Homeostatic control of neuron excitability

神经元兴奋性的稳态控制

• 批准号: BB/L027690/1
• 负责人: Richard Baines
• 金额: $ 50.86万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL027690%2F1
• 关键词: Homeostatic; control; neuron; excitability

The nervous system must adapt and change to allow us to learn new tasks or to cope with injury and disease. One significant area of change is the amount of excitation neurons are exposed to. All neurons become 'wired' together in circuits that control our behaviours and potential to learn. These connections, termed synapses, are highly dynamic and can rapidly change their ability to either inhibit or activate partner neurons. These changes, when summed, have the potential to either leave a target neuron devoid of excitation or, by contrast, saturated. Either extreme can push neural circuits towards destabilisation and may result in diseases such as epilepsy. To guard against such extremes, neurons have developed homeostatic mechanisms to allow them to adjust how they respond to synaptic excitation. If excitation becomes too low, neurons boost their output by firing more than normal numbers of action potentials. If excitation becomes too great, these same neurons respond by reducing their action potential firing. Although well established, our understanding of the underlying components of homeostatic mechanisms is poor. Our studies utilise the fruitfly because its genome is fully sequenced and because it provides a simple model for the human nervous system.

神经系统必须适应和改变，以便我们能够学习新任务或应对伤害和疾病。一个重要的变化是暴露于兴奋神经元的数量。所有神经元都在控制我们的行为和学习潜力的电路中“连接”在一起。这些连接被称为突触，是高度动态的，可以迅速改变它们抑制或激活伙伴神经元的能力。这些变化加起来有可能使目标神经元失去兴奋，或者相反，使目标神经元饱和。任何一种极端都会使神经回路不稳定，并可能导致癫痫等疾病。为了防止这种极端情况，神经元已经发展出稳态机制，使它们能够调整对突触兴奋的反应。如果兴奋变得太低，神经元会通过激发超过正常数量的动作电位来提高其输出。如果兴奋变得太大，这些相同的神经元会通过减少动作电位放电来做出反应。尽管已经很成熟，但我们对稳态机制的基本组成部分的了解还很有限。我们的研究利用果蝇，因为它的基因组已完全测序，并且它为人类神经系统提供了一个简单的模型。

项目成果

Targeting neuronal homeostasis to prevent seizures

• DOI: 10.1101/2022.03.07.483229
• 发表时间: 2022-03
• 期刊: bioRxiv
• 作者: Fred Mulroe;Wei-Hsiang Lin;Connie Mackenzie-Gray Scott;Najat Aourz;Yuen Ngan Fan;Graham A. Coutts;R. R. Parrish-R.;I. Smolders;A. Trevelyan;Robert Wykes;S. Allan;Sally Freeman;R. Baines

An intestinal zinc sensor regulates food intake and developmental growth.

• DOI: 10.1038/s41586-020-2111-5
• 发表时间: 2020-04
• 期刊: Nature
• 影响因子: 64.8
• 作者: Redhai S;Pilgrim C;Gaspar P;Giesen LV;Lopes T;Riabinina O;Grenier T;Milona A;Chanana B;Swadling JB;Wang YF;Dahalan F;Yuan M;Wilsch-Brauninger M;Lin WH;Dennison N;Capriotti P;Lawniczak MKN;Baines RA;Warnecke T;Windbichler N;Leulier F;Bellono NW;Miguel-Aliaga I
• 通讯作者: Miguel-Aliaga I

Targeting firing rate neuronal homeostasis can prevent seizures.

• DOI: 10.1242/dmm.049703
• 发表时间: 2022-10-01
• 期刊: Disease models & mechanisms
• 影响因子: 4.3

Seizure control through genetic and pharmacological manipulation of Pumilio in Drosophila: a key component of neuronal homeostasis.

• DOI: 10.1242/dmm.027045
• 发表时间: 2017-02-01
• 期刊: Disease models & mechanisms
• 影响因子: 4.3
• 作者: Lin WH;Giachello CN;Baines RA
• 通讯作者: Baines RA

An RNAi-mediated screen identifies novel targets for next-generation antiepileptic drugs based on increased expression of the homeostatic regulator pumilio.

• DOI: 10.1080/01677063.2018.1465570
• 发表时间: 2018-03
• 期刊: Journal of neurogenetics
• 影响因子: 1.9
• 作者: Lin WH;He M;Fan YN;Baines RA
• 通讯作者: Baines RA