We ex the axonal transport of two strain of herpes simplex virus 1 (HSV-1) within the central nervous system ofcebus monkeys. Each strain was inijected into the "arm area" of the primry motor cortex. One strain, HSV-1(McIntyre-B), was transported transneuronaly in the retrograde direction. It infected neurons at sites known to project to the arm area of the primary motor cortex (e.g., ventrolateral thalamus). In addition-, "second-order" neurons were labeled in the deep cerebellar nuclei (dentate and interpositus) and in the globus pallidus (internal s ). This result supports the concept that the arm area of the primary motor cortex is a target of both cerebellar and basal ganglia output. In contrast, the other strain, HSV-1(H129), was transported transneuronally in the anterograde direction. It infected neurons at sites known to receive input from the arm area of the primary motor cortex (e.g., putamen, pontine nuclei). In addition, "third-order" neurons were labeled in the cerebellar cortex (granule and Golgi celis) and in the globus paldus (largely the external segment). Our observations suggest that strain differences have an important impact on the direction of transneuronal transport of HSV-1. Furthermore, it should be possible to examine the organization of cerebeflar and basal ganglia loops with cerebral-cortex by exploiting tusneuronal transport of HSV-1 and virus strain differences.Part .of the neural substrate for the central control of movement in primates is formed by multiple "loops" between the cerebral cortex and two subcortical centers, the basal ganglia and the cerebellum. These circuits are thought to be involved in many aspects of motor behavior, including the programming, initiation, and regulation of limb movement (e.g., refs. 1-4). In recent experiments, we have begun to explore the structure of these loops by using transneuronal transport of herpes simplex virus 1 (HSV-1). In the course of these studies, we made the surprising observation that the direction of transneuronal transport within these circuits depends on the specific strain of HSV-1 inoculated into the animal. To illustrate this result, in this report we describe some of the patterns of transneuronal-transport of two strains of HSV-1 within the pathways that link the "arm area" of the primary motor cortex with the basal ganglia and cerebellum.
MATERIALS AND METHODSEither the H129 strain (5) (1.5 x 1012 plaque-forming units (pfu)/ml, n = 2; 8.0 x 1010 pfu/ml, n = 1) or the McIntyre-B strain (6) (6.1 x 10P pfu/ml, n = 2) ofHSV-1 was injected into the left arm area of the primary motor cortex (7) of cebus monkeys (Cebus apella). Each animal was anesthetized with ketamine (10 mg/kg, i.m.) and Nembutal (sodium pentobarbital, 25 mg/kg, i.p.), and 0.05 jul of virus was injected at each of six cortical sites. The surgical procedures used have been described in detail (8,9). The injection sites included both the crest of the precentral gyrus and the anterior bank of the central sulcus. Two to three days after inoculation, anima...
