Ca²⁺-Independent Short-Term Depression in the Hippocampal CA1 Region

Ca²⁺ influx is usually considered a central trigger of neuronal plasticity, especially in mechanisms related to transmitter release and synaptic modification. However, plasticity may also involve mechanisms that do not require Ca²⁺ influx into neurons. We tested whether short-term plasticity can occur in the CA1 region of the mouse hippocampus under Ca²⁺-free conditions. In Ca²⁺-free artificial cerebrospinal fluid, in which synaptic transmission was not detected, local stimulation evoked a population potential in CA1, and theta-burst stimulation led to short-term depression during the stimulation protocol. This depression included three separable components: depression within bursts, cumulative depression of the first response across bursts, and enhancement of within-burst depression during repeated bursts. Whole-cell current-clamp recordings showed that the TBS stimulation protocol also changed action-potential kinetics at the level of individual neurons. These changes were expressed in CA1 pyramidal neurons as a reduction of maximum rise rate and slowing of repolarization, whereas stratum oriens interneurons did not show within-burst depression nor enhancement. Together, these data show that theta-burst stimulation can induce Ca²⁺-influx-independent short-term plasticity of action potentials in hippocampal CA1 pyramidal cells.