皮层GABA能神经元的发育成熟及神经网络功能稳态
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- 英文论文题名：Development and maturation of cortical GABAergic interneurons and homeostatic neuronal networks
- 论文作者：乔婧 ; 陈焕新
- 英文论文作者：Jing Qiao ; Huanxin Chen ; Translational Research Center ; Faculty of Psychology ; Southwest University
- 年：2015
- 作者机构：西南大学心理学部转化研究中心;
- 论文关键词：GABA能神经元 ; 皮层 ; 糖皮质激素受体 ; 应激 ; 稳态
- 英文论文关键词：GABAergic neurons ; cortex ; glucocorticoid receptors ; stress ; homeostasis
- 会议召开时间：2015-10-16
- 会议录名称：第十八届全国心理学学术会议摘要集——心理学与社会发展
- 英文会议录名称：Proceedings of the 18th National Academic Congress of Psychology
- 语种：中文
- 分类号：B845.1
- 学会代码：ZGXG
- 会议名称：第十八届全国心理学学术会议
- 会议地点：中国天津
- 主办单位：中国心理学会
- 学会名称：中国心理学会
- 页数：2
- 文件大小：753k
- 原文格式：D
- 会议级别：全国
摘要
谷氨酸能兴奋性神经元和GABA能抑制性神经元是大脑皮层的两类主要神经元,这些神经元之间通过兴奋性和抑制性突触相互作用,形成网络。大脑的正常功能有赖于网络的兴奋与抑制活动的相对平衡。研究发现,抑郁症、精神分裂症等精神类疾病与神经网络活动的失衡相关。皮层GABA能神经元根据其形态、电生理特性、含有的特殊分子分为多种亚型,每种亚型存在不同的功能。皮层GABA能神经元主要由表达小白蛋白(Parvalbumin,PV)和生长激素抑制素(Somatostatin,SOM)的两类亚型构成。应用电生理和免疫组化方法,我们分别研究了PV和SOM神经元内在属性和突触功能的发育成熟及糖皮质激素受体的在两类神经元上的表达。结果表明,出生后第一个月,神经元发放动作电位的频率和兴奋性突触活动逐渐增强。动作电位频率的增强与Kv3钾离子通道表达增强相关,而突触活动增强可能与突触数量的增加有关。这些发育变化对神经元本身的成熟及对神经网络的功能稳态起重要作用。免疫组化结果表明,两类皮层GABA能神经元上表达丰富的糖皮质激素受体。慢性应激引起糖皮质激素水平持续增高,可能损坏GABA能神经元的功能,破坏神经网络的稳态,导致精神神经疾病的产生。我们进一步的研究将揭示这些可能的变化和机制,为新药研发提供新的分子靶点。
Glutamatergic and GABAergic neurons are two major types of neurons in the cortex. They interact through excitatory and inhibitory synapses, and form neuronal networks. Normal functions of the brain rely on the balanced excitation and inhibition of neuronal network. Studies found that unbalanced networks may lead to a variety of mental disorders, such as depression and schizophrenia. Cortical GABAergic interneurons are categorized into many different subtypes according to their morphology, electrophysiological property and specific molecule. Majority of cortical GABAergic neurons are parvalbumin(PV) expressing and somatostatin(SOM) expressing neurons. We have studied the developmental changes of intrinsic and synaptic properties of the two subtype neurons, and the expression of glucocorticoid receptors on them using electrophysiology and immunohistochemistry. We found the marked enhancement in the firing rate of action potentials and excitatory synaptic activities in the first month after the birth, which may be due to the developmental increase in Kv3 potassium channels and formation of synapses respectively. These developmental changes may play an important role in maturation of neurons themselves and also homeostasis of networks. We also found that glucocorticoid receptors are richly expressed in both subtypes. Chronic stress induces a prolonged increase in the concentration of glucocorticoids which may affect the function of interneurons and damage homeostasis of neuronal network, leading to mental and neurological disorders. Our further study will explore these possible stress-related effects and the mechanisms, which will provide new targets for the development of novel therapies.
Glutamatergic and GABAergic neurons are two major types of neurons in the cortex. They interact through excitatory and inhibitory synapses, and form neuronal networks. Normal functions of the brain rely on the balanced excitation and inhibition of neuronal network. Studies found that unbalanced networks may lead to a variety of mental disorders, such as depression and schizophrenia. Cortical GABAergic interneurons are categorized into many different subtypes according to their morphology, electrophysiological property and specific molecule. Majority of cortical GABAergic neurons are parvalbumin(PV) expressing and somatostatin(SOM) expressing neurons. We have studied the developmental changes of intrinsic and synaptic properties of the two subtype neurons, and the expression of glucocorticoid receptors on them using electrophysiology and immunohistochemistry. We found the marked enhancement in the firing rate of action potentials and excitatory synaptic activities in the first month after the birth, which may be due to the developmental increase in Kv3 potassium channels and formation of synapses respectively. These developmental changes may play an important role in maturation of neurons themselves and also homeostasis of networks. We also found that glucocorticoid receptors are richly expressed in both subtypes. Chronic stress induces a prolonged increase in the concentration of glucocorticoids which may affect the function of interneurons and damage homeostasis of neuronal network, leading to mental and neurological disorders. Our further study will explore these possible stress-related effects and the mechanisms, which will provide new targets for the development of novel therapies.
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