Rewiring cortex using inhibitory neuron transplantation

描述(由申请人提供)：使用抑制性神经元移植重新连接大脑皮质童年经历塑造了我们的感知和行为。与成年人相同的经历几乎没有什么效果。在青年的知觉和行为可塑性的背后，是年轻大脑重新连接的明显能力。抑制性中间神经元在促进幼年视皮层的可塑性方面发挥着积极的作用。我们最近发现，移植抑制性中间神经元可以重新激活视皮层的可塑性。在这个提案中，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。我们之前发现，移植的抑制性神经元与宿主大脑建立了直接的突触连接。我们建议使用视觉反应的体内钙成像和体内光遗传刺激来研究移植的抑制性神经元与宿主视皮层细胞之间的输入和输出联系。我们的假设是，移植的细胞在宿主大脑中增加了一种可变抑制模式，使视觉皮质中现有的连接更快地适应感觉体验的变化。我们还建议研究当移植到完全成年的大脑中时，抑制神经元移植是否重新激活可塑性。使用移植对成人大脑皮质进行治疗性重新连接将代表着一条扭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措施，通过重新激活内源性抑制神经元中休眠的发育程序来促进大脑可塑性。

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.