The storage and persistence of memories depends on plasticity in the hippocampus. Adult neurogenesis produces new neurons that mature through critical periods for plasticity and cellular survival, which determine their contributions to learning and memory. However, most granule neurons are generated prior to adulthood; the maturational timecourse of these neurons is poorly understood compared to adult-born neurons but is essential to identify how the dentate gyrus (DG), as a whole, contributes to behavior. To characterize neurons born in the early postnatal period, we labeled DG neurons born on postnatal day 6 (P6) with BrdU and quantified maturation and survival across early (1 hr to 8 weeks old) and late (2-6 months old) cell ages. We find that the dynamics of developmentally-born neuron survival is essentially the opposite of neurons born in adulthood: P6-born neurons did not go through a period of cell death during their immature stages (from 1 to 8 weeks). In contrast, 17% of P6-born neurons died after reaching maturity, between 2 and 6 months of age. Delayed death was evident from the loss of BrdU cells as well as pyknotic BrdU caspase3 neurons within the superficial granule cell layer. Patterns of DCX, NeuN, and activity-dependent Fos expression indicate that developmentally-born neurons mature over several weeks and a sharp peak in zif268 expression at 2 weeks suggests that developmentally-born neurons mature faster than adult-born neurons (which peak at 3 weeks). Collectively, our findings are relevant for understanding how developmentally-born DG neurons contribute to memory and disorders throughout the lifespan. High levels of early survival and zif268 expression may promote learning, while also rendering neurons sensitive to insults at defined stages. Late neuronal death in young adulthood may result in the loss of hundreds of thousands of DG neurons, which could impact memory persistence and contribute to hippocampal/DG atrophy in disorders such as depression.

The storage and persistence of memories depends on plasticity in the hippocampus. Adult neurogenesis produces new neurons that mature through critical periods for plasticity and cellular survival, which determine their contributions to learning and memory. However, most neurons are generated in early postnatal development; the maturational timecourse of these neurons is poorly understood compared to adult-born neurons, but is essential to identify how the dentate gyrus, as a whole, contributes to behavior. To characterize the survival and maturational timecourse of dentate gyrus neurons born in the early postnatal period, we labeled neurons born on postnatal day 6 (P6) with BrdU and quantified maturation and survival across early (1 hour to 8 weeks old) and late (2-6 months old) cell ages. We find that the dynamics of developmentallyborn neuron survival is essentially the opposite what has been published for neurons born in adulthood: P6-born neurons did not go through a period of cell death during their immature stages (from 1-8w). In contrast, 17% of P6-born neurons died after reaching maturity, between 2-6 months of age. Delayed death was evident from the loss of BrdU + cells as well as pyknotic caspase3 + neurons within the superficial granule cell layer. Patterns of DCX, NeuN and activity-dependent Fos expression indicate that developmentally-born neurons mature over several weeks and a sharp peak in zif268 expression at 2 weeks suggests that developmentally-born neurons mature faster than adult-born neurons (previously been shown to peak at 3 weeks). Collectively, our findings are relevant for understanding how developmentally-born dentate gyrus neurons contribute to memory and disorders throughout the lifespan. High levels of early survival and zif268 expression may promote learning, while also rendering neurons sensitive to insults at defined stages. Late neuronal death in young adulthood may result in the loss of hundreds of thousands of dentate gyrus neurons, which could impact memory persistence and contribute to hippocampal/dentate gyrus atrophy in disorders such as depression.

Objective The etiology of persistent memory complaints after concussion is poorly understood. Memory perfectionism (highly valuing memory ability and intolerance of minor memory lapses) may help explain why some people report persistent subjective memory problems in the absence of corresponding objective memory impairment. This study investigated the relationship between memory perfectionism and persistent memory complaints after concussion. Methods Secondary analysis of baseline data from a randomized controlled trial. Adults (N = 77; 61% women) with persistent symptoms following concussion were recruited from outpatient specialty clinics. Participants completed the National Institutes of Health Toolbox Cognition Battery, Test of Memory Malingering-Trial 1, and questionnaires measuring memory perfectionism (Metamemory in Adulthood-Achievement subscale), forgetfulness and other postconcussion symptoms (Rivermead Postconcussion Symptoms Questionnaire; RPQ), and depression (Patient Health Questionnaire-2) at M = 17.8 weeks postinjury. Patients with versus without severe memory complaints (based on the RPQ) were compared. Results Memory perfectionism was associated cross-sectionally with severe memory complaint, after controlling for objective memory ability, overall cognitive ability, and depression (95% confidence interval for odds ratio = 1.11–1.40). Sensitivity analyses showed that this relationship did not depend on use of specific objective memory tests nor on inclusion of participants who failed performance validity testing. In a control comparison to test the specificity of identified relationships, memory perfectionism was not associated with severe fatigue (95% confidence interval for odds ratio = 0.91–1.07). Conclusions Memory perfectionism may be a risk factor for persistent memory symptoms after concussion, with potential relevance to the spectrum of functional cognitive disorders more broadly.

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