3D neuronal mitochondrial morphology in axons, dendrites, and somata of the aging mouse hippocampus.

Julie Faitg,Amy E Vincent,Clay Lacefield,Stylianos Kosmidis,Tracey Davey,Kathryn White,Amy K Reeve,Eric R Kandel,Ross Laws,Martin Picard

doi:10.1016/j.celrep.2021.109509

Abstract

SUMMARYThe brain’s ability to process complex information relies on the constant supply of energy through aerobic respiration by mitochondria. Neurons contain three anatomically distinct compartments—the soma, dendrites, and projecting axons—which have different energetic and biochemical requirements, as well as different mitochondrial morphologies in cultured systems. In this study, we apply quantitative three-dimensional electron microscopy to map mitochondrial network morphology and complexity in the mouse brain. We examine somatic, dendritic, and axonal mitochondria in the dentate gyrus and cornu ammonis 1 (CA1) of the mouse hippocampus, two subregions with distinct principal cell types and functions. We also establish compartment-specific differences in mitochondrial morphology across these cell types between young and old mice, highlighting differences in age-related morphological recalibrations. Overall, these data define the nature of the neuronal mitochondrial network in the mouse hippocampus, providing a foundation to examine the role of mitochondrial morpho-function in the aging brain.

Highlights

The mammalian hippocampus is a specialized brain structure underlying the cerebral neocortex with a role in encoding episodic memories and spatial maps, crucial features for organizing adaptive behavior (Hartley et al, 2013)
Compartment-specific imaging of neuronal mitochondria in cornu ammonis 1 (CA1) and dentate gyrus (DG) regions Young (4 months, n = 3) and old (18 months, n = 4) C57BL/6J mice were transcardially perfused with fixative after brief anesthesia to preserve in vivo mitochondrial morphology
The dendrites from the middle of the molecular layer belong to the same cell type as the somata; in contrast, the axons identified in the DG most likely arise and project from the medial entorhinal cortex, whereas CA1 axons likely arise from the CA3, rather than from the principal cell type in the regions themselves

Summary

Introduction

The mammalian hippocampus is a specialized brain structure underlying the cerebral neocortex with a role in encoding episodic memories and spatial maps, crucial features for organizing adaptive behavior (Hartley et al, 2013). Prior to the establishment of terminally differentiated neural structures, the function and positioning of mitochondria determine axonal and dendritic development (Courchet et al, 2013) and can influence axonal regeneration (Kann and Kovacs, 2007; Schon and Przedborski, 2011), illustrating the broad range of effects mitochondria have on neuronal behavior (Lee et al, 2018). Given these diverse roles, it is likely that mitochondria differ between principal cell types in DG and CA1, and they may underlie the relative susceptibility of these areas to age-related changes

Methods

Results

Conclusion