Spontaneous Infraslow Fluctuations Modulate Hippocampal EPSP-PS Coupling

Abstract

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 (0.5-9Hz), and high (40.25-100Hz), frequency band-limited power (BLP) in the 4s preceding stimulation were associated with decreased slope of the field excitatory postsynaptic potential (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 (0.005-0.02Hz). 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.

Significance Statement The brain’s response to a given input is variable and enables flexible responses based on past experience and/or current needs. Widespread, dynamic, and ever-present, spontaneous brain activity may contribute to response heterogeneity by altering endogenous brain states to modulate subsequent processing of exogenous information. We investigated how spontaneous activity could mechanistically alter information processing by assessing its role in modulating the brain’s response to electrically-evoked activation. We find very slow fluctuations in spontaneous activity affect evoked-response variability by altering the coupling of neuronal input (i.e. depolarization) to subsequent neuronal output (i.e. action potential generation). These results, therefore, characterize a broad mechanism by which spontaneous brain activity can alter sensory and information processing.