Ongoing interplay between the neural network and neurogenesis in the adult hippocampus

https://doi.org/10.1016/j.conb.2009.12.008Get rights and content

As a unique form of structural plasticity in the central nervous system, adult neurogenesis in the hippocampus alters network functions by continuously adding new neurons to the mature network, while at the same time is subjected to regulation by surrounding network activity. Here, we review the recently identified mechanisms through which network activity exerts its impacts on multiple steps of adult neurogenesis in rodents and culminates in the selective recruitment of new neurons. We also review recent progress on the study of cellular connectivity modified by new neurons in the dentate gyrus and its physiological functions in rodents. We believe that understanding these processes will allow eventual elucidation of the mechanisms controlling the development of balanced inputs and outputs for the adult-born neurons and reveal important insights into the cellular organization of learning and memory.

Introduction

It is well established that the dentate gyrus in the hippocampal formation is one of the two main structures in the brain with persistent neurogenesis in mammals [1]. In contrast to the other neural activity-dependent plasticity with structural modification within individual cells, adult neurogenesis represents a novel form of structural plasticity in the central nervous system by continuously adding new neurons to a mature network during adulthood. Among the plethora of intrinsic and extrinsic stimuli that modulate adult hippocampal neurogenesis [1], neural network activity has emerged as a prominent regulator in constantly sculpting the existing network through selective recruitment of new neurons, which in return serve to further refine network functions over time. Owing to the well-recognized functions of hippocampus in learning, memory, and emotion, and the strategically significant position of the dentate gyrus as the first station in the classic tri-synaptic structure of the hippocampus, the interplay between the neural network and neurogenesis in the adult hippocampus has been the subject of intensive study in the past decade. In this review, we aim to identify the emerging themes in this topic, including how network activity affects ongoing neurogenesis and how the integration of adult-born granule cells reshapes network functions. We want to emphasize that the literature we review here primarily comes from rodent studies and caution should be taken when extrapolating to other systems.

Section snippets

Impact of network activities on adult hippocampal neurogenesis

Ongoing neurogenesis in the dentate gyrus involves neural progenitor proliferation, neural production/differentiation/maturation, and final integration into the surrounding network. How does the activity of the existing network affect neurogenesis in the adult hippocampus (Figure 1)? The proposed excitation-neurogenesis coupling in the adult neural progenitors [2] can be generally achieved at multiple levels by either neurotransmitters or growth/trophic factors secreted from the neighboring

Impact of hippocampal neurogenesis on the existing network: from cellular perspectives to physiological functions

Analysis with electron microscopy (EM) in combination with retroviral GFP labeling suggests that adult-born neurons in the dentate gyrus compete with existing GCs not only for their excitatory and inhibitory inputs [39] but also for the targets of their mossy fibers, including CA3 neurons, INs and hilar mossy cells [40••, 41••], making cellular connections very similar to mature GCs (Figure 3a). Emerging from these studies, three modes of connectivity made by the adult-born neurons have been

Conclusions

In recent years significant progress has been made in understanding the molecular and cellular mechanisms for the exquisitely concerted interactions between the hippocampal network and ongoing neurogenesis in the dentate gyrus. However, largely for reasons of technical limitation, a majority of these previous studies have treated dentate neurogenesis as a unitary entity proceeding in a homogenous structure. Owing to the heterogeneous nature of the neuroanatomical connections of the dentate

Acknowledgements

Drs Li and Pleasure were funded by NIMH, NIDA and CIRM.

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