Topsy Turvy: Functions of Climbing and Mossy Fibers in the Vestibulo-Cerebellum

Abstract

The cerebellum’s role in sensory-motor control and adaptation is undisputed. However, a key hypothesis pertaining to the function of cerebellar circuitry lacks experimental support. It is universally assumed that the discharge of mossy fibers accounts for modulation of Purkinje cell “simple spikes” (SSs). This assumption acts as a prism through which all other functions of cerebellar circuitry are viewed. The vestibulo-cerebellum (nodulus and uvula) receives a large, unilateral, vestibular primary afferent mossy fiber projection. We can test its role in modulating Purkinje cell SSs by recording the modulated activity of both mossy fiber terminals and Purkinje cell SSs evoked by identical natural vestibular stimulation. Sinusoidal rotation about the longitudinal axis (roll) modulates the activity of vestibular primary afferent mossy and climbing fibers as well as Purkinje cell SSs and complex spikes (CSs). Remarkably, vestibular primary afferent mossy fibers discharge 180 degrees out of phase with SSs. This indicates that mossy fibers cannot account for SS modulation unless an inhibitory synapse is interposed between mossy fibers or vestibular climbing fibers and Purkinje cells. The authors review several experiments that address the relative contributions of mossy and climbing fiber afferents to the modulation of SSs. They conclude that climbing fibers, not mossy fibers, are primarily responsible for the modulation of SSs as well as CSs and they propose revised functions for these two afferent systems.

Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats

“…In this case, only one final position in the DCN was visible. Therefore, we confirmed PC spiking activity from the presence of complex and simple spikes (Barmack and Yakhnitsa 2011;D'Angelo et al 2011;Miall et al 1998) (Fig. 5b).…”

The Expression Pattern of a Cav3-Kv4 Complex Differentially Regulates Spike Output in Cerebellar Granule Cells

“…By comparison, granule cells in the caudal cerebellum must respond to gradual increases or decreases in the frequency of MF input (Arenz et al, 2008). We note that distinctions of this nature are not absolute, as MF input reflecting tonic or burst activity has been reported in either region (Barmack and Yakhnitsa, 2008;Chadderton et al, 2014). Nonetheless, we chose these two very different forms of input as representative cases to test the hypothesis that a differential expression of the Cav3-Kv4 complex serves to shape the postsynaptic response in a manner that promotes efficient transfer of MF burst or tonic inputs.…”

Modulated discharge of Purkinje and stellate cells persists after unilateral loss of vestibular primary afferent mossy fibers in mice

“…2) SSs in folia 8 -9a are modulated by roll tilt even though these folia receive a nominal projection of vestibular primary and secondary mossy fiber afferents (Barmack et al 1993a;Barmack and Yakhnitsa 2012;Maklad and Fritzsch 2003). 3) Sinusoidal rotation about the vertical axis fails to modulate the discharge of SSs or CSs in folia 9c-10.…”

“…Folia 9c-10 receive the largest known singlesource mossy fiber projection from vestibular primary afferents that originate from ipsilateral labyrinth (Alley et al 1975;Barmack et al 1993a;Carpenter et al 1972;Gerrits et al 1989;Kevetter and Perachio 1986;Korte 1979;Maklad and Fritzsch 2003;Purcell and Perachio 2001;Voogd and Barmack 2005). Folia 8 -9a receive only a nominal vestibular primary or secondary afferent projection (Barmack et al 1993a;Barmack and Yakhnitsa 2012;Maklad and Fritzsch 2003), although they share with folia 9c-10 a large vestibular climbing fiber projection from the ␤-nucleus and dorsomedial cell column (DMCC) of the contralateral inferior olive (Alley et al 1975;Barmack and Yakhnitsa 2003;Fushiki and Barmack 1997;Groenewegen and Voogd 1977;Hoddevik and Brodal 1977;Schonewille et al 2006;Tan et al 1995;Voogd et al 1996;Voogd and Barmack 2005).…”

“…Golgi cells and unipolar brush cells also modulate the discharge of SSs indirectly by synaptically influencing the discharge of granule cells. The discharge of each of these interneurons is modulated by sinusoidal roll tilt (Barmack and Yakhnitsa 2008, 2011a, 2011bMathews et al 2012;Szapiro and Barbour 2007).…”