Abstract
Chronic early life stress increases adult risk for depression, bipolar disorder and schizophrenia, illnesses characterized by aberrant functions of cognition and memory. We asked whether chronic early life stress disrupts maturation of gamma oscillations, on which these functions depend. Lifelong impairment of the stress response results from separation of rat pups from the dam for three hours per day during a critical period of hippocampal development (PNDs 2–14). Parvalbumin-expressing interneurons, including the basket cell network which is fundamental to gamma oscillations, are reduced in number in post mortem studies of bipolar disorder and schizophrenia, and in chronically-stressed adult rats. To determine effects of chronic early life stress on gamma oscillations, we separated pups from dams once each day on PNDs 2–14 and recorded in vitro at PNDs 15–21. In control pups, separated for 15 minutes per day, gamma power had highly significant correlations with both age (p = 0.0022) and weight (p = 0.0024); gamma in pups separated for 180 minutes per day was not correlated with either factor. ANCOVA indicated significant differences between the groups in both measures. These findings indicate that chronic early life stress can disrupt maturation of the gamma oscillation network.
Highlights
Severe stress, such as that produced by a single 24-hour separation from the dam, can “break through” the SHRP to cause a significant rise in plasma corticosteroids
The progressive maturation of hippocampal gamma oscillations, approximately spanning postnatal days 12 to 25 in rat pups, which occurs in parallel with and as a function of the morphological and electrophysiologcal maturation of PVBCs18, has not to our knowledge been documented with data points taken at time frames appropriate to the rapid changes occurring during this period, either in vivo or in vitro
Analysis of covariance (ANCOVA) showed that the relationships between age and gamma power were significantly different in HMS15 versus HMS180 pups (p = 0.0342)
Summary
Severe stress, such as that produced by a single 24-hour separation from the dam, can “break through” the SHRP to cause a significant rise in plasma corticosteroids. The practice of pooling of data from animals which are still morphologically and electrophysiologically immature assumes that there are no significant age-related differences between 14- and 22-day old pups or between those pups and adults which would need to be considered in interpreting experimental results. This assumption is in conflict with what we know about the electrophysiological maturation of cellular networks in hippocampus
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