Neonatal Isolation Enhances Hippocampal Dentate Response to Tetanization in Freely Moving Juvenile Male Rats

The impact of early neonatal isolation on measures of hippocampal neuronal plasticity was examined in freely moving male rats at 30 days of age. Beginning on Postnatal (PN) Day 2, one-half of pups from each experimental litter were individually isolated from the nest, dam, and siblings for a period of 1 h per day over PN Days 2-9, while their siblings remained in the nest. In addition, randomly selected litters served as unhandled controls. On PN Day 26 all pups were weaned and chronically implanted for recording of evoked field potentials and induction of hippocampal long-term potentiation. At 30 days of age, pups from the three treatment groups (isolated, nonisolated siblings, and unhandled controls) were tested for their ability to establish and maintain long-term potentiation across the perforant path/hippocampal dentate granule cell synapse. Changes in population EPSP slope and population spike amplitude (PSA) recorded following tetanization were used to assess the effects of neonatal isolation on hippocampal response measures. No significant between-group differences were obtained for input/output response curves constructed prior to tetanization. All three groups showed immediate and significant enhancement of the PSA measure at 15 min posttetanization. The level of PSA enhancement obtained from previously isolated pups was significantly greater than that obtained from both the nonisolated sibling and unhandled control groups. PSA enhancement in both the nonisolated and unhandled animals decayed to baseline 48-72 h after tetanization, while isolates showed no significant decay of the PSA measure at this period. Neonatal isolation was found to significantly enhance both the magnitude and duration of dentate granule cell response to tetanizing stimulations applied during early adolescence, a full 3 weeks after termination of the isolation paradigm. The results suggest that regularly repeated isolation stress occurring during infancy has an enduring impact on dentate neuroplasticity.