Beyond “all-or-nothing” climbing fibers: graded representation of teaching signals in Purkinje cells

Abstract

Arguments about the function of the climbing fiber (CF) input to the cerebellar cortex have fueled a rabid debate that started over 40 years ago, and continues to polarize the field to this day. The origin of the controversy can be traced back to 1969, the year David Marr published part of his dissertation work in a paper entitled “A theory of cerebellar cortex.” In Marr’s theory, CFs play a key role during the process of motor learning, providing an instructive signal that serves as a “teacher” for the post-synaptic Purkinje cells. Although this influential idea has found its way into the mainstream, a number of objections have been raised. For example, several investigators have pointed out that the seemingly “all-or-nothing” activation of the CF input provides little information and is too ambiguous to serve as an effective instructive signal. Here, we take a fresh look at these arguments in light of new evidence about the peculiar physiology of CFs. Based on recent findings we propose that at the level of an individual Purkinje cell, a graded instructive signal can be effectively encoded via pre- or post-synaptic modulation of its one and only CF input.

Inferior Olivary TMEM16B Mediates Cerebellar Motor Learning

“…The correlation between reduced IO excitability and impaired cerebellar motor learning in TMEM16B KO mice adds new evidence to support the theory that IO excitability and the subsequent climbing fiber impulses play a key role on the formation of cerebellar motor learning (Lang et al, 2017; Najafi and Medina, 2013). The prevailing view of cerebellar motor learning is that IO neurons relay movement error signals through climbing fiber spikes to cause synaptic modification in the cerebellar cortex, such as long-term depression (LTD) of parallel fiber to Purkinje cell synapses (Lang et al, 2017).…”

Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior

“…It has been reported that γ-7 is enriched in the postsynaptic density (PSD) (12,14) and associated with PSD-95, although it lacks a typical PDZ binding motif on its C-tail (12). Our results suggested that γ-7 presumably interacts with PSD proteins, and the maintenance of intact cf fiber input through multiple mechanisms may represent an important compensatory strategy for preserving a key instructive signal in motor learning (30,31). Together, our results show that γ-2 and γ-7 TARP subunits are required for AMPARmediated cf input onto PCs and that this excitatory input is necessary for the proper control of motor function and coordination involved in the behaviors examined.…”

Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model

“…This means that a suppression of Purkinje cell activity is sufficiently strong to suppress the signal generated by a periorbital US. However, these results do not contradict the idea that the nucleo-olivary inhibition can change the olivary signal in a graded manner, such as by reducing the number of spikes in the climbing-fiber signal (15,(43)(44)(45). We also hypothesized that, when each CS induced a suppression of the simple spike activity, presentation of a compound CS would result in an even lower probability of a complex spike following the periorbital US.…”