Abstract
Neonatal stress and hippocampal long-term potentiation in freely moving adult rats
Marco Petrosino, GianPiero Pizzuti
Department of Neuroscience, University of Naples " Federico II ", Italy
The hippocampus, in the CNS, is a structure that play an important role in learning and memory. It is known to be especially vulnerable to the effect of stress. As the most of neurogenesis (for example, granular cells) and synaptogenesis occurs in the hippocampus in the early stages of post-natal life, then it would be interesting to study the adaptative responses to the effects of neonatal stress during the development. Stress-induced changes could have a profound impact on neural dentate function in hippocampus, represented by such plastic phenomenon as Long Term Potentiation (LTP). In a recent study, it has been determined that neonatal isolation significantly alters LTP measures in male and female juvenile (30 day old) rats and that there are gender-specific differences in these alterations. Our goal, was to determine if these effects of neonatal isolation endure even into adulthood freely moving rats (70-90 days old).
At birth, Sprague -Dawley rats were weighed, marked, and culled to 12 pups ( 6 male and 6 female) and randomly assigned to one of three treatment categories, isolated, non-isolated and unhandled. Over postnatal days 2-9 pups were isolated from the nest , dam and siblings for a period of 1 hr. Non-isolated siblings were returned to the nest with mother. At 70-90 days of age, animals were chronically implanted. Recording of a triphasic extracellular field potential at the level of the granular cells results by stimulation of the medial perforant path input. EPSP slope (a measure of synaptic activation) and PSA (population spike amplitude, a measure of the percent of the granule cell population discharging) were calculated from each recorded waveform. A baseline (pre-tetanization) input/output response curve was then constructed. A conditioning train of 500 msec. duration bursts of 400 Hz biphasic square wave stimulation (interburst interval = 5 sec.) was, then, applied to the perforant path. Changes in EPSP slope and PSA measures resulting from tetanization were assessed by recording ten responses to stimulation at 15 min., 30 min. and 1,3,5,18,24,48,72 and 96 hrs after tetanization . All values of EPSP slope and PSA were first subjected to a repeated measures MANOVA. For all statistics, F values returning p<0.05 were considered significant.
Post-tetanization potentiation occurred in both genders and in all treatment groups for both observed measures (EPSP slope and PSA). Results of the mean percent change of PSA in the male treatment groups demonstrated that: 1) all males returned to baseline levels in 96 hrs from tetanization, 2) the non-isolated males potentiated to a higher level than the isolated or the unhandled ( handling effect). In the females, for mean percent change PSA was noted that: the isolated females showed a significant difference in duration of potentiation (p<0.05) compared to the non-isolated and the unhandled. Between the genders, however, a significant, duration effect was observed (p<0.05).The isolated females returned to baseline after 1 week after tetanization while the isolated males only after 72 hrs from tetanization.
This study shows that a neonatal stressor could have an enduring impact on hippocampal function which can be observed in the adulthood and that the effect of neonatal stressor could be different between the genders.
