Global Synpatic Plasticity Mechanisms in Visual Cortex

项目摘要 虽然经验依赖的皮层可塑性在出生后早期发育中最为突出，但成年后， 大脑保持一定程度的可塑性。特别是初级感觉神经的表层突触 皮质，包括初级视觉皮质（V1），在整个成年期保持可塑性。我们先前报道 成年小鼠短时间的视觉剥夺或听觉剥夺会产生一种相当强烈的 V1的可塑性，这导致前馈和皮质内突触对主突触的不同可塑性。 神经元V1层2/3（L2/3）不仅接收来自视丘脑的前馈信息， （dLGN）通过L4，但它也接受来自其他皮质区域的皮质内反馈投射， 上下文到自下而上的视觉信息。我们发现，视觉剥夺优先增强皮质内 突触，而听觉剥夺导致成年V1的前馈回路增强。等 适应可能是盲人通过盲文阅读或言语激活V1的基础， 视觉处理报告在聋人科目。在这里，我们将研究这种电路级可塑性是如何 通过抑制回路募集的变化建立，以及它如何通过 前馈和皮层内输入。最近的研究表明，在招聘的短暂变化， 抑制回路在青少年大脑皮层的可塑性中起着重要作用。主要有两种不同的抑制性 V1中的回路，一个涉及小白蛋白（PV）中间神经元，另一个涉及生长抑素（SOM） 中间神经元。前者已被证明在介导视觉经验依赖中起着关键作用。 可塑性，而后者的目标是由自上而下的电路。在这里，我们将测试的假设，差异 PV和SOM回路的募集是视觉和听觉剥夺诱导的成人V1可塑性的基础。在 此外，我们假设由视觉或听觉剥夺引起的回路水平可塑性将导致 成人V1通过前馈和皮质内输入的差异激活。为了验证这些假设，我们将 确定成年V1 L2/3的PV和SOM回路的募集如何通过视觉与听觉进行可塑性 剥夺（目的1），以及V1激活模式如何从前馈输入（目的2）或长程皮层内 输入（目标3）在视觉或听觉剥夺后发生改变。我们的研究结果将提供急需的 成人V1可塑性的机制信息，并建议如何短暂的视觉或听觉剥夺， 来增强成人V1的独特功能。

Project Summary While experience-dependent cortical plasticity is most prominent during early postnatal development, the adult brain retains some level of plasticity. In particular, synapses in the superficial layers of primary sensory cortices, including the primary visual cortex (V1), remain plastic throughout adulthood. We previously reported that a short duration of visual deprivation or auditory deprivation in adult mice produces a rather robust plasticity in V1, which results in distinct plasticity of feedforward and intracortical synapses onto principal neurons. V1 layer 2/3 (L2/3) not only receives feedforward information transmitted from the visual thalamus (dLGN) through L4, but it also receives intracortical feedback projections from other cortical areas that provide context to bottom-up visual information. We found that visual deprivation preferentially potentiates intracortical synapses, while auditory deprivation leads to potentiation of the feedforward circuit in adult V1. Such adaptation might underlie activation of V1 by Braille reading or speech in blind individuals or enhancement of visual processing reported in deaf subjects. Here we will examine how such circuit-level plasticity is established by changes in recruitment of inhibitory circuits, and how it could alter activation of adult V1 through feedforward and intracortical inputs. Recent studies demonstrate that transient changes in the recruitment of inhibitory circuits play a role in enabling cortical plasticity in juveniles. There are largely two distinct inhibitory circuits in V1, one that involves parvalbumin (PV) interneurons and another that involves somatostatin (SOM) interneurons. The former has been shown to play a pivotal role in mediating visual experience-dependent plasticity, while the latter is targeted by top-down circuits. Here we will test the hypothesis that differential recruitment of PV and SOM circuits underlie adult V1 plasticity induced by visual and auditory deprivation. In addition, we hypothesize the circuit level plasticity induced by visual or auditory deprivation will lead to differential activation of adult V1 by feedforward and intracortical inputs. To test these hypotheses, we will determine how recruitment of PV and SOM circuits in adult V1 L2/3 undergo plasticity by visual versus auditory deprivation (Aim 1), and how V1 activation patterns from feedforward inputs (Aim 2) or long-range intracortical inputs (Aim 3) are altered following visual or auditory deprivation. Our results will provide much needed mechanistic information on adult V1 plasticity, and suggest how transient visual or auditory deprivation could be leveraged to enhance the distinct functionality of the adult V1.