Mature Neurons In Dentate Gyrus Research Articles

Stressful experiences differentially regulate immediate-early genes and stress hormone receptors in immature and mature dentate gyrus neurons

Stressful experiences differentially regulate immediate-early genes and stress hormone receptors in immature and mature dentate gyrus neurons

Maternal immune activation differentially impacts mature and adult-born hippocampal neurons in male mice.

Schizophrenia is associated with deficits in the hippocampus, a brain area important for learning and memory. The dentate gyrus (DG) of the hippocampus develops both before and after birth. To study the relative contribution of mature and adult-born DG granule cells to disease etiology, we compared both cell populations in a mouse model of psychiatric illness resulting from maternal immune activation. Polyriboinosinic-polyribocytidilic acid (PolyIC, 5mg/kg) or saline was given on gestation day 15 to pregnant female C57Bl/6 mice. Male offspring (n=105), was administered systemic bromodeoxyuridine (BrdU, 50mg/kg) (n=52) or intracerebral retroviral injection into the DG (n=53), to label dividing cells at one month of age. Two months later behavioral tests were performed to evaluate disease phenotype. Immunohistochemistry and whole-cell patch clamping were used to assess morphological and physiological characteristics of DG cells. Three-month-old PolyIC exposed male offspring exhibited deficient pre-pulse inhibition, spatial maze performance and motor coordination, as well as increased depression-like behavior. Histological analysis showed reduced DG volume and parvalbumin positive interneuron number. Both mature and new hippocampal neurons showed modifications in intrinsic properties such as increased input resistance and lower current threshold, and decreased action potential number. Reduced GABAergic inhibitory transmission was observed only in mature DG neurons. Differential impairments in mature DG cells and adult-born new neurons may have implications for behavioral deficits associated with maternal immune activation.

Chronic inhibition of brain phospholipase A2 in adult rats impairs the survival of newborn mature neurons in the hippocampus.

Adult neurogenesis occurs in the hippocampal dentate gyrus (DG) and lateral ventricles, and includes cell proliferation and neuronal differentiation, maturation and survival. In vitro studies suggest a role for phospholipase A2 (PLA2) in neuronal differentiation/maturation and survival. This study aimed to investigate the effect of in vivo chronic inhibition of brain PLA2 in adult rats on the number of newborn mature neurons in the DG. Male Wistar rats were injected with BrdU (cell proliferation marker) and 2weeks later (beginning of neuronal maturation) sham-operated or infused intracerebroventricularly with either vehicle (DMSO in saline) or PLA2 inhibitor (MAFP dissolved in the vehicle) for 14days via osmotic minipump. The animals were euthanised 28days post-BrdU and their brains immunostained for BrdU and BrdU plus NeuN (mature neuronal marker) for analysis of surviving cells. MAFP reduced the number of BrdU(+) cells in the ventral DG (p<0.05 vs. sham; p<0.01 vs. DMSO) and the number of BrdU(+)NeuN(+) cells in the ventral (p<0.01 vs. sham and DMSO) and whole DG (p<0.02 vs. sham and DMSO). There was no effect of MAFP in the dorsal DG. These findings show that chronic PLA2 inhibition in adult rat hippocampus decreases the number of newborn mature neurons in the ventral DG (reflecting in the whole DG), perhaps by impairing neuronal maturation and survival, and suggest that PLA2 inhibition reported in the hippocampus of Alzheimer disease subjects might partly contribute to the neurogenic abnormalities found in the DG in this disease.

Changes in the Histone Acetylation Patterns during the Development of the Nervous System

Epigenetic modification such as DNA methylation and histone acetylation plays essential roles in many aspects of cellular function and development of animals. There is an increasing amounts of evidence for dynamic changes in the histone acetylation of specific gene segments, but little attempt was made to examine global pattern changes in the histone acetylation in developing nervous system. In this study, we found that acetylated histone H3 and H4 immunoreactivities were relatively weak in neuroepithelial cells in the ventricular zone of developing rat cerebral cortex or chick spinal cord, compared to the immature young neurons in the cortical plate of a rat embryo or lateral motor column in chick spinal cord. On the other hand, adult neural stem cells in the dentate gyrus (DG) of rat hippocampal formation did not exhibit such diminished histone acetylation, compared to neuroblasts and mature DG neurons. These results suggest that the level of histone acetylation is highly dynamic and tightly linked to the neuronal types and the differentiation stages.

Multiple Forms of Activity-Dependent Competition Refine Hippocampal Circuits In Vivo

Efficient memory formation relies on the establishment of functional hippocampal circuits. It has been proposed that synaptic connections are refined by neural activity to form functional brain circuitry. However, it is not known whether and how hippocampal connections are refined by neural activity in vivo. Using a mouse genetic system in which restricted populations of neurons in the hippocampal circuit are inactivated, we show that inactive axons are eliminated after they develop through a competition with active axons. Remarkably, in the dentate gyrus, which undergoes neurogenesis throughout life, axon refinement is achieved by a competition between mature and young neurons. These results demonstrate that activity-dependent competition plays multiple roles in the establishment of functional memory circuits in vivo.