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Effects of GABA receptor blockade on the ventilatory response to hypoxia in hypothermic newborn piglets

PEDIATRIC RESEARCH 2000年第5期47卷 663-668页

作者： Xiao, QM Suguihara, C Hehre, D Devia, C Huang, J Bancalari, E Univ Miami Sch Med Dept Pediat Div Neonatol Miami FL 33101 USA

Hypothermic newborn piglets have a depressed ventilatory response to hypoxia, and this may be due to an increase in CNS gamma-aminobutyric acid (GABA) levels. To evaluate the effects of GABA(A) receptor blockade on the ventilatory response to hypoxia in hypothermic piglets, 31 anesthetized paralyzed mechanically ventilated newborn piglets (2-7 d) were studied at a brain temperature of 38.5 +/- 0.5 degrees C [normothermia (NT), n = 15] or 34 +/- 0.5 degrees C [hypothermia (HT), n = 16]. The central respiratory output was evaluated by measuring burst frequency and moving time average area of phrenic nerve activity. Measurements of minute phrenic output (MPO), arterial blood pressure, heart rate, oxygen consumption, and arterial blood gases were obtained at room air and during 20 min of isocapnic hypoxia [fraction of expired oxygen (Fio(2)) = 0.10], After 10 min of hypoxia, a bolus injection of 20 mu L of bicuculline methiodide (BM;10 mu g) or Ringer's solution was administered into the cisterna magna over a I-min period, and the piglets remained in hypoxia for an additional 10 min. There was an initial increase of 50 +/- 6% in MPO during the first minute of hypoxia followed by a decrease to values 24 +/- 8% above baseline at 10 min in the NT group. In contrast, in the HT group, the initial increase in MPO with hypoxia was eliminated, and, at 10 min, there was a decrease to a mean value 35 +/- 4% below baseline level (NT versus HT, p < 0.03). After administration of BM, a significant increase in MPO with hypoxia was observed in both groups compared with their placebo groups (p < 0.002 in NT-BM group, p < 0.0001 in HT-BM group). However, the magnitude of the increase in MPO during hypoxia was significantly greater in the HT group after administration of BM (NT versus HT, p < 0.0001). Changes in oxygen consumption, arterial blood pressure, heart rate, pH, partial pressure of oxygen (Pao(2)), and base excess with hypoxia were not different between NT and HT groups before

关键词：酸碱平衡/药物作用动物新生荷包牡丹碱/投药和剂量荷包牡丹碱/类似物和衍生物血气分析血压/药物作用体重 GABA拮抗剂/药理学 GABA-A受体拮抗剂心率/药物作用低温人工注射脑室内氧耗量/药物作用膈神经/药物作用膈神经/生理学呼吸/药物作用呼吸人工猪动物

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Long-term suppression of synaptic transmission by tetanization of a single pyramidal cell in the mouse hippocampus in vitro

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第3期515卷 757-767页

作者： Yanovsky, Y Haas, HL Univ Dusseldorf Dept Physiol 2 Inst Neurophysiol D-40001 Dusseldorf Germany

1. The consequences of stimulating a single pyramidal cell in the CA1 area of the hippocampus for synaptic transmission in the stratum radiatum were investigated. 2. Tetanic activation of single pyramids caused by depolarizing current injection, but not an equal number of distributed action potentials, reduced excitatory transmission by 20%, with a delayed onset, for more than 1 h. 3. EPSPs in the tetanized pyramidal cells were increased for equally long periods but this was not the cause of the field EPSP reduction. Spontaneous somatic IPSPs were not affected;evoked IPXPs were decreased in the tetanized cell. 4. Paired pulse facilitation of the field EPSPs was unchanged. 5. The field EPSP reduction nias markedly diminished by a knife cut along the base of pyramidal cells in CA1. 6. The addition of antagonists of GABA, NMDA and metabotropic glutamate receptors blocked or diminished the field EPSP slope reduction evoked by intracellular stimulation. 7. Simultaneous recordings revealed long-lasting excitations of interneurons located in the outer oriens layer as a result of single pyramid tetanization. 8. Intense firing of small numbers of pyramidal cells can thus persistently inhibit mass transmission through the hippocampus. This effect involves activation of interneurons by glutamate receptors.

关键词： 2-氨基-5-膦酰基戊酸盐/药理学苯甲酸盐类/药理学荷包牡丹碱/类似物和衍生物荷包牡丹碱/药理学电刺激兴奋性氨基酸拮抗剂/药理学兴奋性突触后电位/药物作用兴奋性突触后电位/生理学 GABA拮抗剂/药理学甘氨酸/类似物和衍生物甘氨酸/药理学海马/生理学小鼠近交系 N-甲基天冬氨酸/拮抗剂和抑制剂次膦酸类/药理学丙醇胺类/药理学锥体细胞/药物作用锥体细胞/生理学受体亲代谢性谷氨酸盐/拮抗剂和抑制剂突触传递/药物作用突触传递/生理学动物男(雄)性小鼠

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Visual input induces long-term potentiation of developing retinotectal synapses

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NATURE NEUROSCIENCE 2000年第7期3卷 708-715页

作者： Zhang, LI Tao, HW Poo, M Univ Calif San Diego Dept Biol La Jolla CA 92093 USA

Early visual experience is essential in the refinement of developing neural connections. In vivo whole-cell recording from the tectum of Xenopus tadpoles showed that repetitive dimming-light stimulation applied to the contralateral eye resulted in persistent enhancement of glutamatergic inputs, but not GABAergic or glycinergic inputs, on tectal neurons. This enhancement can be attributed to potentiation of retinotectal synapses. It required spiking of postsynaptic tectal cells as well as activation of NMDA receptors, and effectively occluded long-term potentiation (LTP) of retinotectal synapses induced by direct electrical stimulation of retinal ganglion cells. Thus, LTP-like synaptic modification can be induced by natural visual inputs and may be part of the underlying mechanism for the activity-dependent refinement of developing connections.

关键词： 2-氨基-5-膦酰基戊酸盐/药理学 6-氰-7-硝基喹喔啉-2 3-二酮/药理学荷包牡丹碱/类似物和衍生物荷包牡丹碱/药理学二羧酸类/药理学光长时程增强/药物作用长时程增强/生理学神经元/药物作用神经元/生理学神经递质摄取抑制药/药理学光刺激吡咯烷类/药理学视网膜/生理学突触/药物作用突触/生理学视通路/生理学视知觉/生理学爪蟾属动物

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Serotonergic modulation of neurotransmission in the rat basolateral amygdala

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JOURNAL OF NEUROPHYSIOLOGY 1999年第1期82卷 69-85页

作者： Rainnie, DG Harvard Univ Sch Med Brockton MA 02301 USA Brockton VAMC Dept Psychiat Neurosci Lab 151C Brockton MA 02301 USA

Serotonergic modulation of neurotransmission in the rat basolateral amygdala. J. Neurophysiol. 82. 69-85, 1999. Whole cell patch-clamp recordings were obtained from projection neurons and interneurons of the rat basolateral amygdala (BLA) to understand local network interactions in morphologically identified neurons and their modulation by serotonin. Projection neurons and interneurons were characterized morphologically and electrophysiologically according to their intrinsic membrane properties and synaptic characteristics. Syn aptic activity in projection neurons was dominated by spontaneous inhibitory postsynaptic currents (IPSCs) that were multiphasic, reached 181 +/- 38 pA in amplitude, lasted 296 +/- 27 mS, and were blocked by the GABA(A) receptor antagonist, bicuculline methiodide (30 mu M). In interneurons, spontaneous synaptic activity was characterized by a burst-firing discharge patterns (200 +/- 40 Hz) that correlated with the occurrence of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive high-amplitude (260 +/- 42 pA), long-duration (139 +/- 19 mS) inward excitatory postsynaptic currents (EPSCs). The interevent interval of 831 +/- 344 mS for compound inhibitory postsynaptic potentials (IPSPs), and 916 +/- 270 mS for EPSC bursts, suggested that spontaneous IPSP/Cs in projection neurons are driven by burst of action potentials in interneurons. Hence, BLA interneurons may regulate the excitability of projection neurons and thus determine the degree of synchrony within ensembles of BLA neurons. In interneurons 5-hydroxytryptamine oxalate (5-HT) evoked a direct, dose-dependent. membrane depolarization mediated by a 45 +/- 6.9 pA inward current, which had a reversal potential of -90 mV. The effect of 5-HT was mimicked by the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT), but not by the 5-HT1A receptor agonist, (+/-) 8-hydroxydipropylaminotetralin hydrobromide (8-QH-DPAT), or the 5-HT1B agonist, CGS 12066A. In projection neurons, 5-

关键词： 8-羟-2-(二-n-丙胺)四氢萘/药理学杏仁核/药物作用杏仁核/生理学荷包牡丹碱/类似物和衍生物荷包牡丹碱/药理学诱发电位/药物作用诱发电位/生理学兴奋性突触后电位/药物作用兴奋性突触后电位/生理学 GABA-A受体拮抗剂中间神经元/细胞学中间神经元/药物作用中间神经元/生理学神经元/细胞学神经元/药物作用神经元/生理学膜片钳术喹恶啉类/药理学大鼠 Long-Evans 受体血清素 5-HT1B 受体血清素/生理学受体血清素 5-HT1 血清素/类似物和衍生物血清素/药理学血清素/生理学血清素受体激动剂/药理学突触传递/药物作用突触传递/生理学河豚毒素/药理学动物男(雄)性大鼠

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Robust suppression of afferent-induced excitation in the rat spinal dorsal horn after conditioning low-frequency stimulation

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JOURNAL OF NEUROPHYSIOLOGY 1999年第4期82卷 1957-1964页

作者： Ikeda, H Asai, T Randic, M Murase, K Fukui Univ Dept Human & Artificial Intelligence Syst Fukui 910 Japan Iowa State Univ Dept Biomed Sci Ames IA 50011 USA

The neuronal plasticity in the spinal dorsal horn induced after conditioning low-frequency stimulation of afferent A fibers, and its relationship with spinal inhibitory networks, was investigated with an optical-imaging method that detects neuronal excitation. High-intensity single-pulse stimulation of the dorsal root activating both A and C fibers evoked an optical response in the dorsal horn in transverse slices of 12- to 25-day-old rat spinal cords stained with a voltage-sensitive dye, RH-482. The optical response, reflecting the net excitation of neuronal elements along the thickness of each slice, was suppressed after a conditioning low-frequency stimulation (0.2-1 Hz for 10 min) to A fibers in the dorsal root. The degree of suppression was largest in the lamina II of the dorsal horn (48% reduction), where the majority of C fibers terminate, and much less in the deeper dorsal horn (5% reduction in laminae III-IV). The onset of suppression was somewhat slow;after the low-frequency stimulation, the magnitude of excitation gradually decreased, reached the maximum effect 30 min after the conditioning, and remained at the suppressed level for >1 h. Suppression was not observed when the low-frequency stimulation was given during a 20-min perfusion with a solution containing an NMDA-receptor antagonist, DL-2-amino-5-phosphonovaleric acid (30 mu M). A brief application of an opioid-receptor antagonist, naloxone (0.5 mu M), inhibited the induction, but not the maintenance, of low-frequency stimulus-induced suppression. However, treatments with the GABA, receptor antagonist bicuculline (1 mu M) and the glycine receptor antagonist strychnine (0.3 mu M) did not affect suppression induction and maintenance. In conclusion, conditioning low-frequency stimulation to A fibers interferes with the afferent-induced excitation in the dorsal horn. The low-frequency stimulation-induced suppression is maintained by a reduction of glutamatergic excitatory transmissions in the dorsal ho

关键词： 2-氨基-5-膦酰基戊酸盐/药理学传入通路/生理学荷包牡丹碱/类似物和衍生物荷包牡丹碱/药理学电刺激诱发电位/药物作用诱发电位/生理学兴奋性氨基酸拮抗剂/药理学纳洛酮/药理学神经纤维/药物作用神经纤维/生理学神经元可塑性/生理学后角细胞/药物作用后角细胞/生理学大鼠 Sprague-Dawley 反应时间士的宁/药理学动物大鼠

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Mechanisms underlying LTP of inhibitory synaptic transmission in the deep cerebellar nuclei

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JOURNAL OF NEUROPHYSIOLOGY 2000年第3期84卷 1414-1421页

作者： Ouardouz, M Sastry, BR Univ British Columbia Fac Med Dept Pharmacol & Therapeut Neurosci Res Lab Vancouver BC V6T 1Z3 Canada

Whole-cell recordings were used to investigate long-term potentiation of inhibitory synaptic currents (IPSCs) in neurons of deep cerebellar nuclei (DCN) in slices. IPSCs were evoked by electrical stimulation of the white matter surrounding the DCN in the presence of non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (20 mu M). High-frequency stimulation induced a long-term potentation (LTP) of the IPSC amplitude without changing its reversal potential, rise time, and decay-time constant. This LTP did not require the activation of postsynaptic gamma-aminobutyric acid-A (GABA(A)) receptors but depended on the activation of NMDA receptors. LTP of IPSCs in DCN neurons could also be induced by voltage-depolarizing pulses in postsynaptic neurons and appeared to depend on an increase in intracellular calcium as the LTP was blocked when the cells were loaded with a calcium chelator, 1,2-bis-(2-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA, 10 mM). LTP of IPSCs was accompanied by an increase in the frequency of spontaneous IPSCs and miniature IPSCs (recorded in the presence of tetrodotoxin 1 mM), but there was no significant change in their amplitude. In addition, during the LTP, the amplitude of response to exogenously applied GABA(A) receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride was increased. Intracellular application of tetanus toxin, a powerful blocker of exocytosis, in DCN neuron prevented the induction of LTP of IPSCs. Our results suggest that the induction of LTP of IPSCs in the DCN neurons likely involves a postsynaptic locus. Plasticity of inhibitory synaptic transmission in DCN neurons may play a crucial role in cerebellar control of motor coordination and learning.

关键词： 2-氨基-5-膦酰基戊酸盐/药理学动作电位/药物作用荷包牡丹碱/类似物和衍生物荷包牡丹碱/药理学钙/代谢小脑核/细胞学小脑核/代谢螯合剂/药理学电刺激兴奋性氨基酸拮抗剂/药理学 GABA激动剂/药理学 GABA拮抗剂/药理学 GABA-A受体激动剂 GABA-A受体拮抗剂细胞内液/代谢长时程增强/药物作用长时程增强/生理学神经抑制/生理学膜片钳术喹恶啉类/药理学受体 GABA-A/代谢受体 N-甲基-D-天冬氨酸/拮抗剂和抑制剂受体 N-甲基-D-天冬氨酸/代谢突触传递/生理学破伤风毒素/药理学动物大鼠

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Effects of GABA receptor antagonist on trigeminal caudalis nociceptive neurons in normal and neonatally capsaicin-treated rats

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JOURNAL OF NEUROPHYSIOLOGY 1999年第5期82卷 2154-2162页

作者： Chiang, CY Kwan, CL Ku, JW Sessle, BJ Univ Toronto Fac Dent Toronto ON M5G 1G6 Canada

We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-D-aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABA(A) receptor antagonist bicuculline (BIC) or the GABA(B) receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Ve nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABA(A) receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABA(B) receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABA(A) receptor blockade by SAC (i.t.) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABA(A) receptor-mediated inhibitio

关键词：动物新生巴氯芬/类似物和衍生物巴氯芬/药理学荷包牡丹碱/类似物和衍生物荷包牡丹碱/药理学脑图辣椒辣素/投药和剂量辣椒辣素/药理学功能偏侧化 GABA拮抗剂/药理学 GABA-A受体拮抗剂延髓/药物作用延髓/生理学微量注射神经元可塑性/药物作用神经元可塑性/生理学神经元/药物作用神经元/生理学疼痛感受器/药物作用疼痛感受器/生理学疼痛/病理生理学物理刺激大鼠 Sprague-Dawley 触觉三叉神经/药物作用三叉神经/生理学三叉神经/病理生理学动物男(雄)性大鼠

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