Glycinergic Inhibitory Plasticity in Binaural Neurons Is Cumulative and Gated by Developmental Changes in Action Potential Backpropagation

Utilization of timing-based sound localization cues by neurons in the medial superior olive (MSO) depends critically on glycinergic inhibitory inputs. After hearing onset, the strength and subcellular location of these inhibitory inputs are dramatically altered, but the cellular processes underlying this experience-dependent refinement are unknown. Here we reveal a form of inhibitory long-term potentiation (iLTP) in MSO neurons that is dependent on spiking and synaptic activation but is not affected by their fine-scale relative timing at higher frequencies prevalent in auditory circuits. We find that iLTP reinforces inhibitory inputs coactive with binaural excitation in a cumulative manner, likely well suited for networks featuring persistent high-frequency activity. We also show that a steep drop in action potential size and backpropagation limits induction of iLTP to the first 2 weeks of hearing. These intrinsic changes would deprive more distal inhibitory synapses of reinforcement, conceivably establishing the mature, soma-biased pattern of inhibition. •Inhibitory glycinergic inputs to MSO neurons undergo long-term potentiation•iLTP requires NMDAR-mediated calcium influx and action potential firing•iLTP is proportional to stimulus frequency and number but not fine-scale timing•iLTP is gated developmentally by reductions in action potential backpropagation Winters et al. demonstrate a mechanism for reinforcement of inhibitory inputs that are coactive with excitatory inputs in a brainstem circuit critical for sound localization, and this plasticity is gated developmentally by the progressive decline of action potential backpropagation.