Activity-dependent changes in axonal action potential latency coordinated with synaptic potentiation in individual...

Neural plasticity enables the nervous system to adapt its structure and function in response to experience. Although synaptic plasticity is a central cellular mechanism underlying learning and memory, action potential propagation along axons is also subject to plastic regulation and critically shapes neural computation. However, how these distinct forms of plasticity are coordinated within individual neurons remains poorly understood. Here, we simultaneously monitored synaptic responses and antidromically evoked action potentials in hippocampal CA1 pyramidal neurons from male rats using whole-cell recordings. High-frequency stimulation reliably induced long-term potentiation (LTP) and was accompanied by a delayed yet transient reduction in antidromic action potential latency. The magnitude of latency shortening correlated with the degree of synaptic potentiation across multiple post-high-frequency stimulation time windows, including a late phase during which synaptic responses remained persistently elevated. Blocking the induction of LTP by intracellular Ca²⁺ chelation or NMDA receptor antagonism abolished latency shortening, indicating a dependence on LTP-related signaling pathways. Notably, the temporal profile of latency modulation depended on the site of axonal stimulation: latency shortening emerged earlier at proximal sites and was delayed at more distal sites, suggesting the propagation or accumulation of plasticity-related signals along an axon. Dual-site axonal stimulation within single neurons further demonstrated that action potential latency changes differed across axonal locations. Together, these findings demonstrate that synaptic potentiation is accompanied by spatially and temporally organized latency changes, revealing an additional layer of activity-dependent plasticity within individual neurons.Significance Statement Neuronal communication depends not only on the strength of synaptic transmission but also on the timing of action potential generation and arrival. Although synaptic plasticity has been studied extensively, it remains largely unknown whether action potential timing is dynamically regulated in association with synaptic plasticity. Here, we show that long-term synaptic potentiation in hippocampal neurons is accompanied by delayed, transient, and spatially organized changes in axonal action potential latency. These latency changes require NMDA receptor-dependent signaling and vary along axonal locations. Our findings reveal that synaptic plasticity can coordinate changes in synaptic strength with the timing of action potentials within individual neurons.