SPECIFICITY OF RABIES VIRUS AS A TRANSNEURONAL TRACER OF MOTOR NETWORKS - TRANSFER FROM HYPOGLOSSAL MOTONEURONS TO CONNECTED 2ND-ORDER AND HIGHER-ORDER CENTRAL-NERVOUS-SYSTEM CELL GROUPS

The specificity of transneuronal transfer of rabies virus [challenge v irus standard (CVS) strain] was evaluated in a well-characterized neur onal network, i.e., retrograde infection of hypoglossal motoneurons an d transneuronal transfer to connected (second-order) brainstem neurons . The distribution of the virus in the central nervous system was stud ied immunohistochemically at sequential intervals after unilateral ino culation into the hypoglossal nerve. The extent of transneuronal trans fer of rabies virus was strictly time dependent and was distinguished in five stages. At 1 day postinoculation, labelling involved only hypo glossal motoneurons (stage 1). Retrograde transneuronal transfer occur red from 2.0-2.5 days postinoculation (stage 2). In stages 2-4, differ ent groups of second-order neurons were labelled sequentially, dependi ng on the strength of their input to the hypoglossal nucleus. In stage s 4 and 5, labelling extended to several cortical and subcortical cell groups, which can be regarded as higher order because they are known to control tongue movements and/or to provide input to hypoglossal-pro jecting cell groups. The pattern of transneuronal transfer of rabies v irus resembles that of alpha-herpesviruses with regard to the nonsynch ronous labelling of different groups of second-order neurons and the t ransfer to higher order neurons. In striking contrast to alpha-herpesv iruses, the transneuronal transfer of rabies is not accompanied by neu ronal degeneration. Moreover, local spread of rabies from infected neu rons and axons to adjoining glial cells, neurons, or fibers of passage does not occur. The results show that rabies virus is a very efficien t transneuronal tracer. Results also provide a new insight into the or ganization of cortical and subcortical higher order neurons that media te descending control of tongue movements indirectly via hypoglossal-p rojecting neurons. (C) 1995 Wiley-Liss, Inc.