Preadolescent exposure to a sexually mature, unrelated male rat reduces postadolescent social recognition memory and CA2 c-Fos labeling.

Introduction: Social memory involves social recognition: the ability to discriminate between two or more conspecifics when one has been previously encountered. The CA2 region of the hippocampus has been implicated in social memory, as lesions and dysfunction to this area lead to social memory impairments. A variety of psychogenic manipulations during postnatal sensitive developmental periods are associated with social memory impairments later in life. Methods: In this study, we exposed preadolescent rats to a sexually, mature unrelated male and examined whether this was associated with changes in postadolescent social memory and c-Fos labeling in the CA2 region. Male and female Long-Evans rats were exposed to a male, adult rat on postnatal days 19-21 (P19-21). Social memory was measured during the postadolescent period and defined as increased interactions towards a novel age-matched rat in contrast to a previously-encountered age-matched rat. After the test, rats were euthanized and brain tissue was then collected to quantify c-Fos labeling within the CA2 region. Results: Compared to home cage controls and controls not exposed to the adult male, male and female rats exposed to the unrelated adult during preadolescence were unable to discriminate between a novel and previously encountered conspecific during the postadolescent test showing social memory deficits. The groups that showed social recognition deficits also had significantly fewer c-Fos-positive cells within the CA2 region compared to the control groups. Discussion: These findings indicate that threatening psychogenic encounters during preadolescence can have detrimental long-term effects on social memory potentially via disrupted activity in the CA2 hippocampal region.

Spatial exploration induced expression of immediate early genes Fos and Zif268 in adult-born neurons Is reduced after pentylenetetrazole kindling.

Seizure activity stimulates adult neurogenesis, the birth of new neurons, in the hippocampus. Many new neurons that develop in the presence of repeatedly induced seizures acquire abnormal morphological and functional characteristics that can promote network hyperexcitability and hippocampal dysfunction. However, the impact of seizure induced neurogenesis on behaviour remains poorly understood. In this study, we investigated whether adult-born neurons generated immediately before and during chronic seizures were capable of integration into behaviorally relevant hippocampal networks. Adult rats underwent pentylenetetrazole (PTZ) kindling for either 1 or 2 weeks. Proliferating cells were labelled with BrdU immediately before kindling commenced. Twenty-four hours after receiving their last kindling treatment, rats were placed in a novel environment and allowed to freely explore for 30 min. The rats were euthanized 90 min later to examine for behaviourally-induced immediate early gene expression (c-fos, Zif268). Using this approach, we found that PTZ kindled rats did not differ from control rats in regards to exploratory behaviour, but there was a marked attenuation in behaviour-induced expression of Fos and Zif268 for rats that received 2 weeks of PTZ kindling. Further examination revealed that PTZ kindled rats showed reduced colocalization of Fos and Zif268 in 2.5 week old BrdU + cells. The proportion of immature granule cells (doublecortin-positive) expressing behaviorally induced Zif268 was also significantly lower for PTZ kindled rats than control rats. These results suggest that chronic seizures can potentially disrupt the ability of adult-born cells to functionally integrate into hippocampal circuits important for the processing of spatial information.

Chronic Jet Lag Simulation Decreases Hippocampal Neurogenesis and Enhances Depressive Behaviors and Cognitive Deficits in Adult Male Rats.

There is a long history that protracted periods of circadian disruption, such as through frequent transmeridian travel or rotating shift work, can have a significant impact on brain function and health. In addition, several studies have shown that chronic periods of circadian misalignment can be a significant risk factor for the development of depression and anxiety in some individuals with a history of psychiatric illness. In animal models, circadian disruption can be introduced through either phase advances or delays in the light-dark cycle. However, the impact of chronic phase shifts on affective behavior in rats has not been well-studied. In the present study, male rats were subjected to either weekly 6 h phase advances (e.g., traveling eastbound from New York to Paris) or 6 h phase delays (e.g., traveling westbound from New York to Hawaii) in their light/dark cycle for 8 weeks. The effect of chronic phase shifts was then examined on a range of emotional and cognitive behaviors. We found that rats exposed to frequent phase advances, which mirror conditions of chronic jet lag in humans, exhibited impairments in object recognition memory and showed signature symptoms of depression, including anhedonia, increased anxiety behavior, and higher levels of immobility in the forced swim test. In addition, rats housed on the phase advance schedule also had lower levels of hippocampal neurogenesis and immature neurons showed reduced dendritic complexity compared to controls. These behavioral and neurogenic changes were direction-specific and were not observed after frequent phase delays. Taken together, these findings support the view that circadian disruption through chronic jet lag exposure can suppress hippocampal neurogenesis, which can have a significant impact on memory and mood-related behaviors.