Synaptic plasticity induced by CA1 synaptic input with bursts superimposed on low-frequency rhythms

Abstract

Hippocampal neurons fire synchronously in a population at low frequencies and burst individually at high frequencies, with synaptic plasticity thought to depend on the interplay of these firing patterns. This study investigated synaptic plasticity in the hippocampal CA1 region induced by synaptic input with bursts superimposed on low-frequency rhythms. Low-frequency stimulation (LFS) was varied from 0.5 to 5 Hz, and various numbers of bursts (3–1000) consisting of 2–4 pulses at 100 Hz were superimposed on LFS. The patterned stimuli with 1-Hz LFS effectively induced synaptic plasticity. The direction and magnitude of plasticity depended on the number of bursts. We identified key roles for adenosine A₁ receptors and GABAergic signaling in regulating synaptic plasticity. The blockade of adenosine A₁ receptors increased the magnitude of long-term potentiation induced by specific burst patterns and differentially affected synaptic plasticity induced by 1-Hz LFS. Through its interactions with hippocampal rhythms and inhibitory circuits, adenosine elevated extracellularly during conditioning stimuli regulated the magnitude and direction of synaptic plasticity. This study proposes hypotheses for the role of adenosine in the modulation of synaptic plasticity, which maintains the balance between potentiation and depression in hippocampal circuits.