Diet-induced alterations in the ontogeny of long-term potentiation.

Abstract

The ability of prenatally malnourished rats to establish and maintain long-term potentiation (LTP) of the perforant path/dentate granule cell synapse was examined in freely moving rats at 15, 30, and 90 days of age. Measures of the population EPSP slope and population spike amplitude (PSA) were calculated from dentate field potential recordings obtained prior to and at various times following tetanization of the perforant pathway. Significant enhancement of both population EPSP slope and PSA measures was obtained from all animals of both malnourished and well-nourished diet groups at 15 days of age. However, the magnitude of enhancement obtained from 15-day-old prenatally malnourished animals was significantly less than that of age-matched, well-nourished controls. At 30 days of age, PSA measures obtained from approximately 50% of prenatally malnourished 30-day-old rats showed no significant effect of tetanization, while measures obtained from the remaining 50% of these animals did not differ significantly from controls. EPSP slope measures for this age group followed much the same pattern, i.e., malnourished animals showing no significant enhancement of PSA measures exhibited only slight increases in EPSP slope beginning 1 h after tetanization and returned to baseline by 18 h post-tetanization. EPSP slope measures obtained from PSA-enhanced malnourished animals did not differ significantly from controls. At 90 days of age, PSA measures obtained from 50% of malnourished animals declined from pretetanization levels immediately following tetanization. Three hours after tetanization, however, this measure had increased to a level which did not differ significantly from that of the control group. PSA measures obtained from the remaining 50% of 90-day-old malnourished animals showed initial and sustained enhancement which did not differ significantly from those obtained from well-nourished age-matched controls. These results indicate that gestational protein malnutrition significantly affects the magnitude of tetanization-induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals) and significantly alters the time-course and magnitude of potentiation in approximately half of prenatally malnourished animals tested at 30 and 90 days of age. Given the primarily postnatal development of the dentate granule cells, these results may reflect malnutrition-induced delays in the neurogenesis and functional development of granule cells previously reported by our group. Most striking is the fact that significant impairments in LTP establishment were obtained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation commencing at birth is an intervention strategy incapable of ameliorating the effects of the gestational insult.