What Is the Relationship Between Hippocampal Neurogenesis Across Different Stages of the Lifespan?

Abstract

Hippocampal neurogenesis has typically been studied during embryonic development or in adulthood, promoting the perception of two distinct phenomena. We propose a perspective that hippocampal neurogenesis in the mammalian brain is one continuous, lifelong developmental process. We summarize the common features of hippocampal neurogenesis that are maintained across the lifespan, as well as dynamic age-dependent properties. We highlight that while the progression of hippocampal neurogenesis across the lifespan is conserved between mammalian species, the timing of this progression is species-dependent. Finally, we discuss some current challenges in the hippocampus neurogenesis field, and future research directions to address them, such as time course analysis across the lifespan, mechanisms regulating neurogenesis progression, and interspecies comparisons. We hope that this new perspective of hippocampal neurogenesis will prompt fresh insight into previous research and inspire new directions to advance the field to identify biologically significant ways to harness the endogenous capacity for neurogenesis in the hippocampus.

Keywords: adult neurogenesis; embryonic neurogenesis; lifespan; neural stem cells; species differences.

FIGURE 1

Features of hippocampal neurogenesis across the lifespan. (A) Newborn neurons in the dentate gyrus of the hippocampus are generated through a common process across the lifespan. Neural stem cells divide to give rise to rapidly dividing intermediate progenitor cells. Intermediate progenitors give rise to neuroblasts, which have a limited capacity to divide before terminally differentiating and transitioning into immature neurons. Immature neurons have a distinct physiology which allows them to play a unique role in the hippocampal circuitry. This distinct physiology is lost as immature neurons undergo further synaptic development and reach the mature neuron stage. (B) The developmental progression of continuous dentate gyrus neurogenesis across the lifespan of a mouse. A robust and acute peak in neurogenesis occurs very early in the lifespan, around birth. Peak neurogenesis is followed by a dramatic exponential decline in neurogenesis which leads into the beginning of a protracted period of low-level neurogenesis that spans most of the lifespan. Neurogenesis levels continue to exponentially decline with age, albeit at a slower rate, during the protracted period of low-level neurogenesis. (C) Summary of continuous features and age-dependent properties of hippocampal neurogenesis across the lifespan in mice. While features such as neural stem cell lineage, cell fate, and neuronal maturation progression remain c across the lifespan, other features, such as neural stem cell properties, the function of neurogenesis, and neuronal maturation time, change in an age-dependent manner. (D) The developmental progression of dentate gyrus neurogenesis across the lifespan is conserved across species. However, the timing of peak neurogenesis and the start of the protracted period of low-level neurogenesis are shifted in a species-dependent manner.