Stability of neural circuit function

神经回路功能的稳定性

• 批准号: BB/N014561/1
• 负责人: Richard Baines
• 金额: $ 55.07万
• 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: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN014561%2F1
• 关键词: Stability; neural; circuit; function

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 how strongly they 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. It is, therefore, implicit that individual neurons have an inbuilt 'sense' of what is an appropriate level of activity. How such a reference-level develops and what the molecular components of the system are remains to be determined. We have identified a novel period in early neural circuit formation where manipulation of neural activity is sufficient to permanently change functional stability of mature neural circuits. We hypothesize that this period is required for the establishment of suitable activity-reference points that will form the foundation of on-going homeostatic mechanisms. 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，使我们能够学习新的任务或科普伤害和疾病。一个重要的变化领域是神经元暴露的兴奋量。所有的神经元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，称为突触，是高度动态的，可以迅速改变它们激活伙伴神经元的强度。当这些变化相加时，有可能使目标神经元缺乏兴奋，或者相反，饱和。任何一种极端都会使神经回路变得不稳定，并可能导致癫痫等疾病。为了防止这种极端情况，神经元已经发展出自我平衡机制，使它们能够调整对突触兴奋的反应。如果兴奋度太低，神经元会通过激发比正常数量更多的动作电位来提高输出。如果兴奋变得太大，这些神经元就会通过减少动作电位放电来做出反应。因此，这意味着单个神经元对什么是适当的活动水平具有内在的“感觉”。这样一个参考水平是如何发展的，以及系统的分子组成是什么，仍有待确定。我们已经确定了一个新的时期，在早期神经回路的形成，神经活动的操纵是足以永久改变成熟的神经回路的功能稳定性。我们假设，这段时间是建立合适的活动参考点，将形成持续的稳态机制的基础所必需的。我们的研究利用果蝇，因为它的基因组是完全测序的，因为它为人类神经系统提供了一个简单的模型。

项目成果

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

Characterization of Seizure Induction Methods in Drosophila.

• DOI: 10.1523/eneuro.0079-21.2021
• 发表时间: 2021-07-01
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Mituzaite, Jurga;Petersen, Rasmus;Baines, Richard A
• 通讯作者: Baines, Richard A

Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila.

• DOI: 10.1038/s41598-021-99868-8
• 发表时间: 2021-10-13
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Giachello CNG;Fan YN;Landgraf M;Baines RA
• 通讯作者: Baines RA

Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity.

• DOI: 10.1016/j.celrep.2017.09.004
• 发表时间: 2017-10-03
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Praschberger R;Lowe SA;Malintan NT;Giachello CNG;Patel N;Houlden H;Kullmann DM;Baines RA;Usowicz MM;Krishnakumar SS;Hodge JJL;Rothman JE;Jepson JEC
• 通讯作者: Jepson JEC

Electrophysiological Validation of Monosynaptic Connectivity between Premotor Interneurons and the aCC Motoneuron in the Drosophila Larval CNS

• DOI: 10.1523/jneurosci.2463-21.2022
• 发表时间: 2022-08-31
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Giachello, Carlo N. G.;Hunter, Iain;Baines, Richard A.
• 通讯作者: Baines, Richard A.