Vertebrate gustatory systems include a tertiary ascending pathway from a secondary gustatory nucleus in the hindbrain to several forebrain nuclei. This connection is prominent in catfish, corresponding to their highly developed sense of taste. Iontophoretic injections of horseradish peroxidase were used to identify the specific target nuclei of the tertiary gustatory pathway in channel catfish and to characterize those nuclei by their respective connections. Efferents from the secondary gustatory nucleus (nGS) ascend in the tertiary gustatory tract to the caudal inferior lobe, where they terminate caudally in the nucleus lobobulbaris (nLB) and nucleus centralis (nCLI), and rostrally in the nucleus diffusus (nDLI). Secondary projections from the facial lobe (FL) also terminate in the nLB and in the nucleus subglomerulus (nSG). The nLB forms three cell groups (caudal--nLB, rostrolateral--rl nLB, parvicellular--nLBp), which project to the facial lobe, vagal lobe, and telencephalon, respectively. Cells from the nCLI project throughout the caudal inferior lobe and to the acousticolateral torus semicircularis and telencephalon, while the nDLI and nSG have intrinsic connections within the inferior lobe. The lateral thalamic nucleus projects from this region back to the nGS. Through these identified connections several mechanisms for the processing of gustatory information can be proposed. The descending projections from the nLB and nLT could provide feedback to the primary and secondary gustatory nuclei, and could modulate feeding-related motor circuits in the medulla. The connections of nCLI and nLBp with the telencephalon allow for the involvement of gustation in learning processes and other complex behaviors.

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High-titer, purified herpes simplex virus thymidine kinase (HSV-TK) retroviral particles, followed with intraperitoneal ganciclovir (GCV) were tested in Fischer rats bearing 1-week established 9L gliosarcomas. 9L cells were infused intracranially through a cannula on day 0, given intracranial infusions of HSV-TK retroviral particles on days 7-12, and given 5 or 10 daily doses of intraperitoneal GCV starting at day 14. Tumor volumetric studies performed on rat brains at day 26 after tumor infusion revealed significant differences in experimental groups receiving HSV-TK retroviral particles plus 10-day GCV or the 100% transduced 9L-TK group receiving GCV versus control groups treated with either buffer, HSV-TK vector, or either 5-or 10-day regimens of GCV alone. The duration of GCV administration and the volume of tumor burden influenced efficacy. Adjuvant dexamethasone did not significantly affect efficacy. Experiments in which 9L rechallenge of animals treated with 9L-TK/GCV or 9L tumors treated with HSV-TK vector/GCV indicated that a host immune response was involved in rejecting the rechallenge tumor. Outcome was dependent upon the site and size of the rechallenge inoculum. In vitro, bystander effects were significant but were especially marked when cell-to-cell contact was maintained. Cumulatively, the data indicate that both the bystander effect and the host immune response are responsible for the efficacy observed in the suicide gene therapy paradigm using purified HSV-TK retroviral particles and GCV to treat smaller tumor burden in rats with 9L gliosarcoma.

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