PDF(Pubmed)
Abstract：
Astrocytes play a key role in the regulation of synaptic strength and are thought to orchestrate synaptic plasticity and memory. Yet, how specifically astrocytes and their neuroactive transmitters control learning and memory is currently an open question. Recent experiments have uncovered an astrocyte-mediated feedback loop in CA1 pyramidal neurons which is started by the release of endocannabinoids by active neurons and closed by astrocytic regulation of the D-serine levels at the dendrites. D-serine is a co-agonist for the NMDA receptor regulating the strength and direction of synaptic plasticity. Activity-dependent D-serine release mediated by astrocytes is therefore a candidate for mediating between long-term synaptic depression (LTD) and potentiation (LTP) during learning. Here, we show that the mathematical description of this mechanism leads to a biophysical model of synaptic plasticity consistent with the phenomenological model known as the BCM model. The resulting mathematical framework can explain the learning deficit observed in mice upon disruption of the D-serine regulatory mechanism. It shows that D-serine enhances plasticity during reversal learning, ensuring fast responses to changes in the external environment. The model provides new testable predictions about the learning process, driving our understanding of the functional role of neuron-glia interaction in learning.
摘要：
星形胶质细胞在突触强度的调节中起关键作用,并且被认为协调突触可塑性和记忆。然而，星形胶质细胞及其神经活性递质如何控制学习和记忆是目前一个悬而未决的问题。最近的实验发现了CA1锥体神经元中星形胶质细胞介导的反馈回路，该回路由活跃神经元释放内源性大麻素开始，并由星形胶质细胞调节树突上的D-丝氨酸水平封闭。D-丝氨酸是调节突触可塑性的强度和方向的NMDA受体的共激动剂。因此，由星形胶质细胞介导的活性依赖性D-丝氨酸释放是在学习过程中介导长期突触抑制（LTD）和增强（LTP）的候选者。这里,我们证明了这种机制的数学描述导致了与称为BCM模型的现象学模型一致的突触可塑性的生物物理模型。所得的数学框架可以解释在D-丝氨酸调节机制破坏后在小鼠中观察到的学习缺陷。它表明D-丝氨酸在反转学习过程中增强可塑性，确保对外部环境变化的快速反应。该模型提供了关于学习过程的新的可测试预测，推动我们对神经元-神经胶质相互作用在学习中的功能作用的理解。
