Maturational sequence of newly generated neurons in the dentate gyrus of the young adult rhesus monkey

Abstract

The generation of new neurons in the hippocampal dentate gyrus of adult mammals has been characterized in rodents, but the details of this process have not been described in the primate. Eleven young adult rhesus monkeys were given an injection of the DNA synthesis phase marker bromodeoxyuridine (BrdU) and killed at varying survival intervals (2 hours to 98 days). The immature neuronal marker TUC-4 (TOAD/Ulip/CRMP-4) was used to define three stages of morphological maturation. Stage I neurons had small somata and lacked dendrites. Stage II neurons had larger somata and short dendrites. Stage III neurons were similar in size to mature granule cells and had branching dendrites that extended into the molecular layer. Examination of TUC-4-positive immature neurons colabeled with BrdU indicated that stage I neurons first appeared 2 days after BrdU injection, stage II neurons at 14 days, and stage III neurons at 35 days. Electron microscopy of TUC-4-labeled cells showed that stage I cells had ultrastructural features of immature neurons, whereas stage III neurons were similar to mature granule cells and formed synapses in the molecular layer. This suggests that stage III neurons could potentially integrate into the circuitry of the dentate gyrus. This study shows that the maturational sequence for new neurons in the adult monkey is similar to that of the adult rodent; however, maturation takes a minimum of 5 weeks in the monkey, which is substantially longer than what has been reported in rodents.

Selective lesion of the hippocampus increases the differentiation of immature neurons in the monkey amygdala

“…The decrease in average neuron soma size may also reflect the fact that newly maturing neurons did not establish the same complement of connections as the preexisting neurons, and thus remained smaller than neurons already present in the amygdala that normally establish long distance connections, as is observed in other brain regions (7). This hypothesis is consistent with the fact that the size of a developing neuron soma is related to the length of its projection and its level of connectivity (42).…”

A morphologically distinct granule cell type in the dentate gyrus of the red fox correlates with adult hippocampal neurogenesis

“…In other long-living species such as marmoset monkeys, proliferation occurs on a comparatively low level and also decreases with age (Leuner et al, 2007). However, marmosets might compensate for a low rate of cell division by an extended maturation of the adult born neurons, as has been shown for rhesus monkeys (Ngwenya et al, 2006).…”

“…Species-specific variations in the length of the maturation of newly born neurons have been reported before. For rodents, the time until a new born granule cells shows mature features is around 30 days (Brown et al, 2003;Kempermann et al, 2003), in contrast to possibly more than 3 months in monkeys (Ngwenya et al, 2006;Ngwenya et al, 2008). On the background of low proliferation, requirements for these highly excitable young neurons (Amrein et al, 2004b;Cameron and McKay, 2001;Deng et al, 2009) may be mediated by an extended maturation period.…”

Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats

“…Conversely, chronic treatment with different classes of ADs increases neurogenesis and reverses stress-induced inhibition of neurogenesis in adult hippocampus (Malberg et al, 2000;Czeh et al, 2001;Malberg and Duman, 2003;Alonso et al, 2004). Moreover, the time course of maturation of newly generated neurons in the dentate gyrus (DG) is generally consistent with the delayed onset of actions of ADs (Ngwenya et al, 2006). The most compelling evidence linking adult hippocampal neurogenesis with ADs comes from the elegant studies demonstrating that suppression of hippocampal neurogenesis by localized x-ray irradiation inhibits behavioral actions of different ADs in rodent behavioral screens for AD activity (Santarelli et al, 2003;Jiang et al, 2005;Airan et al, 2007).…”