GABA--EXCITATORY TRANSMITTER IN DEVELOPING HYPOTHALAMUS

描述（研究者摘要）：这是一项测试 一般假设GABA在发育中起兴奋作用， 下丘脑的大鼠，相反，其公认的作用， 抑制性神经递质。融合方法，利用 Fura-2数字钙成像、免疫细胞化学和全细胞贴片 钳记录将使用培养的神经元测试五个特定的假设 或下丘脑切片。首先，GABA被假设为去乙酰化， 膜，增加神经元活性，并增加细胞内钙 在发育早期，但不是晚期。第二，建议 谷氨酸介导的突触活动加速了 在成人中观察到的GABA抑制作用。第三，PI将测试 GABA是否在下丘脑早期合成和释放 发展第四，GABA被认为促进细胞存活， 增加突触发生，影响细胞运动，并增加神经突 早期发展的结果。最后，做抑制动作， GABA在成人神经元损伤后恢复到抑制作用？ 这种逆转可能对神经元的反应方式产生重要影响 钙介导的毒性以及它们对GABA的反应。 由于许多下丘脑回路是抑制性的，并由GABA介导， 在成年期，GABA的早期兴奋作用可能对正常 发展

DESCRIPTION (Investigator's Abstract): This is a proposal to test the general hypothesis that GABA plays an excitatory role in the developing hypothalamus of the rat, in contrast to its accepted role as an inhibitory neurotransmitter in the adult. Converging approaches utilizing fura-2 digital calcium imaging, immunocytochemistry and whole cell patch clamp recording will test five specific hypotheses using cultured neurons or hypothalamic slices. First, GABA is hypothesized to depolarize the membrane, increase neuronal activity, and increase intracellular calcium early, but not late, in development. Secondly, it is proposed that glutamate-mediated synaptic activity accelerates the maturation of the inhibitory actions of GABA seen in adults. Thirdly, the PI will test whether GABA is synthesized and released during early hypothalamic development. Fourthly, GABA is proposed to promote cell survival, increase synaptogenesis, influence cell motility, and increase neurite outgrowth in early development. Finally, do the inhibitory actions of GABA in the adult revert to inhibitory actions following neuronal injury? This reversion may have important consequences for how neurons respond to calcium-mediated toxicity and how they respond to GABA in general. Since many hypothalamic circuits are inhibitory and mediated by GABA in the adult, GABA's early excitatory actions may be crucial for normal development.