Age-related naturally occurring depression of hippocampal neurogenesis does not affect trace fear conditioning.

New neuron production throughout adulthood in granule cell layer (GCL) of rat hippocampus is a well-known phenomenon. A role of new neurons in hippocampal learning has been proposed, but the question is still open. A reduction of neural precursor proliferation in GCL of 2-month-old rats to about 20%, induced by the cytostatic agent methylazoxymethanol, was found to cause impairment in trace conditioning, suggesting a role of immature neurons in this kind of hippocampus-dependent learning (Shors et al., Hippocampus 2002;12:578-584). Neurogenesis decreases with increasing age. In this study, neural precursor proliferation and newborn cell survival were evaluated in GCL of adult rats within a range of ages following development and preceding old age. In 5-month-old rats, neural precursor proliferation was reduced to 57% and newborn cell survival was reduced to 40% in comparison to rats of 2 months of age; in 12-month-old rats, the decrease was to 5 and 4%, respectively. Consistently, the density of immature neurons decreased to 41 and 13% in 5- and 12-month-old rats, respectively. The role of neurogenesis in trace fear conditioning was studied in this natural model of neurogenesis depression. No impairment in trace fear conditioning was found both in 5- and 12-month-old rats in comparison to 2-month-old rats, notwithstanding the decrease of neurogenesis that is marked in 12-month-old rats. This finding shows that a lower rate of neurogenesis is sufficient for learning in 12-month-old rats in comparison to young rats.

Learning may reduce neurogenesis in adult rat dentate gyrus.

Neuron production carries on throughout adult life in granule cell layer of mammalian dentate gyrus. The acquisition of a hippocampus-dependent task enhances newborn cell survival in granule cell layer (GCL) during the period in which several newborn cells die. In this paper the effect of learning, occurring after the maximal period of newborn cell death, on newborn cells was investigated. Rats were trained for hippocampus-dependent learning in Morris water maze. 5-bromo-2'-deoxyuridine was administered 8-10 days before training beginning and labeled cells were counted after training. Learning decreased BrdU-labeled cell density in GCL, and increased TUNEL-positive cells. Moreover, learning diminished immature neuron density prevalently in the internal blade of GCL. Therefore, a different effect of learning on immature neuron survival, depending on the time elapsing from mitosis to learning, is suggested.

Persistently high corticosterone levels but not normal circadian fluctuations of the hormone affect cell proliferation in the adult rat dentate gyrus.

The dentate gyrus is one of the few brain structures where new neurons are added throughout adulthood in several mammalian species, including humans. Production of new neurons can be regulated by factors which influence cell proliferation or newborn cell survival. Supplementation or deprivation of glucocorticoids, adrenal hormones involved in the response to stress, affect cell proliferation, leading to a decrease or an increase, respectively, in the number of newborn cells. Glucocorticoid secretion under physiological conditions follows a circadian pattern. We thus investigated a possible relationship between cell proliferation and circadian oscillations of corticosterone secretion in the adult rat dentate gyrus. Corticosterone is the species-specific glucocorticoid hormone of the rat. 5-Bromo-2'-deoxyuridine was used to evaluate cell proliferation at 4 different time points in the light-dark cycle. No correlation was found between corticosterone circadian oscillations and cell proliferation in the adult dentate gyrus. In contrast, constantly high corticosterone levels, obtained by implanting corticosterone pellets, decreased cell proliferation in particular zones of the dentate gyrus, i.e. the hilus and the superior blade of the granule cell layer. These findings show that a short, physiologically occurring exposure to high corticosterone levels does not influence cell proliferation, whereas a lengthy exposure to this hormone does induce anatomically localized proliferative changes.