INTRA-RETROSPLENIAL CORTICAL GRAFTS OF CHOLINERGIC NEURONS - FUNCTIONAL INCORPORATION AND RESTORATION OF HIGH-AFFINITY CHOLINE UPTAKE

Fetal septal neurons transplanted into the deafferented retrosplenial cortex (RSC) of rats have been shown to reinnervate the host brain and ameliorate spatial memory deficits. In the present study we examined the effects of implanting cholinergic neurons on high affinity choline uptake (HACU) in the denervated RSC and the correlational relationshi p between this cholinergic parameter and the level of behavioral recov ery. Three groups of animals were used: 1) normal control rats (NC), 2 ) rats with lesions of the fornix and cingulate pathways (FX), and 3) lesioned rats with fetal septal grafts in the RSC (RSCsep-TPL). We fou nd that intra-RSC septal grafts produced significant increases in HACU , and that recovery of HACU was significantly correlated with the impr ovements in the performance of spatial reference memory, spatial navig ation, and spatial working memory tasks. We have also investigated the ability of the host brain to modulate the activity of the implanted n eurons. In particular we evaluated the effect of the animals' performa nce in a 6-arm radial maze task on high affinity choline uptake (HACU) . Animals in each of the NC, FX, and RSCsep-TPL groups were randomly a ssigned one of the following subgroups: 1) rats that performed the maz e task before the determination of HACU (BEH), or 2) rats that did not perform the maze task before the determination of HACU (NON-BEH). Sig nificant increases were observed in the NC and RSCsep-TPL groups, but not in the FX animals, indicating that fetal septal grafts in the RSC can become functionally incorporated with the host neural circuitry, a nd that the activity of the implanted cholinergic neurons can be modul ated by the host brain.