HYPERPOLARIZING AND DEPOLARIZING GABA-A RECEPTOR-MEDIATED DENDRITIC INHIBITION IN AREA CA1 OF THE RAT HIPPOCAMPUS
HYPERPOLARIZING AND DEPOLARIZING GABA-A RECEPTOR-MEDIATED DENDRITIC INHIBITION IN AREA CA1 OF THE RAT HIPPOCAMPUS
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DOI：
10.1152/jn.1991.66.5.1538
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发表时间：
1991-11-01
影响因子：
2.5
通讯作者：
TEYLER, TJ
中科院分区：
文献类型：
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作者：
LAMBERT, NA;BORRONI, AM;TEYLER, TJ
1.采用细胞内、细胞外记录和一维电流源密度（CSD）分析方法，研究了大鼠海马脑片CA 1区GABA（A）受体介导的锥体神经元树突抑制.电刺激Schaffer侧支/连合纤维诱发单突触兴奋性突触后电位（EPSP）和群体EPSP，随后是双相抑制性突触后电位（IPSP）。在兴奋性氨基酸受体拮抗剂6，7-二硝基喹喔啉-2，3-二酮（DNQX）和D，L-2-氨基-5-膦酰基戊酸（APV）存在下，刺激辐射层可诱发GABA（A）和GABA（B）受体或其介导的单突触IPSPs和快、迟正场电位。辐射。在DNQX和APV存在下诱发的快速单突触IPSP和快速正场电位被GABA（A）受体拮抗剂甲碘荷包牡丹碱（BMI; 30 μ M）可逆地消除，并且不被GABA（B）受体拮抗剂P-[3-氨基丙基]-P-二乙氧基甲基次膦酸（CGP 35 348; 0.1-1.0 mM）改变。CGP 35 - 348（0.1 mM）可逆地阻断晚期单突触IPSP和晚期正场电位。这些结果表明，快场电位是GABA（A）受体介导的群体IPSPs（GABA（A），fastpIPSPs），晚场电位是GABA（B）受体介导的群体IPSPs（GABA（B），latepIPSPs）.当细胞外Cl-浓度（[Cl-1]o）从132 mM降低至26 mM时，快速pIPSP可逆性消失，同时快速IPSP的逆转电位发生去极化转变。成对或重复刺激。辐射状蛋白可逆地抑制快pIPSP和快IPSP。快速pIPSPs的配对脉冲抑制被CGP 35 348可逆地拮抗（0.40。8 mM）。S的层流分析放射诱发的快速pIPSP和一维CSD分析揭示了s.辐射和被动电流在s中下沉。奥里恩斯和南分子陷窝S.放射源被BMI的压力消除。radiatum，而不是s。东方人刺激在s。奥里恩斯山或S。陷窝分子诱发GABA（A）电流源水平的刺激部位。抑制性电流在树突上的位置随刺激位置的变化而变化，从而改变了兴奋性电流的分布.在存在4-氨基吡啶（50-100 μ M）的情况下，DNQX和APV自发发生或可诱发持久去极化GABA（A）受体介导的反应（LLD）。与% s关联的电流汇。放射诱发的LLDs位于与超极化快速IPSPs相关的源相同的树突区域。这些结果表明，位于锥体神经元顶树突和基底树突上的GABA（A）受体激活产生外向Cl-1电流和超极化IPSP。这表明，去极化反应的树突状GABA的应用和顺向激活区CA 1不导致内向氯电流。
1. Gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis.2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABA(A) and late, GABA(B) receptor or-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum.3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABA(A) receptor antagonist bicuculline methiodide (BMI; 30-mu-M) and were not changed by the GABA(B) receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35 348; 0.1-1.0 mM). CGP 35 348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABA(A) receptor-mediated population IPSPs (GABA(A), fast pIPSPs) and that late field potentials are GABA(B) receptor-mediated population IPSPs (GABA(B), late pIPSPs).4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration ([Cl-1]o) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35 348 (0.40. 8 mM).5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABA(A) current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current.6. In the presence of 4-aminopyridine (50-100-mu-M), DNQX and APV long-lasting depolarizing GABA(A) receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs.7. These results suggest that activation of GABA(A) receptors located on pyramidal neuron apical and basal dendrites produces outward Cl-1 current and hyperpolarizing IPSPs. This suggests that depolarizing responses to dendritic GABA application and orthodromic activation in area CA1 do not result from inward chloride current.