Two to Tango: Joint dynamics of Excitatory and Inhibitory Synapses during Memory Formation

传统上，学习和记忆与突触的可塑性有关。最近的实验证据表明，GABA能突触的强度也可以修改的经验依赖性的方式。然而，抑制可塑性在记忆形成中的具体作用还没有得到很好的理解。最近的一项理论分析表明，记忆的形成和长期存储需要兴奋性和抑制性可塑性在多阶段过程中的紧密协同。特别是，抑制性突触可能不仅在记忆编码过程中控制兴奋性可塑性方面发挥作用，而且在支持长期记忆存储方面也发挥作用，因为它们具有比兴奋性突触大得多的存储容量。 在这里，我们建议测试这一假设相结合的慢性在体内成像的兴奋性和抑制性突触在小鼠的听觉皮层的背景下的联想记忆任务，与网络动力学的理论建模。此外，我们计划专门干扰兴奋性突触增强所必需的分子机制，以解开学习过程中兴奋性和抑制性突触可塑性的相互依赖关系。实验和理论建模的相互作用将为兴奋性和抑制性回路的可塑性如何参与学习和记忆过程提供新的见解，这可能是我们大脑最基本的功能。

Learning and memory have been traditionally associated to the plasticity of glutamatergic synapses. Recent experimental evidence indicates that GABAergic synaptic strength can also be modified in an experience-dependent manner. Yet, the specific role of inhibitory plasticity in the formation of memories is not well understood. A recent theoretical analysis suggests that the formation and long-term storage of memories require a tight co-orchestration of excitatory and inhibitory plasticity in a multi-stage process. In particular, inhibitory synapses may not only play a role in controlling excitatory plasticity during memory encoding, but also in supporting long-term memory storage as they have a storage capacity much larger than the excitatory synapses. Here, we propose to test this hypothesis by combining chronic in vivo imaging of excitatory and inhibitory synapses in the auditory cortex of mice in the context of an associative memory task, with theoretical modeling of network dynamics. Furthermore, we plan to interfere specifically with molecular mechanisms essential for the potentiation of excitatory synapses to disentangle the interdependencies of the plasticity of excitatory and inhibitory synapses during learning. This interplay of experiments and theoretical modeling will provide new insight on how plasticity of excitatory and inhibitory circuits participate in learning and memory processes, probably the most fundamental functions of our brains.