Spontaneous Infraslow Fluctuations Modulate Hippocampal EPSP-PS Coupling

Extensive trial-to-trial variability is a hallmark of most behavioral, cognitive, and physiological processes. Spontaneous brain activity (SBA), a ubiquitous phenomenon that coordinates levels and patterns of neuronal activity throughout the brain, may contribute to this variability by dynamically altering neuronal excitability. In freely-behaving male rats, we observed extensive variability of the hippocampal evoked response across 28-min recording periods despite maintaining constant stimulation parameters of the medial perforant path. This variability was related to antecedent SBA: increases in low-frequency (0.5–9 Hz) and high-frequency (40.25–100 Hz) band-limited power (BLP) in the 4-s preceding stimulation were associated with decreased slope of the field EPSP (fEPSP) and increased population spike (PS) amplitude. These fluctuations in SBA and evoked response magnitude did not appear stochastic but rather exhibited coordinated activity across infraslow timescales (0.005–0.02 Hz). Specifically, infraslow fluctuations in high- and low-frequency BLP were antiphase with changes in fEPSP slope and in phase with changes in PS amplitude. With these divergent effects on the fEPSP and PS, infraslow SBA ultimately modulates EPSP-PS coupling and thereby enables hippocampal circuitry to generate heterogeneous outputs from identical inputs. Consequently, infraslow SBA appears well suited to dynamically alter sensory selection and information processing and highlights the fundamental role of endogenous neuronal activity for shaping the brain’s response to incoming stimuli.