Critical periods are postnatal, restricted time windows of heightened plasticity in cortical neural networks, during which experience refines principal neuron wiring configurations. Here, we propose a model with two distinct types of synapses, innate synapses that establish rudimentary networks with innate function, and gestalt synapses that govern the experience-dependent refinement process. Nascent gestalt synapses are constantly formed as AMPA receptor-silent synapses which are the substrates for critical period plasticity. Experience drives the unsilencing and stabilization of gestalt synapses, as well as synapse pruning. This maturation process changes synapse patterning and consequently the functional architecture of cortical excitatory networks. Ocular dominance plasticity (ODP) in the primary visual cortex (V1) is an established experimental model for cortical plasticity. While converging evidence indicates that the start of the critical period for ODP is marked by the maturation of local inhibitory circuits, recent results support our model that critical periods end through the progressive maturation of gestalt synapses. The cooperative yet opposing function of two postsynaptic signaling scaffolds of excitatory synapses, PSD-93 and PSD-95, governs the maturation of gestalt synapses. Without those proteins, networks do not progress far beyond their innate functionality, resulting in rather impaired perception. While cortical networks remain malleable throughout life, the cellular mechanisms and the scope of critical period and adult plasticity differ. Critical period ODP is initiated with the depression of deprived eye responses in V1, whereas adult ODP is characterized by an initial increase in non-deprived eye responses. Our model proposes the gestalt synapse-based mechanism for critical period ODP, and also predicts a different mechanism for adult ODP based on the sparsity of nascent gestalt synapses at that age. Under our model, early life experience shapes the boundaries (the gestalt) for network function, both for its optimal performance as well as for its pathological state. Thus, reintroducing nascent gestalt synapses as plasticity substrates into adults may improve the network gestalt to facilitate functional recovery.

关键时期是皮质神经网络中可塑性增强的产后限制时间窗口，在此期间，经验完善了主要神经元的布线结构。在这里，我们提出了一种具有两种不同类型突触的模型，先天突触 建立具有先天功能的基本网络，以及 格式塔突触取决于经验的提炼过程。新生的格式塔突触作为AMPA受体沉默突触不断形成，是关键时期可塑性的基础。经验推动了格式塔突触的沉默和稳定以及突触修剪。这种成熟过程改变了突触模式，因此改变了皮层兴奋性网络的功能结构。初级视觉皮层（V1）中的眼优势可塑性（ODP）是皮质可塑性的已建立实验模型。尽管越来越多的证据表明，ODP关键时期的开始以局部抑制性回路的成熟为标志，但最近的结果支持了我们的模型，即关键时期通过完形性突触的逐步成熟而结束。兴奋性突触的两个突触后信号传递支架PSD-93和PSD-95的协同但相反的功能控制着格式塔突触的成熟。如果没有这些蛋白质，网络的发展就不会超出其固有功能，从而导致感知能力大大受损。虽然皮层网络在整个生命中都具有延展性，但其细胞机制，关键时期的范围和成人可塑性不同。关键时期ODP的开始是V1的视力下降，而成人ODP的特征是非视力的反应开始增加。我们的模型提出了针对关键时期ODP的基于格式塔突触的机制，并且基于该年龄新生的格式塔突触的稀疏性，还预测了成人ODP的不同机制。在我们的模式下 早期的生活经历塑造了网络功能的边界（格式塔），无论是其最佳性能还是病理状态。因此，将新生的格式塔突触作为可塑性底物重新引入成年人体内可以改善网络格式塔，以促进功能恢复。