Abstract
Excitation in neural circuits must be carefully controlled by inhibition to regulate information processing and network excitability. During development, inhibitory and excitatory inputs in the cerebral cortex are initially mismatched but become co-tuned or ‘balanced’ with experience. However, little is known about the set-points for excitatory-inhibitory balance or the mechanisms for establishing or maintaining this balance. Here we show how coordinated long-term synaptic modifications calibrate populations of excitatory and 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 amount 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.
One-Sentence Abstract Heterosynaptic plasticity can rapidly and specifically balance inhibition with excitation across multiple inputs onto cortical pyramidal neurons.