Theta-frequency resonance at the cerebellum input stage improves spike timing on the millisecond time-scale

The neuronal circuits of the brain are thought to use resonance and oscillations to improve communication over specific frequency bands (Llinas, 1988; Buzsaki, 2006). However, the properties and mechanism of these phenomena in brain circuits remain largely unknown. Here we show that, at the cerebellum input stage, the granular layer (GRL) generates its maximum response at 5–7 Hz both in vivo following tactile sensory stimulation of the whisker pad and in acute slices following mossy fiber bundle stimulation. The spatial analysis of GRL activity performed using voltage-sensitive dye (VSD) imaging revealed 5–7 Hz resonance covering large GRL areas. In single granule cells, resonance appeared as a reorganization of output spike bursts on the millisecond time-scale, such that the first spike occurred earlier and with higher temporal precision and the probability of spike generation increased. Resonance was independent from circuit inhibition, as it persisted with little variation in the presence of the GABAA receptor blocker, gabazine. However, circuit inhibition reduced the resonance area more markedly at 7 Hz. Simulations with detailed computational models suggested that resonance depended on intrinsic granule cells ionic mechanisms: specifically, Kslow (M-like) and KA currents acted as resonators and the persistent Na current and NMDA current acted as amplifiers. This form of resonance may play an important role for enhancing coherent spike emission from the GRL when theta-frequency bursts are transmitted by the cerebral cortex and peripheral sensory structures during sensory-motor processing, cognition, and learning.