Age and sex-dependent differences in activity, plasticity and response to stress in the dentate gyrus

• Pre-pubertal and adult dentate gyrus shows differences in intrinsic excitability and local circuit activity.
• The effects of stress on dentate gyrus functioning are age-dependent and sex-dependent.
• Sex is an important parameter in the sensitivity to stress of the dentate gyrus local circuit.
• Interactive age/sex/stress effects on the dentate gyrus underlie its role in hippocampal function.

In the last decade, early-onset of affective illness has been recognized as a major public health problem. However, clinical studies indicate that although children experience the symptoms of anxiety and depression in much the same way as adults, they display and react to those symptoms differently (Bostic et al., 2005). Recently, we have demonstrated that similar differences in symptoms are found also between adult and juvenile rats (Jacobson-Pick and Richter-Levin, 2010). Especially the hippocampus is believed to be vulnerable to stress-related illness, as this brain region has a high density of corticoid receptors. The hippocampus is known to finalize its development, and particularly that of GABA-related functions, into adolescence (Bergmann et al., 1991, Harris et al., 1992, Nurse and Lacaille, 1999, Lopez-Tellez et al., 2004 and Jacobson-Pick et al., 2008) and may thus be differentially sensitive to environmental challenges in childhood and in adulthood. In this study we explored the differences in activity and plasticity of the dentate gyrus between pre-pubertal and adult rats in vivo. Furthermore, we have examined the impact of exposure to stress either during pre-puberty or in adulthood on dentate gyrus electrophysiology. In both male and female rats, marked differences were found for intrinsic excitability and local circuit activity between pre-pubertal and adult animals. Exposure to forced swim stress resulted in significant alterations of dentate gyrus activity and plasticity in male rats with differences between adult and pre-pubertal animals. Stress had far less impact on females’ dentate electrophysiology.The results are in agreement with the differences in behavioral response to stress between pre-pubertal and adult rats, and with reported differences for the sensitivity of male and female rats in performing hippocampus-dependent tasks under stress, such as the active avoidance task.