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

学习和记忆传统上与谷氨酸能突触的可塑性有关。最近的实验证据表明，GABA能突触强度也可以以经验依赖的方式改变。然而，抑制可塑性在记忆形成中的具体作用还没有被很好地理解。最近的一项理论分析表明，记忆的形成和长期存储需要多阶段过程中兴奋性和抑制性可塑性的紧密协调。特别是，抑制性突触不仅在记忆编码过程中控制兴奋性可塑性，而且由于它们的存储容量比兴奋性突触大得多，还可能在支持长期记忆存储方面发挥作用。在这里，我们建议在联想记忆任务的背景下，通过将小鼠听觉皮质兴奋性和抑制性突触的慢性活体成像与网络动力学的理论建模相结合来检验这一假说。此外，我们计划专门干预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突触和抑制性突触可塑性的相互依赖关系。这种实验和理论建模的相互作用将为兴奋和抑制电路的可塑性如何参与学习和记忆过程提供新的见解，学习和记忆过程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.