Rewiring cortex using inhibitory neuron transplantation

使用抑制性神经元移植重新连接皮质

• 批准号: 8571570
• 负责人: Sunil Gandhi
• 金额: $ 231万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8571570
• 关键词: Adolescent; Adult; Behavior; Behavioral; Brain; Brain Injuries; Calcium; Cell Transplants; Cells; Childhood; Development; Image; Implant; Interneurons; Intervention; Molecular; Output; Pattern; Perception; Play; Research; Role; Sensory; Shapes; Synapses; Therapeutic; Transplantation; Visual; Visual Cortex; Youth; experience; in vivo; inhibitory neuron; insight; novel; optogenetics; programs; response

DESCRIPTION (provided by applicant): Rewiring cortex using inhibitory neuron transplantation Childhood experiences shape our perceptions and behaviors. The same experiences as adults have little effect. Underlying the perceptual and behavioral malleability of youth is the pronounced capacity of the young brain to be rewired. One class of neurons, inhibitory interneurons, has been shown to play an active role in promoting the plasticity of the juvenile visual cortex. We recently discovered that transplantation of inhibitory interneurons reactivates plasticity in the visual cortex. In this proposal, we will use inhibitory neuron transplantation to gain insight into the mechanisms of cortical plasticity. We found previously that transplanted inhibitory neurons made direct synaptic connections with the host brain. We propose using in vivo calcium imaging of visual responses and in vivo optogenetic stimulation to study the input and output connections made by transplanted inhibitory neurons with cells in the host visual cortex. Our hypothesis is that transplanted cells add a pattern of variable inhibition o the host brain that makes existing connections in the visual cortex quicker to adapt to changes in sensory experience. We also propose to investigate whether the transplantation of inhibitory neurons reactivates plasticity when implanted into the fully adult brain. Therapeutic rewiring of adult cortex using transplantation would represent an entirely new avenue for reversing brain damage. Eventually, this research program may identify novel molecular interventions that promote brain plasticity by reactivating dormant developmental programs in endogenous inhibitory neurons.

描述（由申请人提供）：使用抑制性神经元移植重新连接皮层童年经历塑造了我们的感知和行为。与成年人一样的经历几乎没有影响。年轻人的感知和行为可塑性的基础是年轻人的大脑具有明显的重新连接能力。其中一类神经元，抑制性中间神经元，已被证明在促进青少年视皮层的可塑性方面起着积极的作用。我们最近发现，抑制性中间神经元的移植重新激活了视觉皮层的可塑性。在本提案中，我们将使用抑制性神经元移植来深入了解皮质可塑性的机制。我们以前发现移植的抑制性神经元与宿主大脑建立了直接的突触连接。我们建议使用在体内钙成像的视觉反应和在体内光遗传学刺激研究的输入和输出的连接移植的抑制性神经元细胞在宿主的视觉皮层。我们的假设是，移植的细胞在宿主大脑中增加了一种可变的抑制模式，使视觉皮层中现有的连接更快地适应感官体验的变化。我们还建议研究是否抑制性神经元移植重新激活可塑性时，植入到完全成人的大脑。利用移植对成年人大脑皮层进行治疗性重新布线将代表一种逆转脑损伤的全新途径。最终，这项研究计划可能会确定新的分子干预，通过重新激活内源性抑制神经元中的休眠发育程序来促进大脑可塑性。

项目成果

Precocious deposition of perineuronal nets on Parvalbumin inhibitory neurons transplanted into adult visual cortex.

• DOI: 10.1038/s41598-018-25735-8
• 发表时间: 2018-05-10
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bradshaw KP;Figueroa Velez DX;Habeeb M;Gandhi SP
• 通讯作者: Gandhi SP

Inhibitory Neuron Transplantation into Adult Visual Cortex Creates a New Critical Period that Rescues Impaired Vision.

• DOI: 10.1016/j.neuron.2015.03.062
• 发表时间: 2015-05-20
• 期刊: NEURON
• 影响因子: 16.2
• 作者: Davis, Melissa F.;Velez, Dario X. Figueroa;Guevarra, Roblen P.;Yang, Michael C.;Habeeb, Mariyam;Carathedathu, Mathew C.;Gandhi, Sunil P.
• 通讯作者: Gandhi, Sunil P.