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Functional heterogeneity of dentate gyrus mossy cells along the longitudinal axis of the hippocampus

ABSTRACT: Glutamatergic mossy cells (MCs) display unique connectivity by projecting their axons bilaterally along the longitudinal axis of the dentate gyrus (DG). However, it is unclear whether MCs are heterogeneous in their neuronal properties and functions. Here, we demonstrated within-cell-type heterogeneity of MC subpopulations depending on their dorsoventral location. Gene expression profiles of dMCs and vMCs were associated with different neurobiological processes including axon guidance, synaptic transmission, and neurometabolism. Despite common activation by external stimuli, dMCs, but not vMCs, provide net inhibitory control of granule cell excitability across the longitudinal axis of the DG. Intrinsic heterogeneity within MCs provides substantial mechanisms underlying functional differentiation as well as association across the longitudinal extent of the hippocampus.

ORGANISM(S): Mus musculus

PROVIDER: GSE156004 | GEO | 2026/07/22

REPOSITORIES: GEO

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Project description:The dentate gyrus (DG) of the hippocampus is one of major targets for antidepressant treatments. Our recent research has revealed that selective serotonin reuptake inhibitor (SSRI) treatment causes a long-lasting change in the phenotypes of mature dentate granule neurons to immature state in adult mouse DG. However, it is unknown whether this M-bM-^@M-^\dematurationM-bM-^@M-^] of DG is a common effect of antidepressant treatments and what mechanisms underlie it. Using electroconvulsive stimulation (ECS), a model of highly effective and fast-acting antidepressant therapy, here we show that neural stimulation via ECS induces rapid and lasting dematuration of granule neurons in DG. A single or few times of stimulation transiently reduced mature marker expression and mature synaptic functions. Repetitive stimulation converted this transient dematuration into a stable form lasting more than 1 month. Dematured granule neurons showed higher excitability, and an increase in GABA-mediated inhibition by the benzodiazepine diazepam prevented the lasting maintenance phase of dematuration without affecting the initial induction phase. Our study suggests that dematuration of DG is a common cellular mechanism underlying effects of different types of antidepressant treatments, and demonstrate a novel role for excitation/inhibition balance in bidirectional regulation of the state of neuronal maturation in the adult brain. Mice were decapitated after the 11 times of ECS (or Sham) or 4 weeks treatment of fluoxetine (or vehicle) at a dose of 22 mg/kg. The brains were sliced and the frequency facilitation of mossy fiber synapse was measured in each sample. The samples which exhibited low frequency facilitation were selected to be used as dematured DG (n = 3) and the dentate gyrus was dissected from each sample. Total RNA was extracted by using an RNeasy micro kit (Qiagen) and the samples of the same groups were put together. From each group, 100 ng of total RNA was amplified with 3M-bM-^@M-^YIVT Express kit (Affymetrix, Inc., Santa Clara, CA, USA). All samples were hybridized to the GeneChip mouse genome 430A 2.0 array (Affymetrix, Inc.), and the microarray suite 5.0 of the Affymetrix gene chip operating software was used for the analysis of the GeneChip data.

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Functional heterogeneity of dentate gyrus mossy cells along the longitudinal axis of the hippocampus

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