短暂视觉剥夺导致的视皮层神经微环路的变化的研究

It has been appreciated that visual experiences that occur early during the postnatal period, the time immediately following birth and when growth is most rapid, modifies the function of the visual cortex. Monocular deprivation (MD) for a few days during a critical period of early postnatal life clearly depresses the cortical responses to stimulation of the deprived eye, leading to amblyopia. The long-term depression (LTD) of excitatory intracortical synapses has been proposed as a general candidate mechanism for the weakening change of cortical responsiveness after short visual deprivation (short-MD). In addition, a former study by recording single synaptic connections reported that the decreased ability of the deprived eye to activate cortical neurons could be due to enhanced intracortical inhibition by markedly potentiating inhibitory feedback between fast-spiking basket cells and star pyramidal neurons. It was also shown that visual deprivation leaves excitatory connections in layer 4 (the primary input layer to cortex) unaffected. Combining these former studies, the intracortical synaptic networks seem non-uniformly changed following the short-MD procedure. We therefore generated a hypothesis: "The neuronal microcircuitry in visual cortex is changed by short-MD. The synaptic strength is not simply weakened but is rebalanced in the networks: The synaptic responses of single connections vary (enhanced or depressed or unchanged) depending upon the neuronal types, synapse types and their locations in the visual cortex. In order to understand the intracortical synaptic plasticity mechanisms that underlie the short-MD procedure，it is essential to carry out a systematic study to accurately record different types of neurons and synaptic connections formed between them. The proposed research plan aims to perform such a systematical study. Some promising preliminary results have been obtained.

出生后的关键期内短期单眼剥夺(short MD)导致视皮层发生特异变化，可最终导致弱视。长期以来认为皮层内兴奋性突触的长时程抑制(LTD)是视觉剥夺后皮层变化的主要机制。近期发现，短期视觉剥导致夺被剥夺眼皮层内抑制性突触活动的增强, 但并没有影响到第四层兴奋性突触联系的活动能力。因此，我们提出假说，"短暂视觉剥夺会使视皮层的神经微环路发生变化。神经网络中突触强度不是单一的弱化而是再平衡的过程: 神经元类型，突触类型以及它们在视皮层中的位置综合决定突触联系的变化性质（增强或抑制或者不变）"。为了验证这一假说进一步阐明短期单眼剥夺的皮层内可塑性变化的机制，我们从最基本和必要的研究着手, 精确地记录不同类型的神经元及其之间形成的突触联系，并已获得具有说服力的初步研究结果。该申请项目计划对视皮层的神经微环路进行系统精确的研究。其将对弱视的发病机制、治疗及预防产生重大意义

出生后的关键期内短期单眼剥夺(short MD)导致视皮层发生特异变化，可最终导致弱视。长期以来认为皮层内兴奋性突触的长时程抑制(LTD)是视觉剥夺后皮层变化的主要机制。近期发现，短期视觉剥导致夺被剥夺眼皮层内抑制性突触活动的增强, 但并没有影响到第四层兴奋性突触联系的活动能力。因此，我们提出假说，"短暂视觉剥夺会使视皮层的神经微环路发生变化。神经网络中突触强度不是单一的弱化而是再平衡的过程: 神经元类型，突触类型以及它们在视皮层中的位置综合决定突触联系的变化性质（增强或抑制或者不变）"。为了验证这一假说进一步阐明短期单眼剥夺的皮层内可塑性变化的机制，我们从最基本和必要的研究着手, 精确地记录不同类型的神经元及其之间形成的突触联系，并已获得具有说服力的初步研究结果。该申请项目计划对视皮层的神经微环路进行系统精确的研究。其将对弱视的发病机制、治疗及预防产生重大意义