Baclofen对大鼠脊髓薄片胶状质神经元的抑制作用

用脊髓薄片全细胞电压钳法观察激活γ－氨基丁酸Ｂ亚型受体（ＧＡＢＡＢR)对大鼠脊髓背角胶状质（ＳＧ）神经元活动的影响,选择性ＧＡＢＡＢＲ激动剂baclofen减少所有被记录ＳＧ神经元（n＝１５）的微小兴奋性突触后电流（mEPSGs）的发放频率。同时引起一缓慢的抑制性（外向）膜电流并伴有膜电导增加,细胞内电泳Ｇ蛋白偶联受体抑制剂（ＧＤＰ－β－Ｓ）抑制被钳制神经元的Ｇ蛋白偶联受体后,baclofen引起的缓慢外向电流被抑制,但对mEPSC频率的减低作用依然存在。结果提示脊髓内baclofen敏感的ＧＡＢＡＢ受体被激活后直接引起ＳＧ神经元超极化并能减少突触前递质的释放。     

生长抑素调节疑核神经元兴奋性氨基酸受体介导的兴奋

在含有孤束核中央亚核（ＮＴＳｃ）疑核神经元密集区（ＡＭＢｃ）及孤束─疑核传导束的脑片，注射生长抑素（ＳＳＴ）于ＡＭＢｃ区，对Ｎ—ｍｅｔｈｙｌ—Ｄ－ａｓｐａｒｔａｔｅ（ＮＭＤＡ）引起的疑核神经元膜电位去极化有易化作用，而注射ｃｙｓｔｅａｍｉｎｅ耗竭内源性ＳＳＴ后，ＮＭＤＡ的去极化作用减弱；ＮＭＤＡ受体阻断剂Ｄ，Ｌ—２—ａｍｉｎｏ—７一ｐｂｏｓｐｈｏ－ｎｏｈｅｐｔａｎｏｉｃａｃｉｄ（ＡＰ─７）使疑核神经元兴奋性突触后电位（ＥＰＳＰ）幅度降低，而ＳＳＴ可翻转ＡＰ—７的抑制效应；对ｎｏｎ—ＮＭＤＡ介导的疑核神经元膜去极化，ｃｙｓｔｅａｍｉｎｅ亦对其有明显抑制作用；甘氨酸（ｇｌｙｃｉｎｅ）可阻断ＳＳＴ易化疑核神经元的去极化作用。这些结果表明，ＳＳＴ对疑核神经元兴富性氨基酸（ＥＡＡ）受体介导的兴奋起重要的调节作用。     

P物质对大鼠新鲜分离DRG神经元NMDA及GABA激活电流的调制作用

实验应用全细胞膜片钳技术在大鼠新鲜分离的背根神经节（ＤＲＧ）神经元胞体膜上观察到Ｐ物质（ＳＰ）对ＮＭＤＡ和ＧＡＢＡ激活电流有调制作用。单独给予ＳＰ（１０－８～１０－６ｍｏｌ／Ｌ）可在ＤＲＧ神经元记录到一幅值较小的，浓度依赖性的无明显去敏感之内向电流。预加ＳＰ３０ｓ后，其对ＮＭＤＡ和ＧＡＢＡ激活电流分别具有明显的增强和抑制作用，而且ＳＰ对ＮＭＤＡ和ＧＡＢＡ激活电流的增强和抑制作用也是剂量依赖性的。如ＳＰ浓度为１０－７ｍｏｌ／Ｌ时，可使ＮＭＤＡ激活电流较之对照增强４６．３±７．２％（ｘ±ｓ，ｎ＝８）；使ＧＡＢＡ激活电流比对照减小３８．９±７．８％（ｘ±ｓ，ｎ＝６）．ＳＰ的此种调制作用可以在同一ＤＲＧ神经元上观察到。     

背根神经节神经元胞体膜可能存在NMDA自身受体

应用经酶和机械消化分离的大鼠背根神经节（ＤＲＧ）神经元进行实验。首先运用全细胞膜片箝技术找到ＮＭＤＡ可引起一内向电流的神经元,此内向电流可被甘氨酸明显增强,并被ＮＭＤＡ受体的特异性拮抗剂ＡＰＶ完全阻断。随后,把经电生理技术证实膜上存在ＮＭＤＡ受体的这一ＤＲＧ神经元用微吸管转移到载玻片上,进行谷氨酸神经递质免疫组织化学检测。１０／１８的ＤＲＧ细胞呈免疫反应阳性,结果为ＤＲＧ神经元膜上存在ＮＭＤＡ自身受体提供了新证据。     

突触前nACh受体对成年爪蟾视顶盖区微突触后电流的调制作用

采用全细胞膜片钳方法,研究了尼古丁乙酰胆碱受体（nACh）对成年非洲爪瞻（Xenopus)脑片视顶盖区自发微突触后电流(mPSC)的调制作用。在顶盖区第六层细胞上,记录到自发微抑制性突触后电流（mIPSC)成分,观察到其发放频率明显高于自发微兴奋性突触后电流（mEPSC)的频率。在TTX和atopine存在的情况下,cabachol等nACh的激动剂可使mPSC的频率增加,但振幅不受影响。nAChR的竞争性拮抗剂DH－β-E可抑制由于加入nAChR激动剂所引起的频率增加,而对nAChR亚单位的选择性阻断剂mecamylamine,则仅能在个别细胞上发挥这一作用。     

重症肌无力患者神经肌肉接头处的超微结构研究

目的探讨重症肌无力（ＭＧ）时神经肌肉接头（ＮＭＪ）突触后、前膜的变化及其意义。方法肋间内肌在辣根过氧化酶标记的α银环蛇毒素（ＨＲＰαＢｕＴｘ）标记后，用图形扫描及医学图像分析软件测量电镜照片中ＮＭＪ的各项指标，并与对照组比较分析。结果ＭＧ时突触后膜长度缩短，后、前膜长度比值变小，神经末端面积及其与突触后膜面积之比变小，突触后膜上的乙酰胆碱受体（ＡＣｈＲ）减少了３５．９％。结论ＭＧ时ＮＭＪ的变化主要存在于突触后膜。突触后、前膜长度之比对本病的诊断更有临床意义。     

幼年非洲爪蟾视顶盖区突触前、后膜上受体间的相互作用

目的　 记录幼年非洲爪蟾视顶盖区第六层神经元的自发性微突触后电流 (mPSCs)。 方法 　应用盲法电压膜片钳全细胞记录技术。 结果　 观察到用谷氨酸受体激动剂NMDA灌流脑片后先引起mIPSCs的频率明显增加并出现内向膜电流及高频的mEPSCs,经一段时间洗脱后mIPSCs和mEPSCs又均完全消失 ,而膜电流恢复到原来未加NMDA前的水平。GABA受体的激动剂GABA可诱发明显的外向膜电流。GABAa受体拮抗剂荷包牡丹碱 (bicucullin ,BM)不仅能将mIPSCs全部抑制掉 ,并且还可以诱发mEPSCs。谷氨酸受体的拮抗剂APV对mPSCs亦有类似的作用 ,不仅可以抑制顶盖神经元的mEPSCs,而且可以使原有的mIPSCs的频率和振幅均增加。 结论　幼年期的突触前、后膜上既有兴奋性谷氨酸能受体也有抑制性γ 氨基丁酸能受体 ,而且在突触前膜上受体可以调制突触末梢神经递质的释放。因此突触前、后膜上的受体间存在相互作用 ,以确保突触前后活动和功能上的稳定 ,从而达到神经网络的平衡。     

P物质和谷氨酸介导辣椒素引起的脊髓γ—氨基丁酸的释放

以前的实验证明辣椒素急性处理外周神经可导致初级传入末梢大量释放Ｐ物质，同时也观察到脊髓背角浅层ＧＡＢＡ的排空。本研究的目的在于探讨外周施加辣椒素激活背角ＧＡＢＡ能神经元，是否与初级传入末梢释放的递质有关。结果表明，外周胫神经辣椒素处理３０分钟即可引起的同侧背角浅层ＧＡＢＡ免疫反应产物（ＧＡＢＡ—ＩＲ）的明显减少，予先用ＮＫ—１受体桔抗剂Ｓｐａｎｔｉｄｅ（５０ｎＭ）或ＮＭＤＡ受体拮抗剂ＡＰＶ（１００μＭ）灌流脊髓腰膨大表面，可部分阻断辣椒素引起的ＧＡＢＡ—ＩＲ密度和ＧＡＢＡ—ＩＲ阳性神经元数目的减少，使ＧＡＢＡ—ＩＲ有不同程度的恢复。本文讨论了初级传入末梢释放的Ｐ物质和兴奋性氨基酸与ＧＡＢＡ能神经元在脊髓痛觉信息调制中的作用。     

突触前NMDA受体,还是突触束泡连接蛋白?

突触前ＮＭＤＡ受体，还是突触束泡连接蛋白？Ｓｍｉｒｎｏｖｎ等用抗谷氨酸结合蛋白抗体突触束泡连接蛋白ｓｙｎｔｕｘｉｎ相同。然而，ＧＲ３３－ｍＲＮＡ在爪蟾卵母细胞表达时却产生一种谷氨酸受体，其药理学特征类似与突触后ＮＭＤＡ受体，电生理学特性则明显不同。作...     

N－甲基－D－天门冬氨酸受体拮抗剂对猫创伤性脑水肿的影响

本实验观察了竞争性Ｎ－甲基－Ｄ－天门冬氨酸（ＮＭＤＡ）受体拮抗剂Ｄ－（－）－２－氨基－７－磷庚酸酯（Ｄ－ＡＰ７）对猫创伤性脑水肿的影响。结果发现Ｄ－ＡＰ７可明显减轻脑含水量，改善脑Ｎａ＋、Ｋ＋、ｃａ＋＋、Ｍｇ＋＋含量，提示兴奋性氨基酸与创伤性脑水肿有关，其中ＮＭＤＡ受体可能起主要作用，本文探讨了ＮＭＤＡ受体拮抗剂对创伤性脑水肿的保护机理。     

Selective 5-HT receptor inhibition of glutamatergic and GABAergic synaptic activity in the rat dorsal and median raphe

The dorsal (DR) and median (MR) raphe nuclei contain 5-hydroxytryptamine (5-HT) cell bodies that give rise to the majority of the ascending 5-HT projections to the forebrain. The DR and MR have differential roles in mediating stress, anxiety and depression. Glutamate and GABA activity sculpt putative 5-HT neuronal firing and 5-HT release in a seemingly differential manner in the MR and DR, yet isolated glutamate and GABA activity within the DR and MR has not been systematically characterized. Visualized whole-cell voltage-clamp techniques were used to record excitatory and inhibitory postsynaptic currents (EPSC and IPSC) in 5-HT-containing neurons. There was a regional variation in action potential-dependent (spontaneous) and basal [miniature (m)] glutamate and GABAergic activity. mEPSC activity was greater than mIPSC activity in the DR, whereas in the MR the mIPSC activity was greater. These differences in EPSC and IPSC frequency indicate that glutamatergic and GABAergic input have distinct cytoarchitectures in the DR and MR. 5-HT(1B) receptor activation decreased mEPSC frequency in the DR and the MR, but selectively inhibited mIPSC activity only in the MR. This finding, in concert with its previously described function as an autoreceptor, suggests that 5-HT(1B) receptors influence the ascending 5-HT system through multiple mechanisms. The disparity in organization and integration of glutamatergic and GABAergic input to DR and MR neurons and their regulation by 5-HT(1B) receptors may contribute to the distinction in MR and DR regulation of forebrain regions and their differential function in the aetiology and pharmacological treatment of psychiatric disease states.     

GABAA receptors facilitate spontaneous glutamate release in rat periaqueductal gray neurons

The functional role of presynaptic γ-aminobutyric acid (GABA)(A) receptors in excitatory glutamatergic transmission was examined in rat periaqueductal gray neurons recorded using a conventional whole-cell patch clamp technique. Muscimol, a GABA(A) receptor agonist, significantly increased the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, and this effect was completely blocked by the selective GABA(A) receptor antagonist. The muscimol-induced facilitation of spontaneous excitatory postsynaptic current frequency disappeared either in the presence of tetrodotoxin or Cd. The results suggest that the activation of presynaptic GABA(A) receptors directly depolarizes glutamatergic terminals resulting in the facilitation of spontaneous glutamate release, and that presynaptic GABA(A) receptors play an important role in the regulation of various physiological functions mediated by the periaqueductal gray.     

Increased Kv1 channel expression may contribute to decreased sIPSC frequency following chronic inhibition of NR2B-containing NMDAR

Numerous studies have documented the effects of chronic N-methyl-D-aspartate receptor (NMDAR) blockade on excitatory circuits, but the effects on inhibitory circuitry are not well studied. NR2A- and NR2B-containing NMDARs play differential roles in physiological processes, but the consequences of chronic NR2A- or NR2B-containing NMDAR inhibition on glutamatergic and GABAergic neurotransmission are unknown. We investigated altered GABAergic neurotransmission in dentate granule cells and interneurons following chronic treatment with the NR2B-selective antagonist, Ro25,6981, the NR2A-prefering antagonist, NVP-AAM077, or the non-subunit-selective NMDAR antagonist, D-APV, in organotypic hippocampal slice cultures. Electrophysiological recordings revealed large reductions in spontaneous inhibitory postsynaptic current (sIPSC) frequency in both granule cells and interneurons following chronic Ro25,6981 treatment, which was associated with minimally altered sIPSC amplitude, miniature inhibitory postsynaptic current (mIPSC) frequency, and mIPSC amplitude, suggesting diminished action potential-dependent GABA release. Chronic NVP-AAM077 or D-APV treatment had little effect on these measures. Reduced sIPSC frequency did not arise from downregulated GABA(A)R, altered excitatory or inhibitory drive to interneurons, altered interneuron membrane properties, increased failure rate, decreased action potential-dependent release probability, or mGluR/GABA(B) receptor modulation of GABA release. However, chronic Ro25,6981-mediated reductions in sIPSC frequency were occluded by the K+ channel blockers, dendrotoxin, margatoxin, and agitoxin, but not dendrotoxin-K or XE991. Immunohistochemistry also showed increased Kv1.2, Kv1.3, and Kv1.6 in the dentate molecular layer following chronic Ro25,6981 treatment. Our findings suggest that increased Kv1 channel expression/function contributed to diminished action potential-dependent GABA release following chronic NR2B-containing NMDAR inhibition and that these Kv1 channels may be heteromeric complexes containing Kv1.2, Kv1.3, and Kv1.6.     

L-phenylalanine selectively depresses currents at glutamatergic excitatory synapses

To explore the hypothesis that L-phenylalanine (L-Phe) depresses glutamatergic synaptic transmission and thus contributes to brain dysfunction in phenylketonuria (PKU), the effects of L-Phe on spontaneous and miniature excitatory postsynaptic currents (s/mEPSCs) in rat and mouse hippocampal and cerebrocortical cultured neurons were studied using the patch-clamp technique. L-Phe depressed the amplitude and frequency of both N-methyl-D-aspartate (NMDA) and non-NMDA components of glutamate receptor (GluR) s/mEPSCs. The IC(50) of L-Phe to inhibit non-NMDAR mEPSC frequency was 0.98 +/- 0.13 mM, a brain concentration seen in classical PKU. In contrast, D-Phe had a significantly smaller effect, whereas L-leucine, an amino acid that competes with L-Phe for brain transporter, had no effect on mEPSCs. Unlike GluR s/mEPSCs, GABA receptor mIPSCs were not attenuated by L-Phe. A high extracellular concentration of glycine prevented the attenuation by L-Phe of NMDAR current, activated by exogenous agonist, and of NMDAR s/mEPSC amplitude, but not of NMDAR s/mEPSC frequency. On the other hand, L-Phe significantly depressed non-NMDAR current activated by low but not high concentrations of exogenous agonists. Glycine-independent attenuation of NMDAR s/mEPSC frequency suggests decreased presynaptic glutamate release caused by L-Phe, whereas decreased amplitudes of NMDAR and non-NMDAR s/mEPSCs are consistent with competition of L-Phe for the glycine- and glutamate-binding sites of NMDARs and non-NMDARs, respectively. The finding that GluR activity is significantly depressed at conditions characteristic of classical PKU indicates a potentially important contribution of impaired GluR function to PKU-related mental retardation and provides important insights into the potential physiological consequences of impaired GluR function.     

Spontaneous and synaptic input from granule cells and the perforant path to dentate basket cells in the rat hippocampus

To characterize excitatory inputs to dentate basket cells from dentate granule cells and the perforant path, the whole-cell recording technique was used in neonatal rat hippocampal slices. Spontaneous excitatory input to basket cells was also examined and compared to that of other interneurons in the dentate gyrus. Basket cells were separable from other neurons in the dentate gyrus based on morphology and location, as determined by biocytin staining following recording, and by resting membrane potential, propensity to fire action potentials spontaneously, and miniature excitatory postsynaptic current (EPSC) characteristics. Minimal electrical stimulation of the granule cell layer evoked in basket cells short latency EPSCs that were composed of both N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) components as judged by their time course, voltage dependence, and blockade by selective antagonists. Perforant path EPSCs exhibited slower kinetics than EPSCs evoked by granule cell stimulation. Like granule cell evoked EPSCs, however, perforant path EPSCs were composed of both NMDA and AMPA components. Minimal electrical stimulation of the granule cell layer and perforant path evoked monosynaptic EPSCs in only 67% and 62% of the trials, respectively, suggesting that these inputs are as unreliable as previously determined inputs from CA3 pyramidal cells (48%). Tetrodotoxin-insensitive spontaneous miniature EPSCs were frequent in basket cells and non-basket interneurons residing either at the border between the granule cell layer and the hilus or deep within the hilus. Miniature EPSCs recorded from all cells held at ?70 mV were blocked completely by 3 μSM 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX). Though a component of the miniature EPSCs recorded from border and deep hilar interneurons at +40 mV was blocked by the NMDA receptor antagonist D -2-amino-phosphonovaleric acid (D-APV), miniature EPSCs in basket cells were insensitive to D-APV. We conclude that input from granule cells and the perforant path results in activation of basket cells via glutamatergic synapses that employ both NMDA and AMPA receptors. These inputs to basket cells likely contribute to feedback and feedforward inhibition of granule cells. The absence of an NMDA receptor component in spontaneous miniature EPSCs of dentate basket cells implies a difference in organization of excitatory synapses made onto basket cells compared with other hilar interneurons. © 1995 Wiley-Liss, Inc.     

BDNF‐induced endocannabinoid release modulates neocortical glutamatergic neurotransmission

Endocannabinoids (eCBs) and neurotrophins, particularly brain‐derived neurotrophic factor (BDNF), are potent neuromodulators found throughout the mammalian neocortex. Both eCBs and BDNF play critical roles in many behavioral and neurophysiological processes and are targets for the development of novel therapeutics. The effects of eCBs and BDNF are primarily mediated by the type 1 cannabinoid (CB1) receptor and the trkB tyrosine kinase receptor, respectively. Our laboratory and others have previously established that BDNF potentiates excitatory transmission by enhancing presynaptic glutamate release and modulating NMDA receptors. In contrast, we have shown that BDNF attenuates inhibitory transmission by inducing postsynaptic release of eCBs that act retrogradely to suppress GABA release in layer 2/3 of somatosensory cortex. Here, we hypothesized that BDNF also induces release of eCBs at excitatory synapses, which could have a mitigating or opposing effect on the direct presynaptic effects of BDNF. We found the highest levels of expression of CB1 and trkB and receptors in layers 2/3 and 5. Surprisingly, BDNF did not increase the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs) onto layer 5 pyramidal neurons in somatosensory cortex, in contrast to its effects in the hippocampus and visual cortex. However, the effect of BDNF on mEPSC frequency in somatosensory cortex was unmasked by blocking CB1 receptors or disrupting eCB release. Thus, BDNF‐trKB signaling regulates glutamate release in the somatosensory cortex via opposing effects, a direct presynaptic enhancement of release probability, and simultaneous postsynaptically‐induced eCB release that decreases release probability via presynaptic CB1 receptors.     

Muscarinic Inhibition of Glutamatergic Transmission onto Rat Magnocellular Basal Forebrain Neurons in a Thin-slice Preparation

We have examined excitatory and inhibitory transmission in visually identified rat magnocellular basal forebrain neurons using whole-cell patch-clamp recordings in a thin-slice preparation of the rat brain. In most cells, spontaneous excitatory and inhibitory synaptic activities could be recorded from their resting membrane potential. Following focal stimulation within the basal forebrain nucleus or directly onto visualized neighbouring neurons, postsynaptic currents were elicited in magnocellular basal forebrain cells held at -70 mV (a value close to their resting membrane potential). The synaptic responses were complex, consisting either mainly of excitatory postsynaptic currents (EPSCs), or inhibitory postsynaptic currents (IPSCs), or an EPSC-IPSC sequence. The EPSC component was consistent with the activation of AMPA/KA receptors, as it could be selectively blocked by CNQX. The IPSC component resulted in the activation of GABA_A receptors, and could be blocked by bicuculline. Since GABA-mediated transmissions were not frequently recorded, we focused on the glutamate-mediated transmission. Studies using specific calcium channel blockers suggested that both ω-conotoxin GVIA-sensitive and ω-agatoxin VIA-sensitive calcium channels contribute to the glutamatergic transmission onto magnocellular basal forebrain neurons. Carbachol (0.3–30 μM) had no observable effect on holding current, but produced a dose-dependent inhibition of the amplitude of evoked EPSCs. This cholinergic modulation was mediated by muscarinic receptors, as it could be antagonized by atropine. The inhibitory effect of carbachol on the amplitude of EPSCs could be significantly antagonized by 100 nM methoctramine, an M₂-receptor antagonist. In contrast, only a small degree of antagonism could be obtained with pirenzepine, an M₁-muscarinic receptor antagonist, when present at relatively high concentration of 1 μM. Moreover, the action of carbachol was presynaptic, since the frequency of miniature postsynaptic currents was reduced without affecting their amplitude. In conclusion, the present findings indicate that glutamate-mediated transmission onto magnocellular basal forebrain neurons appeared to involve both N- and P/Q-type calcium channels, and that muscarinic modulation of glutamatergic transmission to MBF neurons is mediated by a presynaptic M₂-muscarinic receptor subtypes.     

Involvement of prolactin, vasopressin and opioids in post-ictal antinociception induced by electroshock in rats

The local and endogenous nicotinic neuronal transmissions of dopaminergic neurons in the substantia nigra were confirmed electrophysiologically using a slice-patch technique. After identifying dopaminergic neurons based on their electrophysiological characteristics, miniature postsynaptic inward currents were recorded in the presence of atropine (a muscarinic acetylcholine receptor antagonist), bicuculline (a GABA receptor antagonist) and L-glutamic acid diethyl ester (GDEE) (a non-selective glutamate receptor antagonist). Under conditions that eliminated muscarinic, GABAergic and glutamatergic synaptic transmissions, we found miniature currents that were inhibited by the specific neuronal nicotinic receptor antagonists, dihydro-beta-erythroidine (DHbetaE) and/or methyllycaconitine (MLA) (selective alpha4beta2 and/or alpha7 nicotinic acetylcholine receptor antagonists, respectively). Under the same extracellular conditions, local stimulations in the vicinity of a target neuron evoked excitatory postsynaptic inward currents (EPSCs). These EPSCs were elicited in an extracellular Ca(2+) dependent manner and were also blocked by DHbetaE and/or MLA. These results suggest that dopaminergic neurons in the substantia nigra receive excitatory cholinergic inputs that are mediated via at least two types of postsynaptic nicotinic receptors, namely alpha7 and alpha4beta2 subtypes.     

Presynaptic and postsynaptic modulation of glutamatergic synaptic transmission by activation of α1‐ and β‐adrenoceptors in layer V pyramidal neurons of rat cerebral cortex

Adrenergic agonists have different modulatory effects on excitatory synaptic transmission depending on the receptor subtypes involved. The present study examined the loci of α₁‐ and β‐adrenoceptor agonists, which have opposite effects on excitatory neural transmission, involved in modulation of glutamatergic transmission in layer V pyramidal cells of rat cerebral cortex. Phenylephrine, an α₁‐adrenoceptor agonist, suppressed the amplitude of AMPA receptor‐mediated excitatory postsynaptic currents evoked by repetitive electrical stimulation (eEPSCs, 10 pulses at 33 Hz). The coefficient of variation (CV) of the 1st eEPSC amplitude and paired‐pulse ratio (PPR), which were sensitive to extracellular Ca²⁺ concentration, were not affected by phenylephrine. Phenylephrine suppressed miniature EPSC (mEPSC) amplitude without changing its frequency. In contrast, isoproterenol, a β‐adrenoceptor agonist, strongly increased the amplitude of the 1st eEPSC compared with that of the 2nd to 10th eEPSCs, which resulted in a decrease in PPR. Isoproterenol‐induced enhancement of eEPSC amplitude was accompanied by a decrease in CV. Isoproterenol increased the frequency of mEPSCs without significant effect on amplitude. Phenylephrine suppressed inward currents evoked by puff application of glutamate, AMPA, or NMDA, whereas isoproterenol application was not accompanied by significant changes in these inward currents. These findings suggest that phenylephrine decreases eEPSCs through postsynaptic AMPA or NMDA receptors, while the effects of isoproterenol are mediated by facilitation of glutamate release from presynaptic terminals without effect on postsynaptic glutamate receptors. These two different mechanisms of modulation of excitatory synaptic transmission may improve the “signal‐to‐noise ratio” in cerebral cortex. Synapse 63:269–281, 2009. © 2008 Wiley‐Liss, Inc.