual cortex neurons and 5-hydroxytryptamine hydrochloride can reverse this phenomenon through 5-HT2 CR.
引文
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[15]BESSINIS D P,DALLA C,KOKRAS N,et al.Sex-dependent neurochemical effects of environmental enrichment in the visual system[J].Neuroscience,2013,254(19):130-140.
[16]JANG H J,CHO K H,JOO K,et al.Differential modulation of phasic and tonic inhibition underlies serotonergic suppression of long-term potentiation in the rat visual cortex[J].Neuroscience,2015,301(20):351-362.
[17]PAPADOPOULOS G C,PARNAVELAS J G,BUIJS R M.Light and electron microscopic immunocytochemical analysis of the serotonin innervation of the rat visual cortex[J].J Neurocytol,1987,16(6):883-892.
[18]蔺静静,刘向玲,王圆月,等.丰富环境及反转缝合治疗后突触素对关键期内视皮质神经元可塑性的影响[J].眼科新进展,2015,35(4):330-333.
[19]BARONCELLI L,SALE A,VIEGI A,et al.Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex[J].Exp Neurol,2010,226(1):100-109.
[20]PALACIOS J M.Serotonin receptors in brain revisited[J].Brain Res,2016,1645(15):46-49.
[2]BALOG J,MATTHIES U,NAUMANN L,et al.Social experience modulates ocular dominance plasticity differentially in adult male and female mice[J].Neuroimage,2014,103(2014):454-456.
[3]MAYA VETENCOURT J F,SALE A,VIEGI A,et al.The antidepressant fluoxetine restores plasticity in the adult visual cortex[J].Science,2008,320(5874):385-388.
[4]GAGOLEWICZ P J,DRINGENBERG H C.Age-dependent switch of the role of serotonergic 5-HT1A receptors in gating long-term potentiation in rat visual cortex in vivo[J].Neural Plast,2016,2016:1-11.
[5]刘虎,赵堪兴.斜视性弱视视皮层神经元时空特性的改变及其相关机制研究[D].天津:天津医科大学,2004.
[6]WANG J,ZHAO J,LIU Z,et al.Acute ethanol inhibition of gamma oscillations is mediated by Akt and GSK3β[J].Front Cell Neurosci,2016,10(17):1-12.
[7]张锐,刘向玲,路承彪,等.Ⅰ组代谢性谷氨酸受体在单眼形觉剥夺大鼠视皮层神经元突触传递效能中的作用[J].中华实验眼科杂志,2016,34(4):293-297.
[8]SUGIMURA T,YAMAMOTO M,YAMADA K,et al.Visual experience regulates the development of long-term synaptic modifications induced by low-frequency stimulation in mouse visual cortex[J].Neurosci Res,2017,102(17):36-44.
[9]LI D K,ZHANG C,GU Y,et al.The spatial-temporal interaction in the LTP induction between layerⅣto layerⅡ/Ⅲand layerⅡ/Ⅲto layerⅡ/Ⅲconnections in rats'visual cortex during the development[J].Neuroscience,2017,350(14):39-53.
[10]JEFFERIS J M,CONNOR A J,CLARKE M P.Amblyopia[J].BMJ,2015,351(12):h5811.
[11]PARK S W,JANG H J,CHO K H,et al.Developmental switch of the serotonergic role in the induction of synaptic long-term potentiation in the rat visual cortex[J].Korean J Physiol Pharmacol,2012,16(1):65-70.
[12]LIU H,LI Y,WANG Y,et al.The distinct role of NR2B subunit in the enhancement of visual plasticity in adulthood[J].Molecular Brain,2015,8(19):2-12.
[13]MAINARDI M,LANDI S,GIANFRANCESCHI L,et al.Environmental enrichment potentiates thalamocortical transmission and plasticity in the adult rat visual cortex[J].J Neurosci Res,2010,88(14):3048-3059.
[14]KIM H S,JANG H J,CHO K H,et al.Serotonin inhibits the induction of NMDA receptor-dependent long-term potentiation in the rat primary visual cortex[J].Brain Res,2006,1103(1):49-55.
[15]BESSINIS D P,DALLA C,KOKRAS N,et al.Sex-dependent neurochemical effects of environmental enrichment in the visual system[J].Neuroscience,2013,254(19):130-140.
[16]JANG H J,CHO K H,JOO K,et al.Differential modulation of phasic and tonic inhibition underlies serotonergic suppression of long-term potentiation in the rat visual cortex[J].Neuroscience,2015,301(20):351-362.
[17]PAPADOPOULOS G C,PARNAVELAS J G,BUIJS R M.Light and electron microscopic immunocytochemical analysis of the serotonin innervation of the rat visual cortex[J].J Neurocytol,1987,16(6):883-892.
[18]蔺静静,刘向玲,王圆月,等.丰富环境及反转缝合治疗后突触素对关键期内视皮质神经元可塑性的影响[J].眼科新进展,2015,35(4):330-333.
[19]BARONCELLI L,SALE A,VIEGI A,et al.Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex[J].Exp Neurol,2010,226(1):100-109.
[20]PALACIOS J M.Serotonin receptors in brain revisited[J].Brain Res,2016,1645(15):46-49.