Facilitation of learning following injection of the chondroitin sulfate proteoglycan biglycan into the vicinity of the nucleus basalis magnocellularis

Abstract

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 nucleus basalis magnocellularis (NBM). In experiment 1, rats with chronically implanted cannulas were injected with biglycan and tested on the uphill avoidance task, which involves punishment of a high-probability turning response on a tilted platform (negative geotaxis). Immediately after the training trial, that is, after a tail-shock was administered upon performing the response, rats received one microinjection (0.5 μl) of substance P (SP) in a reference dosage of 0.74 pmol or biglycan (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 response. In experiment 2, a test for possible proactive effects of post-trial biglycan on performance during the retention trial was performed. Furthermore, the uphill avoidance task was combined with a conditioned place preference task to assess possible reinforcing effects of biglycan. Rats were injected with either 2.6 or 130.0 nmol biglycan immediately after the training trial of the uphill task. One control group received 2.6 nmol biglycan 5 h after the trial, a second group was sham-operated. 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 restricted quadrants of a circular open field (closed corral) for a single conditioning trial. When tested 24 h later on the uphill task, rats injected with 2.6 nmol biglycan again exhibited significantly longer uphill 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 biglycan on performance. Rats receiving biglycan or vehicle but no tail-shock showed poor retention performance on the uphill task. Subsequent tests for conditioned place preference in the open corral revealed that, unlike 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 region.