Excitation in neural circuits must be carefully controlled by inhibition to regulate information processing and network excitability. During development, cortical inhibitory and excitatory inputs are initially mismatched but become co-tuned or balanced with experience. However, little is known about how excitatory-inhibitory balance is defined at most synapses or about the mechanisms for establishing or maintaining this balance at specific set points. Here we show how coordinated long-term plasticity calibrates populations of excitatory-inhibitory inputs onto mouse auditory cortical pyramidal neurons. Pairing pre- and postsynaptic activity induced plasticity at paired inputs and different forms of heterosynaptic plasticity at the strongest unpaired synapses, which required minutes of activity and dendritic Ca²⁺ signaling to be computed. Theoretical analyses demonstrated how the relative rate of heterosynaptic plasticity could normalize and stabilize synaptic strengths to achieve any possible excitatory-inhibitory correlation. Thus, excitatory-inhibitory balance is dynamic and cell specific, determined by distinct plasticity rules across multiple excitatory and inhibitory synapses.

必须通过抑制来仔细控制神经回路中的励磁，以调节信息处理和网络的兴奋性。在发育过程中，皮层抑制性和兴奋性输入最初不匹配，但随着经验的变化而达到协调或平衡。但是，对于在大多数突触中如何定义兴奋性-抑制性平衡或在特定设定点建立或维持这种平衡的机制知之甚少。在这里，我们展示了如何协调长期可塑性来校准对小鼠听觉皮质锥体神经元的兴奋性抑制性输入。配对的突触前和突触后活动在配对输入处诱导可塑性，在最强的未配对突触处诱导不同形式的异突触可塑性，这需要几分钟的活动时间和树突状Ca ²⁺要计算的信令。理论分析表明，异突触可塑性的相对速率如何可以使突触强度正常化和稳定，从而实现任何可能的兴奋性-抑制性相关性。因此，兴奋性-抑制性平衡是动态的并且是细胞特异性的，由跨多个兴奋性和抑制性突触的独特可塑性规则确定。