Swann J W, Brady R J, Martin D L
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
Neuroscience. 1989;28(3):551-61. doi: 10.1016/0306-4522(89)90004-3.
Developmental alterations in GABAergic synaptic transmission were examined physiologically and biochemically in hippocampus of rats from 3 days of age to adulthood. Neither antidromic nor orthodromic stimulation could elicit identifiable inhibitory postsynaptic potentials in CA1 neurons in slices from rats 5 or 6 days of age. In contrast, at this age these stimuli result in large inhibitory postsynaptic potentials in CA3 pyramidal cells. In the latter cells orthodromic stimulation produced a brief monosynaptic excitatory postsynaptic potential which was followed by a large prolonged biphasic hyperpolarization. These signals were strikingly similar to those recorded in 1-month-old rats. In addition, large recurrent inhibitory postsynaptic potentials were produced by antidromic stimulation. By postnatal day 9 similar inhibitory postsynaptic potentials could be elicited in a majority of neurons of the CA1 subfield. As in mature pyramidal cells, application of GABA antagonists, such as bicuculline, selectively eliminated the antidromic inhibitory postsynaptic potential and the first component of the biphasic inhibitory postsynaptic potential generated by stimulation of stratum radiatum. In the CA3 subfield, this blockade of GABA receptors resulted in prolonged afterdischarges in slices from immature but not month-old rats. Measurements of the equilibrium potential and the conductance of antidromic inhibitory postsynaptic potentials in CA3 neurons were very similar when made during the first postnatal week and at 1 month of age. While on days 10-11 the equilibrium potential was very similar to measurements made at these other ages, the conductance was 3-4 times greater. The activity of glutamate decarboxylase, the synthetic enzyme for GABA, was very low at 3 days in hippocampus, and increased until 30 days of age at which time adult values were obtained. By comparison, hippocampal GABA levels were high early in postnatal life. Glutamate decarboxylase activities in microdissected CA3 and CA1 subfields were similar in immature hippocampus. These results demonstrate dramatic differences in the ontogenesis of functional GABAergic inhibitory synaptic transmission in the CA1 and CA3 subfields of rat hippocampus. The late development of GABA-mediated synaptic inhibition in the CA1 subfield could play a role in the susceptibility of immature hippocampus to seizures. However, the large GABA-mediated inhibitory postsynaptic potentials present in the CA3 subfield at the same age have a critical role in dampening neuronal excitability.(ABSTRACT TRUNCATED AT 400 WORDS)
从3日龄至成年期的大鼠海马中,对γ-氨基丁酸能(GABAergic)突触传递的发育变化进行了生理学和生物化学研究。在5或6日龄大鼠脑片的CA1神经元中,无论是逆向刺激还是顺向刺激,均无法诱发可识别的抑制性突触后电位。相比之下,在这个年龄段,这些刺激在CA3锥体细胞中可产生较大的抑制性突触后电位。在后者细胞中,顺向刺激产生一个短暂的单突触兴奋性突触后电位,随后是一个大的、持续时间长的双相超极化。这些信号与在1月龄大鼠中记录到的信号惊人地相似。此外,逆向刺激可产生较大的反复抑制性突触后电位。到出生后第9天,在CA1亚区的大多数神经元中可诱发类似的抑制性突触后电位。与成熟锥体细胞一样,应用GABA拮抗剂,如荷包牡丹碱,可选择性消除逆向刺激诱发的抑制性突触后电位以及刺激辐射层产生的双相抑制性突触后电位的第一成分。在CA3亚区,这种对GABA受体的阻断在未成熟大鼠而非1月龄大鼠的脑片中导致放电后延长。在出生后第一周和1月龄时测量CA3神经元逆向抑制性突触后电位的平衡电位和电导非常相似。虽然在第10 - 11天时平衡电位与在其他这些年龄段测量的值非常相似,但电导大3 - 4倍。GABA合成酶谷氨酸脱羧酶的活性在海马中3日龄时非常低,并一直增加到30日龄时达到成年水平。相比之下,海马中的GABA水平在出生后早期较高。在未成熟海马中,显微解剖的CA3和CA1亚区的谷氨酸脱羧酶活性相似。这些结果表明大鼠海马CA1和CA3亚区功能性GABA能抑制性突触传递的个体发生存在显著差异。CA1亚区中GABA介导的突触抑制的延迟发育可能在未成熟海马对癫痫发作的易感性中起作用。然而,在同一年龄的CA3亚区中存在的大的GABA介导的抑制性突触后电位在抑制神经元兴奋性方面起关键作用。(摘要截选至400字)