Harsanyi K, Friedlander M J
Department of Neurobiology, University of Alabama at Birmingham 35294, USA.
J Neurophysiol. 1997 Mar;77(3):1284-93. doi: 10.1152/jn.1997.77.3.1284.
In our previous study, pairing-induced transient synaptic potentiation in supragranular layers of the visual cortex was described in mature guinea pigs. In the present study, the development of this type of synaptic plasticity and the underlying cellular mechanisms that mediate it were evaluated in animals from postnatal day (PND) 5 to 180. Potentiation is more reliably evoked in younger animals (likelihood: 75%, PND 5-30; 51%, PND > or = 34), and the magnitude of the effect is greater (+40 +/- 3%, mean +/- SE, PND 5-30; +26 +/- 3%, PND > or = 34). Similar to data obtained from the mature animals, visual cortical transient synaptic potentiation in the immature cortex occurs at excitatory synaptic sites directly activated by the stimulation, and activation by local recurrent cortical circuits is not necessary for the induction of this potentiation. This is demonstrated by 1) experiments in which action potential output from the paired neuron was blocked by Lidocaine, N-ethyl bromide quaternary salt applied into the neuron (5 of 5), and 2) experiments in which the contribution to the compound postsynaptic potential by inhibitory synapses was eliminated by selective, intracellular blockade by gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials only onto the recorded neuron (7 of 11). Thus these perturbations do not reduce the likelihood or magnitude of this synaptic potentiation. In contrast to the N-methyl-D-aspartate (NMDA) receptor dependence for induction of this synaptic potentiation in the cortex of mature animals, in the young animals' cortices (PND 11-27) potentiation is readily induced during blockade of NMDA receptors (72%, 13 of 18, did not different from control: 75%, 40 of 53). Thus the NMDA receptor becomes functionally linked to a synaptic potentiation cascade during development, replacing another 2-amino-5-phosphonovaleric acid (APV)-insensitive potentiation process in the neonatal cortex. Postsynaptic intracellular calcium has a critical role in the induction of this form of synaptic potentiation in all ages studied. Synaptic potentiation was prevented (8 of 11 cases) or was replaced by synaptic depression (3 of 11 cells) in experiments in which postsynaptic calcium levels were reduced by intracellular application of 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in the cortex of young (PND 7-14) animals, or in which the extracellular calcium concentrations was lowered. Inhibition of postsynaptic calcium-induced calcium release blocked synaptic potentiation (4 of 4 cells). Prolonged superfusion (3 h) of the nitric oxide synthase inhibitor L-nitro-arginine (LNA) did not significantly affect the likelihood (in LNA, 81%; 13 of 16 cells), or the magnitude (+38 +/- 7% increase in LNA vs. +40 +/- 3% in control cases) of potentiation, in contrast to its effects in the mature cortex.
在我们之前的研究中，描述了成熟豚鼠视皮层颗粒上层中配对诱导的短暂性突触增强。在本研究中，对出生后第5天（PND）至180天的动物，评估了这种突触可塑性的发育及其潜在的细胞介导机制。在较年幼的动物中更可靠地诱发增强（可能性：75%，PND 5 - 30；51%，PND≥34），且效应幅度更大（+40±3%，平均值±标准误，PND 5 - 30；+26±3%，PND≥34）。与从成熟动物获得的数据相似，未成熟皮层中的视皮层短暂性突触增强发生在由刺激直接激活的兴奋性突触部位，并且局部皮层回路的激活对于这种增强的诱导不是必需的。这通过以下实验得以证明：1）将利多卡因、N - 乙基溴化季铵盐注入神经元来阻断配对神经元的动作电位输出的实验（5例中有5例），以及2）通过仅对记录神经元进行γ - 氨基丁酸介导的抑制性突触后电位的选择性细胞内阻断来消除抑制性突触对复合突触后电位贡献的实验（11例中有7例）。因此，这些干扰不会降低这种突触增强的可能性或幅度。与成熟动物皮层中这种突触增强的诱导依赖N - 甲基 - D - 天冬氨酸（NMDA）受体不同，在幼小动物的皮层（PND 11 - 27）中，在NMDA受体阻断期间很容易诱导增强（72%，18例中有13例，与对照无差异：75%，53例中有40例）。因此，在发育过程中，NMDA受体在功能上与突触增强级联相关联，取代了新生皮层中另一种对2 - 氨基 - 5 - 磷酸缬氨酸（APV）不敏感的增强过程。在所有研究的年龄段中，突触后细胞内钙在这种形式的突触增强的诱导中起关键作用。在幼龄（PND 7 - 14）动物皮层中，通过细胞内应用1,2 - 双（2 - 氨基苯氧基）乙烷 - N,N,N',N' - 四乙酸（BAPTA）降低突触后钙水平的实验中，或者在降低细胞外钙浓度的实验中，突触增强被阻止（11例中有8例）或被突触抑制所取代（11个细胞中有3个）。抑制突触后钙诱导的钙释放可阻断突触增强（4个细胞中有4个）。与它在成熟皮层中的作用相反，一氧化氮合酶抑制剂L - 硝基精氨酸（LNA）的长时间灌注（3小时）对增强的可能性（在LNA中为81%；16个细胞中有13个）或幅度（LNA中增加+38±7%，对照中为+40±3%）没有显著影响。
