Cholinergic projection to the dorsal cap of the inferior olive of the rat, rabbit, and monkey

The inferior olive is divided into several subnuclei that receive specific sensory information. The caudal dorsal cap of the medial accessory subdivision of the inferior olive receives horizontal optokinetic information from the nucleus of the optic tract. The immediately subjacent b̃‐nucleus receives vertical vestibular information mediated by a GABAergic pathway originating from the ipsilateral descending and medial vestibular nuclei. None of the transmitters to the dorsal cap have been identified. Using choline acetyltransferase (ChAT) immunohistochemistry, we have identified a cholinergic pathway that terminates exclusively in the dorsal cap of rats and monkeys. No other division of the inferior olive received a significant cholinergic innervation. In the rabbit, immunostaining for ChAT reveals a weaker and more diffuse cholinergic innervation of both the dorsal cap and the subjacent b̃‐nucleus. In rats and rabbits we injected iontophoretically the orthograde tracer Phaseolus vulgaris leucoagglutinin (PHA‐L) into the medial and descending vestibular nuclei (MVN, DVN) as well as the nucleus prepositus hypoglossi (NPH) in order to trace the possible origin of the cholinergic projection. PHA‐L injections into the NPH and medial aspect of the MVN labeled terminals within the contralateral dorsal cap. PHA‐L injections in the central and lateral aspects of the MVN as well as the DVN labeled the ipsilateral b̃‐nucleus. Pressure injections of wheat germ agglutinin‐horseradish peroxidase (WGA‐HRP) in the caudal dorsal cap of the rabbit inferior olive demonstrated a predominantly contralateral projection to the dorsal cap from the lateral aspect of the NPH. However, pressure injections of HRP into the caudal dorsal cap combined with ChAT immunohistochemistry in the rabbit demonstrated that most of the neurons of the NPH that projected to the dorsal cap were not cholinergic, and that most of the ChAT‐positive neurons within the NPH occupied a more ventral location than the neurons within the NPH that were retrogradely labeled from the HRP injection into the contralateral dorsal cap. In the rat, we made lesions in the MVN, DVN and NPH by injection of ibotenic acid (0.3–0.5 m̈l), in an attempt to deplete the dorsal cap of the inferior olive of its cholinergic input. Lesions confined to the NPH and medial aspect of the MVN of the rat caused a loss of ChAT staining in the contralateral dorsal cap. Lesions placed more laterally within the MVN or DVN failed to deplete ChAT‐positive terminals in the contralateral or ipsilateral dorsal caps. The dorsal cap of the rat and monkey receives a discrete cholinergic projection. In the rat, this projection originates from the contralateral NPH. In the rabbit, the caudal inferior olive receives a weak cholinergic projection. The dorsal cap receives a projection from the contralateral NPH. However, this projection is mediated by a non‐cholinergic transmitter. © 1993 Wiley‐Liss, Inc.