FACILITATION OF LEARNING FOLLOWING INJECTION OF THE CHONDROITIN SULFATE PROTEOGLYCAN BIGLYCAN INTO THE VICINITY OF THE NUCLEUS BASALIS MAGNOCELLULARIS

The aim of this study was to examine the effects of biglycan, a small chondroitin sulfate proteoglycan with neurotrophic activity, on memory and reinforcement upon unilateral injection into the region of the nu cleus basalis magnocellularis (NBM). In experiment 1, rats with chroni cally implanted cannulas were injected with biglycan and tested on the uphill avoidance task, which involves punishment of a high-probabilit y turning response on a tilted platform (negative geotaxis). Immediate ly after the training trial, that is, after a tail-shock was administe red upon performing the response, rats received one microinjection (0. 5 mu l) of substance P (SP) in a reference dosage of 0.74 pmol or bigl ycan (doses ranging from 1.3 to 1300.0 nmol) into the NBM region. When tested 24 h later, rats treated with SP (0.74 pmol) or biglycan (2.1 and 2.6 nmol) had significantly longer uphill latencies than vehicle ( PBS) controls, indicative of superior learning of the avoidance respon se. In experiment 2, a test for possible proactive effects of post-tri al biglycan on performance during the retention trial was performed. F urthermore, the uphill avoidance task was combined with a conditioned place preference task to assess possible reinforcing effects of biglyc an. Rats were injected with either 2.6 or 130.0 nmol biglycan immediat ely after the training trial of the uphill task. One control group rec eived 2.6 nmol biglycan 5 h after the trial, a second group was sham-o perated. Additional groups were included which received biglycan (2.6 or 130.0 nmol), SP (0.74 pmol) or PBS after the training trial but no tail-shock. After training these rats were placed into one of four res tricted quadrants of a circular open field (dosed corral) for a single conditioning trial. When tested 24 h later on the uphill task, rats i njected with 2.6 nmol biglycan again exhibited significantly longer up hill latencies than did vehicle-injected rats. Retention latencies for the rats of the biglycan 5-h delay group did not differ from those of the vehicle-injected animals, ruling out proactive effects of biglyca n on performance. Rats receiving biglycan or vehicle but no tail-shock showed poor retention performance on the uphill task. Subsequent test s for conditioned place preference in the open corral revealed that, u nlike SP, injection of biglycan had no positively reinforcing effects upon injection into the NBM. In summary, these findings indicate that biglycan facilitates memory processing when injected into the NBM regi on.