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.

A series of phenyl‐substituted N6‐phenyladenosines and N6‐phenyl‐5′‐N‐ethylcarboxamidoadenosines were synthesized and tested at adenosine receptor subtypes. EC50 values were determined for cyclic AMP production in CHO cells expressing human A2B receptors. Binding affinities were determined for rat A1 and A2A receptors and human A3 receptors. N6‐phenyladenosine displayed an EC50 value at A2B receptors of 6.3 μM. Several N6‐phenyladenosine derivatives were more active than N6‐phenyladenosine, while two analogs were also more potent than 5′‐N‐ethylcarboxamidoadenosine (NECA, 0.76 μM), i.e., the 4‐iodophenyl (10, 0.37 μM) and the 4‐aminosulfonylphenyl (20, 0.44 μM) derivatives. N6‐phenyl‐NECA derivatives were as active as their analogous adenosine derivatives. Drug Dev. Res. 49:85–93, 2000. © 2000 Wiley‐Liss, Inc.

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