Cross-modal regulation of auditory cortex function

描述(申请人提供)：最近的研究强调，每个初级感觉皮质不是孤立工作的，而是有一定程度的相互作用，这不仅对多感觉整合至关重要，而且对于失去感觉通道时的感觉补偿也很重要。在盲人中，有几种跨模式补偿的报告，可以增强剩余的感官。虽然跨通道可塑性在很大程度上有利于盲人，但它阻碍了临床干预对功能的恢复。为 例如，据报道，人工耳蜗术后恢复语音识别的成功与否与跨模式可塑性的程度成反比。当盲人试图恢复视力时，很可能也会遇到类似的障碍。虽然有许多关于跨模式可塑性的研究，但大多数分析都是在系统神经科学的水平上进行的。因此，关于在细胞和电路层面上发生什么类型的变化的信息很少。我们先前的研究表明，剥夺啮齿动物的视力会增加初级视觉皮质(V1)的兴奋性突触传递，这与动态平衡适应是一致的。重要的是，我们还发现视觉剥夺减少了初级听觉皮质(A1)浅层的兴奋性突触传递。这些结果表明，失明可以跨模式改变其他初级感觉皮质的突触功能，但这些细胞水平的变化如何改变A1的神经元和回路功能尚不清楚。在目前的提案中，我们将检验我们的假设，即视觉剥夺诱导的突触可塑性改变A1区的功能电路和神经元感受场属性。为此，我们将确定视觉剥夺是否改变了A1特定兴奋和抑制回路的突触强度(目标1-1)和空间范围(目标1-2)。为了检验体内的后果，我们将检查视觉剥夺是否改变神经元的感受场属性(目标2-1)和A1中的群体编码(目标2-2)。我们的研究结果将对视觉剥夺如何改变A1的功能提供一个全面的机制理解。不同大脑区域之间的功能连接并不局限于感觉皮质。因此，我们的发现可以推广到解释神经元如何全局地适应对大脑其他部分的侮辱，例如在神经损伤、中风和神经退化期间发生的侮辱。

DESCRIPTION (provided by applicant): Recent studies highlight that each primary sensory cortex does not work in isolation, but have some degree of interaction, which is not only critical for multisensory integration, but also important for sensory compensation in the event of losing a sensory modality. In blind individuals, there are several reports of cross- modal compensation that allow enhancement of the remaining senses. While cross-modal plasticity is largely beneficial to blind individuals, it hinders the recovery of function by clinical interventions. For example, the success of recovering speech recognition following cochlear implants is reported to inversely correlate with the extent of cross-modal plasticity. It is likely that similar obstacls will be met when trying to restore vision in blind. While there are many studies on cross-modal plasticity, most analyses are done at the level of systems neuroscience. Therefore, there is scarce information as to what types of changes happen at the cellular and circuit level. We previously showed that depriving rodents of vision increases the excitatory synaptic transmission in primary visual cortex (V1), in line with homeostatic adaptation. Importantly, we also found that visual deprivation reduces the excitatory synaptic transmission in the superficial layers of primary auditory cortex (A1). These results suggest that losing vision can cross-modally alter synaptic function in other primary sensory cortices, but how these cellular level changes alter the neuronal and circuit function of A1 is unknown. In the current proposal, we will test our hypothesis that visual deprivation-induced synaptic plasticity alters the functional circuitry and the neuronal receptive field properties in A1. To do this, we will determine whether visual deprivation alters the synaptic strength (Aim 1-1) and spatial extent (Aim 1-2) of specific excitatory and inhibitory circuitry of A1. To examine the in vivo consequences, we will examine whether visual deprivation alters the receptive field properties of neurons (Aim 2-1) and the population encoding in A1 (Aim 2-2). Results from our study will provide a comprehensive mechanistic understanding of how visual deprivation changes the functionality of A1. Functional connectivity across different brain regions is not restricted to sensory cortices. Therefore, our findings can be generalized to elucidate how neurons globally adjust to insults to other parts of the brain, such as would occur during neural injury, stroke and neurodegeneration.