Conversion of graded presynaptic climbing fiber activity into graded postsynaptic Ca²⁺ signals by Purkinje cell dendrites

Abstract

The brain must make sense of external stimuli to generate relevant behavior. We used a combination of in vivo approaches to investigate how the cerebellum processes sensory-related information. We found that the inferior olive encodes contexts of sensory-associated external cues in a graded manner, apparent in the presynaptic activity of their axonal projections in the cerebellar cortex. Further, individual climbing fibers were broadly responsive to different sensory modalities but relayed sensory-related information to the cortex in a lobule-dependent manner. Purkinje cell dendrites faithfully transformed this climbing fiber activity into dendritewide Ca 2+ signals without a direct contribution from the mossy fiber pathway. These results demonstrate that the size of climbing fiber-evoked Ca 2+ signals in Purkinje cell dendrites is largely determined by the firing level of climbing fibers. This coding scheme emphasizes the overwhelming role of the inferior olive in generating salient signals useful for instructing plasticity and learning.2

The cerebellum encodes and influences the initiation and termination of discontinuous movements

“…In addition to the ramping of PC simple spiking, we observed an increase in climbing-fiber-evoked activity in a PC subpopulation, which preceded lick-bout initiation by ~100 ms. Although climbing fibers are responsive to sensory stimuli (Gaffield et al, 2019;Ohmae and Medina, 2015), the activity increase occurred in advance of exploratory licking bouts that were initiated without an overt sensory cue, ruling out the possibility that this activity represented an external stimulus. Climbing-fiber-evoked activity did not change at lick-bout termination, suggesting a specific role for this input only at the start of each movement cycle.…”

“…All two-photon imaging experiments were performed as previously described (Gaffield et al, 2016;Gaffield et al, 2019). Briefly, a custom-built, movable-objective microscope acquired continuous images at ~30 frame/s using an 8 kHz resonant scan mirror in combination with a galvanometer mirror (Cambridge Technologies, Bedford, MA).…”

Stochastic reaction-diffusion modeling of calcium dynamics in 3D dendritic spines of Purkinje cells

“…In Purkinje neurons, the IP 3 -induced Ca 2þ transients are dynamical responses to outer stimuli from PFs or CFs happening at low Ca 2þ concentrations. Whereas PFs are assumed to carry information about movement and fine motor control, CFs are assumed to carry error information that gives feedback about the network state that triggered the movement (86)(87)(88). We developed a model that is based on complex single-particle stochastic reaction and diffusion processes within a small three-dimensional geometry to study Ca 2þ transients in response to dynamical PF and CF stimuli.…”