Selective Impairment of the Cerebellar C1 Module Involved in Rat Hind Limb Control Reduces Step-Dependent Modulation of Cutaneous Reflexes

Abstract

The cerebellum is divided into multiple parasagittally organized modules, which are thought to represent functional entities. How individual modules participate in cerebellar control of complex movements such as locomotion remains largely unknown. To a large extent, this is caused by the inability to study the contribution of individual modules during locomotion. Because of the architecture of modules, based on narrow, elongated cortical strips that may be discontinuous in the rostrocaudal direction, lesion of a complete module, without affecting neighboring modules, has not been possible. Here, we report on a new method for inducing a selective dysfunction of spatially separated parts of a single module using a small cortical injection of a retrogradely transported neurotoxin, cholera toxin b-subunit-saporin. We show that such a local injection into the C1 module results in climbing fiber and partial mossy fiber deafferentation of functionally related areas of this module, thereby resulting in a severe impairment of the whole module without affecting neighboring modules. A subsequent functional analysis indicates that such an impairment of the hindlimb part of the C1 module did not have a significant impact on skilled walking or overall stepping pattern. However, the modulation of cutaneously induced reflexes during stepping was severely diminished. We propose that the C1 module is specifically involved in the adaptive control of reflexes.

Cerebellar Modules: Individual or Composite Entities?

“…These findings differ from those in a recent study (Pijpers et al, 2008) that used an alternative approach in rats. Instead of chemically inactivating the olive, these authors cortically injected the retrogradely transported neurotoxin cholera toxin b conjugated to saporin to induce selective dysfunction of a complete module without affecting neighboring modules.…”

“…Instead of chemically inactivating the olive, these authors cortically injected the retrogradely transported neurotoxin cholera toxin b conjugated to saporin to induce selective dysfunction of a complete module without affecting neighboring modules. Pijpers et al (2008) demonstrated that selective impairment of the C1 hindlimb module in the rat did not lead to any recognizable defects during locomotion. However, the step phase-dependent modulation of cutaneously induced reflexes during locomotion was significantly reduced (Pijpers et al, 2008, their Fig.…”

“…Pijpers et al (2008) demonstrated that selective impairment of the C1 hindlimb module in the rat did not lead to any recognizable defects during locomotion. However, the step phase-dependent modulation of cutaneously induced reflexes during locomotion was significantly reduced (Pijpers et al, 2008, their Fig. 7B) compared with that in control animals.…”

Organization of Cerebral Projections to Identified Cerebellar Zones in the Posterior Cerebellum of the Rat

“…As the cerebellum consists of parasagittal zones that define fundamental modules of neural processing and each zone receives input from a distinct subdivision of the IO, neuronal labeling with RV/CTb within the IO was used to determine the actual place and spread of the injection in terms of zonal organization as reported by Voogd and collaborators (Voogd et al, 2003;Voogd and Ruigrok, 2004;Pijpers et al, 2008). The relevant zones in the posterior cerebellum and the olivary areas that form the origin of the climbing fibers to these zones are shown in Figure 1E.…”

Establishment of topographic circuit zones in the cerebellum of scrambler mutant mice

“…The cerebellum is organized into an array of sagittal zones that control sensory-motor behavior (Seoane et al, 2005; Pijpers et al, 2008; Apps and Hawkes, 2009; Horn et al, 2010; Cerminara and Apps, 2011). Zones are best revealed by the expression patterns of genes and proteins in Purkinje cells (Apps and Hawkes, 2009; White et al, 2012; White and Sillitoe, 2013).…”