Operant Conditioning of Synaptic and Spiking Activity Patterns in Single Hippocampal Neurons
Operant Conditioning of Synaptic and Spiking Activity Patterns in Single Hippocampal Neurons
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DOI：
10.1523/jneurosci.5298-13.2014
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发表时间：
2014-04-02
影响因子：
5.3
通讯作者：
Ikegaya, Yuji
中科院分区：
文献类型：
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作者：
Ishikawa, Daisuke;Matsumoto, Nobuyoshi;Ikegaya, Yuji
学习是一个可塑性适应的过程，通过这个过程，神经回路会产生更好的结果。然而，在微观层面上，人们对突触活动如何形成所需的结构知之甚少。在这里，我们报告动物可以在海马体的特定神经元中产生特定形式的突触活动。在清醒、头部受限的小鼠中，当全细胞膜片钳 CA1 神经元表现出满足预设标准的自发突触活动时，我们对外侧下丘脑（与奖励相关的大脑区域）进行电刺激。 15 分钟内，小鼠学会频繁生成满足标准的兴奋性突触输入模式。对于抑制输入模式，没有观察到这种突触活动的强化学习。当突发单元活动模式在配对和非配对范例中进行调节时，突发尖峰事件的频率分别增加和减少。爆发强化发生在条件神经元中，但没有发生在其他相邻神经元中；然而，纹波场振荡也随之增强。神经调理取决于 NMDA 受体和多巴胺 D-1 受体的激活。强迫游泳的急性应激小鼠和抑郁模型小鼠未能表现出神经调节作用。这种学习缺陷通过重复使用抗抑郁药氟西汀治疗得以缓解。因此，内部动机的动物能够将持续的动作电位系列路由到海马网络的特定神经通路中。
Learning is a process of plastic adaptation through which a neural circuit generates a more preferable outcome; however, at a microscopic level, little is known about how synaptic activity is patterned into a desired configuration. Here, we report that animals can generate a specific form of synaptic activity in a given neuron in the hippocampus. In awake, head-restricted mice, we applied electrical stimulation to the lateral hypothalamus, a reward-associated brain region, when whole-cell patch-clamped CA1 neurons exhibited spontaneous synaptic activity that met preset criteria. Within 15 min, the mice learned to generate frequently the excitatory synaptic input pattern that satisfied the criteria. This reinforcement learning of synaptic activity was not observed for inhibitory input patterns. When a burst unit activity pattern was conditioned in paired and nonpaired paradigms, the frequency of burst-spiking events increased and decreased, respectively. The burst reinforcement occurred in the conditioned neuron but not in other adjacent neurons; however, ripple field oscillations were concomitantly reinforced. Neural conditioning depended on activation of NMDA receptors and dopamine D-1 receptors. Acutely stressed mice and depression model mice that were subjected to forced swimming failed to exhibit the neural conditioning. This learning deficit was rescued by repetitive treatment with fluoxetine, an antidepressant. Therefore, internally motivated animals are capable of routing an ongoing action potential series into a specific neural pathway of the hippocampal network.