胼胝体输入对猫17/18区交界神经元反应强度的影响

用微机控制的以一定速度移动的亮棒或暗棒作为视觉刺激,在视皮层一侧施加GABA或其拮抗剂荷苞牡丹碱(Bicuculline,简写为Bicu),在对侧皮层17/18区交界附近记录加药前后单细胞的视觉反应.结果表明,对侧施加GABA后有52.1%细胞反应减少,22.5%细胞反应增加;对侧施加Bicu后有44.9%细胞反应增加,23.2%细胞反应减少;对两种药物均无反应的细胞不足10%.实验中受胼胝体神经元影响的对侧细胞的百分比明显高于以往用其它方法所得到的结果.本文对实验结果的可靠性和意义做了讨论.     

在一侧视皮层施加GABA或其拮抗剂对另一侧神经元电诱发反应的影响

电刺激对侧皮层所驱动的神经元的反应多数因刺激侧施加GABA或其拮抗剂荷包牡丹碱(Bicu)而改变.反应的变化可以表现在:(a)反应潜伏期的变化,(b)反应峰(最大频率)的前移或滞后,(c)反应峰值的变化,(d)反应总脉冲数的改变等.以反应的最高频率和总脉冲数之积作为反应强度的指标,则在多数情况下(72.2%)GABA使反应减弱,它使6.7%的反应加强,其余的反应不受影响,Bicu使半数反应加强,使16.7%的反应减弱,其余的反应不受影响.     

大鼠中缝背核内γ-氨基丁酸加强针刺镇痛作用

本实验中,将γ-氨基丁酸(GABA)的受体激动剂异鹅羔胺(Mus)、受体拮抗剂荷苞牡丹碱(Bicu)、神经元摄取的阻断剂哌啶酸(Nip)和GABA合成酶抑制剂3-巯基丙酸(3-MPA)经埋植的引导管注入大鼠中缝背核,注射剂量均为 4μg/μl;并观察了上述注药对动物痛阈和针刺镇痛效应的影响。 脑内注射Mus和Nip 均能明显提高动物的痛阈( 20％— 40％,P<0.05和P<0.01)和加强针刺镇痛作用;这种增强作用至少能维持2h。脑内注射Bicu和3-MPA均不影响动物的痛阈(P>0.05),但是它们都能明显地降低针刺镇痛效应(P<0.05和P<0.01)。以上结果表明,中缝背核内的GABA递质在针刺镇痛中起着一定作用。     

胼胝体输入对猫皮层17/18交界区细胞方向和取向选择性的影响

用抑制性神经递质GABA阻断胼胝体输入、用微机控制的运动光棒作为视觉刺激,用金属电极胞外记录技术,研究猫皮层17/18区交界附近细胞方向选择性和取向选择性的变化.在被检测的48个细胞中,50%细胞的方向选择性强度,54.2%细胞的取向选择性强度发生了改变;约20%细胞的最优反应方向或.及最优取向发生了10-30°的偏移;共有56.2%细胞的方向选择性、58.3%细胞的取向选择性受到明确的影响.这些结果表明胼胝体对皮层细胞视觉反应的贡献是多方面的.     

大鼠旁巨细胞外侧核呼吸神经元的类型及其对某些递质类药物的反应

目的和方法用细胞外记录法和多管微电极微电泳法在36只麻醉自主呼吸的SD大鼠,系统探查旁巨细胞外侧核尾半侧(cPGCL)呼吸神经元(RNs)的类型及该区的递质受体情况。结果在14只大鼠系统探查,记录到39个RNs,包括吸气神经元24个、呼气神经元12个和跨时相神经元3个。在另22只大鼠,观察到微电泳谷氨酸钠(L-Glu)使12／14个RNs兴奋,γ-氨基丁酸(GABA)使全部受试RNs抑制(n=22);对NMDA受体拮抗剂DL-2-氨基-5-磷酸戊酸(AP     

γ-氨基丁酸能抑制对大棕蝠听皮层神经元声反应特性的影响

为了探讨γ－氨基丁酸（γ-aminobutyric acid,GABA)能抑制对大棕蝠(Eptesicus fuscus)听皮层(auditory cortex,AC)神经元声反应特性的影响,采用多管微电极电泳方法,观察了8只大棕蝠AC神经元去ABA能抑制前后声刺激诱发的反应。结果显示,微电泳GABAa受体拮抗剂荷包牡丹碱(bicuculline,Bic)去ABA能抑制可改变声刺激诱发的反应模式;极大地增加神经元冲动发放率,缩短反应的潜伏期和降低反应的最小阈值;不同程度地改变强度－发放率和强度－潜伏期函数。结果提示：1、GABA能抑制对AC神经元声信号处理起重要作用;2、GABA能抑制可改变AC神经元兴奋性支配或输入的效应,并因此定型AC神经元的声反应性质,即发放模式、阈值、强度－发放率和强度－潜伏期函数;3、GABA能抑制为AC神经元的声诱发活动提供一种调制性抑制。     

非洲爪蟾卵母细胞GABA_B和GABA_C受体介导的电流反应

实验应用双电极电压箝技术 ,在具有滤泡膜的非洲爪蟾 (Xenopuslaevis)卵母细胞上记录到γ 氨基丁酸(γ aminobutyricacid ,GABA) 激活电流。此GABA 激活电流的特点及有关GABA受体类型的研究和分析如下 :( 1)在 3 5 5 % ( 5 5 / 15 5 )的受检细胞外加GABA可引起一慢的浓度依赖性的外向电流。 ( 2 )GABAA 受体的选择性拮抗剂bicuculline ( 10 -5mol/L)对GABA ( 10 -5mol/L)引起的外向电流无阻断作用 (n =6)。 ( 3 )GABAB 受体的选择性拮抗剂2 hydroxysaclofen ( 10 -4mol/L)能将GABA ( 10 -5mol/L)引起的外向电流可逆性地转变为内向电流 ,后者又可被GABAC 受体的选择性拮抗剂I4AA ( 10 -5mol/L)所消除 (n =6)。 ( 4 )GABAB 受体的特异性激动剂baclofen可引起部分 ( 2 0 % ,12 / 60 )受检细胞产生一慢的浓度依赖性的外向电流。 3× 10 -6 、3× 10 -5及 3× 10 -4mol/L 2 hydroxysaclofen分别阻断baclofen ( 10 -5mol/L) 激活电流 ( 6 3± 3 2 ) % ,( 4 4 1± 2 2 ) %及 ( 86 0± 1 6) % (n =6)。 ( 5 )baclofen激活电流的I V曲线显示逆转电位在 - 96 8± 7 2mV左右 ,此电流可分别被TEA ( 5mmol/L)和BaCl2 ( 2mmol/L)所阻断。以上结果提示 :在非洲爪蟾的卵母细胞上存在内源性GABAB 和GABAC 受体 ,GA     

大鼠旁巨细胞外侧核呼吸神经元的型及其对某些递质类药物的反应

目的和方法：用细胞外记录法和多管微电极微电泳法在36只麻醉自主呼吸的SD大鼠,系统探查旁巨细胞外侧核尾兰侧（cPGCL）和呼吸神经元（RNs）的类型及该区的递质受体情况,结果：在14只大鼠系统探查,记录到39个RNs,包括吸气神经元24个、呼气神经元12个和跨时相神经元3个。在另22只大鼠,观察到微电泳谷氮酸钠（L－Glu)使12／14个RNs兴奋,γ－氨基丁酸（GABA）使全部受试RNs抑制(n=22);对NMDA受体拮抗剂DL－2－氨基－5－磷酸戊酸（AP5）、GABAA受体拮抗剂荷包牡丹碱（BIC）有兴奋、抑制和无作用三类效应;AP5部分阻断大部分受试神经元（6／9个）对L－Glu的兴奋反应,BIC部分或完全阻断大部分受试神经元（9／11个）,对GABA的抑制反应。结论：PGCL是呼吸调控的重要中枢部位之一,该区可能存在起神经递质作用的内源性L－Glu和GABA及兴雷性氨基酸（包括NMDA和非NMDA）受体和GABAA受体,它们可能介导PGCL对呼吸的调控。     

大鼠丘脑侧后核到初级视皮层突触传递的短时程可塑性

大鼠丘脑侧后核(lateral posterior thalamic nucleus,LP nucleus)到初级视皮层的突触连接是膝体外视觉通路的重要组成部分.运用场电位记录和电泳的方法在位研究了该视觉回路突触传递的短时程可塑性.结果表明,无论是运用双脉冲刺激还是串刺激都能观察到明显的短时程抑制特性.电泳荷包牡丹碱(bicuculline)和2-hydroxy-saclofen使该抑制作用减弱,电泳钙离子使抑制加强,电泳APV对抑制作用没有明显影响.所以突触前递质释放水平的改变,和γ-氨基丁酸(GABA)能受体（尤其是GABA_B受体）的活动都会影响该回路突触传递的短时程可塑性,而N-甲基-D-天冬氨酸(NMDA)受体则几乎没有作用.该回路很强的短时程抑制特性可能与LP核在视觉注意中的作用有关.     

甲硫—脑啡肽对大鼠DRG分离神经元ATP—激活内向电流的抑制

本研究探讨了甲硫-脑啡肽(met-Enk)对ATP-激活电流(IATP)的调制作用.实验在大鼠新鲜分离背根神经节(DRG)神经元上进行.应用全细胞膜片钳技术所记录的IATP为内向电流.在被检测的DRG神经元中,90.0%(45/50)的细胞对ATP有反应.在45个对ATP敏感的细胞中对大部分细胞(29/45)施加met-Enk(10-9～10-5mol/L)也引起一内向电流;少部分细胞(9/45)为外向电流;其余的细胞(7/45)未引起可检测的膜反应.预加met-Enk后IATP明显地被抑制,此种抑制作用为剂量依赖性的.在预加10-9、10-8、10-7、10-6、10-5mol/Lmet-Enk后,IATP的抑制分别为13.2±5.4%(n=5)、39.2±8.6%(n=8)、54.1±8.6%(n=8)、43.3±7.9%(n=7);43.1±7.9%(n=7)(mean±SKM).阿片肽拮抗剂纳洛酮能翻转此种抑制效应.IATP的量-效关系表明,预加met-Enk后曲线明显压低,在浓度为10-3mol/L时IATP下降约25%,而Kd值几乎不变.应用二次钳压技术胞内透析H-9(PKA抑制剂)能取消此种抑制作用.上述结果提示met-Enk对IATP的抑制效应为非竞争性抑制作用,可能是由于阿片受体激活后,经相应的胞内信号转导途径使ATP受体磷酸化所致.     

GABA及荷包牡丹碱对金黄地鼠上丘视觉神经...

Visual response properties of single neurons in the superior colliculus of golden hamsters could be altered by iontophoretically applied gamma-aminobutyric acid (GABA) and its antagonist, bicuculline (Bicu). GABA decreased the responses of the superficial cells to stationary flashing stimuli, while Bicu increased the responses and suppressed the inhibition exerted by the surround. The number of spikes evoked by a moving bar/spot decreased after applying GABA in 76.6% of the cells (n = 60) and increased in 90.0% (n = 60) of the cells after Bicu. Similar effects on the spontaneous activities were observed. In addition, 65.0% of the 60 cells recorded have enlarged movement receptive fields after application of Bicu. GABA and Bicu have some effects on the orientation selectivity of the collicular cells too.     

Inhibitory regulation of glutamate receptors in the frog motoneuron

The interaction of exogenously applied excitatory (glutamate and their agonists NMDA, AMPA, kainate) and inhibitory (glycine and GABA) amino acid effects was studied intracellularly in the motoneurones of the isolated frog spinal cord. During simultaneous glycine or GABA bath applications GLU-, AMPA-, KA- and NMDA-evoked responses were, respectively, decreased up to 45.8 +/- 2.9% (n = 12) and 67.8 +/- 3.9% (n = 16), 13.9 +/- 4.3% (n = 9) and 32.1 +/- 8.3% (n = 12), 36.8 +/- 8.2% (n = 7) and 48.0 +/- 11.8% (n = 6), 7.7 +/- 3.5% (n = 9) and 18.1 +/- 3.8% (n = 14) from the control. Sequential applications of EAA after glycine or GABA as well as the applications of EAA-agonist and glycine (GABA) mixture demonstrated similar results. The decrease of EAA-responses by glycine and GABA was abolished by selective GlyR antagonist strychnine (1 microM) and the selective GABAR antagonist SR95531 (gabazine, 20 MM), respectively. The data revealed differences in inhibitory effect of glycine and GABA on the excitation responses mediated by different types of glutamate receptors in the frog motoneurones: the predominant inhibitory effect of glycine and GABA on NMDA-responses and weak inhibitory effect on KA- and GLU-responses. Inhibitory effect of glycine was twice as much as that of GABA at the same concentration.     

Tonic GABAergic inhibition of taste-responsive neurons in the nucleus of the solitary tract

The effects of gamma-aminobutyric acid (GABA) and the GABAA receptor antagonist bicuculline methiodide (BICM) on the activity of taste- responsive neurons in the nucleus of the solitary tract (NST) were examined electrophysiologically in urethane-anesthetized hamsters. Single neurons in the NST were recorded extracellularly and drugs (21 nl) were microinjected into the vicinity of the cell via a multibarrel pipette. The response of each cell was recorded to lingual stimulation with 0.032 M NaCl, 0.032 M sucrose, 0.0032 M citric acid and 0.032 M quinine hydrochloride (QHCl). Forty-six neurons were tested for the effects of GABA; the activity of 29 cells (63%) was inhibited by 5 mM GABA. Whether activity was elicited in these cells by repetitive anodal current stimulation (25 microA, 0.5 s, 0.1 Hz) of the tongue (n = 13 cells) or the cells were spontaneously active (n = 13 cells), GABA produced a dose-dependent (1, 2 and 5 mM) decrement in activity. Forty- seven NST neurons were tested for the effects of BICM on their responses to chemical stimulation of the tongue; the responses of 28 cells (60%) were enhanced by 10 mM BICM. The gustatory responses of 26 of these cells were tested with three concentrations (0.2, 2 and 10 mM) of BICM, which produced a dose-dependent increase in both spontaneous activity and taste-evoked responses. Nine of these neurons were sucrose- best, seven were NaCl-best, eight were acid-best and two responded best to QHCl. The responses to all four tastants were enhanced, with no difference among neuron types. For 18 cells that were tested with two or more gustatory stimuli, BICM increased their breadth of responsiveness to their two most effective stimuli. These data show that approximately 60% of the taste-responsive neurons in the rostral NST are inhibited by GABA and/or subject to a tonic inhibitory influence, which is mediated by GABAA receptors. The modulation of these cells by GABA provides a mechanism by which the breadth of tuning of the cell can be sharpened. Modulation of gustatory activity following a number of physiological changes could be mediated by such a GABAergic circuit.      

GABA in the endocrine pancreas: cellular localization and function in normal and diabetic rats

Gamma amino butyric acid (GABA) and its related enzymes have been demonstrated in pancreatic beta cells of normal rat. Antibodies against GABA-synthesizing enzymes have been implicated in the pathogenesis of Type I diabetes. In spite of the importance of GABA in the aetiology of diabetes mellitus, detailed morphological data on the pattern of distribution of GABA in the pancreas of normal and diabetic rats are lacking. Diabetes mellitus (DM) was induced by a single dose of streptozotocin (STZ) given intraperitoneally (60 mg kg body weight(-1)). Four weeks after the induction of DM, normal (n = 6) and diabetic (n = 6) rats were anesthetized with chloral hydrate and their pancreata were removed and processed for the localization and effect of GABA on insulin secretion using immunohistochemistry and radioimmunoassay techniques. The number of GABA-like immunoreactive (GABA-LIR) cells in the pancreatic islets of STZ-diabetic rats decreased significantly (P<0.0001) when compared to non-diabetic control rats. The pattern and percentage distribution of GABA in the islet of Langerhans of normal and diabetic rat was similar to that of insulin. GABA induced a significant (P<0.0007) increase in insulin secretion from the pancreas of normal rats. In diabetic pancreas, GABA evoked a higher but not significant (P<0.1) increase in insulin secretion. These findings showed that the number of GABA-LIR cells is reduced significantly in diabetes. Moreover, GABA is a strong secretagogue of insulin from the pancreas of normal rat.     

雌、孕激素对贝美格致痫大鼠大脑皮层、海马Glu和GABA免疫反应细胞的影响

采用免疫细胞化学双PAP法,观察雌二醇（E2）、孕酮（P）对贝美格（Bemegride,Be）腹腔致痫大鼠顶叶大脑皮层、海马CA1、CA3区Glu和GABA免疫反应细胞的影响。图像分析结果显示：Be致痫组皮层、海马Glu免疫反应平均阳性细胞数及光密度较正常组明显增加（P＜0.01）;CABA细胞数及光密度减少（P＜0.01）。给予E2后,Be致痫大鼠大脑皮层、海马Glu阳性细胞数目增多,光密度增高（P＜0.01）,GABA阳性细胞数目减少、光密度降低（P＜0.05,P＜0.01）而给予P后,致痫组GABA阳性细胞数目增多、光密度增高（P＜0.01）,Glu阳性细胞数目减少、光密度减低（P＜0.01）。提示雌、孕激素的致痫、抗痫作用与其调节脑内GABA和Glu系统的兴奋性有关。     

Electrophysiological actions of VIP in rat somatosensory cortex.

Electrophysiological and biochemical studies suggest that VIP may exert a facilitating action in the neocortical local circuitry. In the present study, we examined the actions of VIP and VIP + norepinephrine (NE) on somatosensory cortical neuron responses to direct application of the putative transmitters acetylcholine (ACh) and gamma-aminobutyric acid (GABA). Spontaneous and transmitter-induced discharges of cortical neurons from halothane-anesthetized rats were monitored before, during and after VIP, NE and VIP + NE iontophoresis. In 57 VIP-sensitive cells tested, VIP application (5-70 nA) increased (n = 18), decreased (n = 36) or had biphasic actions (n = 3) on background firing rate. In a group of 20 neurons tested for NE + VIP, the combined effect of both peptide and bioamine was predominantly (70%) inhibitory. On the other hand, inhibitory and excitatory responses of cortical neurons to GABA (11 of 15 cases) and ACh (10 of 18 cases), respectively, were enhanced during VIP iontophoresis. Concomitant application of VIP and NE produced additive (n = 2) or more than additive (n = 3) enhancing effects on GABA inhibition. NE administration reversed or enhanced further VIP modulatory actions on ACh-induced excitation. These findings provide electrophysiological evidence that NE and VIP afferents may exert convergent influences on cortical neuronal responses to afferent synaptic inputs such that modulatory actions are anatomically focused within the cortex.     

Effect of ammonia on GABA uptake and release in cultured astrocytes

While the pathogenesis of hepatic encephalopathy (HE) is unclear, there is evidence of enhanced GABAergic neurotransmission in this condition. Ammonia is believed to play a major pathogenetic role in HE. To determine whether ammonia might contribute to abnormalities in GABAergic neurotransmission, its effects on GABA uptake and release were studied in cultured astrocytes, cells that appear to be targets of ammonia neurotoxicity. Acutely, ammonium chloride (5 mM) inhibited GABA uptake by 30%, and by 50-60% after 4-day treatment. GABA uptake inhibition was associated with a predominant decrease in Vmax; the Km was also decreased. Ammonia also enhanced GABA release after 4-day treatment, although such release was initially inhibited. These effects of ammonia (inhibition of GABA uptake and enhanced GABA release) may elevate extracellular levels of GABA and contribute to a dysfunction of GABAergic neurotransmission in HE and other hyperammonemic states.     

Acute and long-lasting effects of peripheral injection of caerulein and CCK-8 on the central GABAergic system in mice

Acute and long-lasting effects of peripheral injection of caerulein (CLN) and cholecystokinin octapeptide (CCK-8) on the gamma-aminobutylic acid (GABA) content and the GABA accumulation by aminooxyacetic acid (AOAA) in the discrete brain regions of mice were examined. The content and accumulation of GABA in the striatum, hypothalamus, and frontal cortex was measured with high performance liquid chromatography with electrochemical detection (HPLC-ECD). The GABA content slightly decreased in the striatum 60 min after CLN and CCK-8 were administered, whereas it slightly increased in the hypothalamus and frontal cortex. Moreover, with CLN and CCK-8, the GABA accumulation after AOAA treatment decreased in the striatum and hypothalamus 30 min after injection. Meanwhile, when administering CLN, the GABA content as well as the GABA accumulation after AOAA treatment increased in the striatum and frontal cortex 1 day after injection, and continued to increase the second and third day in the striatum. These results showed that peripheral injection of CLN and CCK-8 had effects on the central GABAergic system with local specific actions, and also the long-lasting and time-dependent biphasic effects of CLN.     

GABA maintains the proliferation of progenitors in the developing chick ciliary marginal zone and non-pigmented ciliary epithelium

GABA is more than the main inhibitory neurotransmitter found in the adult CNS. Several studies have shown that GABA regulates the proliferation of progenitor and stem cells. This work examined the effects of the GABA(A) receptor system on the proliferation of retinal progenitors and non-pigmented ciliary epithelial (NPE) cells. qRT-PCR and whole-cell patch-clamp electrophysiology were used to characterize the GABA(A) receptor system. To quantify the effects on proliferation by GABA(A) receptor agonists and antagonists, incorporation of thymidine analogues was used. The results showed that the NPE cells express functional extrasynaptic GABA(A) receptors with tonic properties and that low concentration of GABA is required for a baseline level of proliferation. Antagonists of the GABA(A) receptors decreased the proliferation of dissociated E12 NPE cells. Bicuculline also had effects on progenitor cell proliferation in intact E8 and E12 developing retina. The NPE cells had low levels of the Cl-transporter KCC2 compared to the mature retina, suggesting a depolarising role for the GABA(A) receptors. Treatment with KCl, which is known to depolarise membranes, prevented some of the decreased proliferation caused by inhibition of the GABA(A) receptors. This supported the depolarising role for the GABA(A) receptors. Inhibition of L-type voltage-gated Ca(2+) channels (VGCCs) reduced the proliferation in the same way as inhibition of the GABA(A) receptors. Inhibition of the channels increased the expression of the cyclin-dependent kinase inhibitor p27(KIP1), along with the reduced proliferation. These results are consistent with that when the membrane potential indirectly regulates cell proliferation with hyperpolarisation of the membrane potential resulting in decreased cell division. The increased expression of p27(KIP1) after inhibition of either the GABA(A) receptors or the L-type VGCCs suggests a link between the GABA(A) receptors, membrane potential, and intracellular Ca(2+) in regulating the cell cycle.