Adult Neurogenesis in the Hippocampus

Health, Psychopathology, and Brain Disease

Juan J. Canales

• Publisher: Academic Press
• Year: 2016
• Print ISBN: 9780128019771
• eBook ISBN: 9780128019924
• Topic: Biological Sciences
• Subtopic: Neuroscience
• Index: Biological Sciences

Neurogenesis in the adult brain has emerged as one of the most dynamic and rapidly moving fields in modern neuroscience research. The implications of adult neurogenesis for health and well-being are wide-ranging, with findings in this area having distinct relevance for treatment and rehabilitation in neurology and psychopathology. Adult Neurogenesis in the Hippocampus addresses these implications by providing an up-to-date account on how neurogenesis in the adult hippocampus contributes to critical psychological and physiological processes, such as learning and memory, and how it is modified by life experiences, such as aging, environmental enrichment, exercise, and dieting. The book also provides the most current reviews of how adult hippocampal neurogenesis influences the pathogenesis of mood disorders, addiction, and key neurological disorders. This book is the ideal resource for researchers and advanced graduates seeking focused knowledge on the role of adult neurogenesis in brain health and disease. - Provides a unique overview of how adult hippocampal neurogenesis contributes to adaptive processes, brain psychopathology, and disease - Includes state-of-the-art reviews by leading world experts in adult neurogenesis

II

Neurogenesis in Health and Well-Being

Outline

Chapter 4. Learning and Memory

Chapter 5. Physical Exercise

Chapter 6. Dietary and Nutritional Regulation

Chapter 7. Aging

Chapter 4

Learning and Memory

C.M. Merkley, and J.M. Wojtowicz University of Toronto, Toronto, ON, Canada

Abstract

In this chapter, we will discuss the role of adult neurogenesis in learning and memory processes across the life span. The long-term survival and functionality of adult-born neurons are susceptible to environmental influences throughout life, particularly during specific critical periods of neuronal development, and may become selectively tuned or tagged with certain experiences. This may, in turn, influence their recruitment to cognitive processes later on. Although the molecular mechanisms underlying this phenomenon are elusive, it may be relevant to the idea that early-life experience can shape later-life cognitive function. A number of studies showing that alterations in neurogenesis are present before the onset of cognitive impairments and disease pathology in Alzheimer's disease mouse models support the hypothesis that changes in neurogenesis underlie cognitive impairments and that intervention targeting normal maintenance of neurogenesis may set the stage for healthy aging.

Keywords

Adult neurogenesis; Cognitive reserve; Critical periods; Dentate gyrus; Hippocampus; Learning; Memory; Neurogenic reserve; Plasticity

Introduction

In this chapter, we will address the role of adult neurogenesis (ANG) across the life span in learning and memory processes. We will outline behavioral, anatomical, and cellular studies that have shaped our understanding of the role of ANG in learning and memory. We will also discuss neurogenesis in the context of cognitive reserve in humans and recent findings using Alzheimer’s disease (AD) model mice that are changing the way we think about neurogenesis across the life span and the importance of its regulation as an early tool to promote healthy aging.

Our understanding of the role of ANG in learning and memory begins with two fundamental properties of newly born neurons: hyperplasticity and turnover. Hyperplasticity exists in several forms and during several distinct time windows or, so-called, critical periods. Turnover, refers to the transition of each successive cohort of new neurons from one developmental state to the next. For a few months following each cell’s birth these different states are represented by a distinct form of hyperplasticity such as altered excitation/inhibition balance, enhanced long-term potentiation, and enhanced ability to form dendritic spines. Each such state can occur transiently among neurons of certain ages but surrounded by neurons that are either younger or more mature. Thus, the hyperplastic neurons stand out from the rest of the surrounding neurons and may be preferentially used to alter the neuronal circuitry. However, as the neurons mature they assume a state of traditional plasticity, characteristic of the prenatally born neurons. This form of plasticity is still powerful but does not offer the sharp contrasts between neuronal populations afforded by the former.

Thus, ANG is a “living proof” of postnatal brain development and it is never at steady state. This may account for many apparently contradictory results from experiments that, in the past, may not have taken these different states into consideration. With improving understanding of the properties of ANG at the circuit level (Jonas & Lisman, 2014; Wojtowicz, 2012) there will come better understanding of the behavioral effects on learning and memory.

Adult Neurogenesis Across Life Span

The original description of a critical period in ANG came with a pioneering paper by Gould et al. (1999) who showed that a training task introduced during the second week of cellular life span can enhance the survival of a neuronal cohort in the dentate gyrus (DG). Although several reports supported these initial findings (Tashiro, Makino, & Gage, 2007; Trouche, Bontempi, Roullet, & Rampon, 2009), others did not or at least not entirely (Döbrössy et al., 2003; Snyder, Hong, Mcdonald, & Wojtowicz, 2005). For example, Snyder et al. (2005) did not observe enhanced survival effects, whereas Döbrössy et al. (2003) reported either enhanced or reduced survival of adult-born neurons that was dependent on the phase of the training that coincided with the birth of neurons. Other studies elaborated on this concept by showing that the enhanced survival of new neurons is correlated with subsequent improvement of spatial recognition (Tashiro et al., 2007) or spatial learning (Trouche et al., 2009). In particular, the outstanding feature of these survival effects was their specificity; i.e., in both studies the activity of the additional surviving neurons correlated with enhanced performance only on the tasks that were originally presented during the critical period.

Among the several regulatory mechanisms operating during this first developmental period, the neurotransmitter GABA stands out as particularly important, and serves as a dominant neurotransmitter in the DG. In general, GABA is inhibitory to the majority of mature granule neurons and its release is either regulated by phasic synaptic transmission via terminals of inhibitory interneurons (Overstreet Wadiche, Bromberg, Bensen, & Westbrook, 2005; Song et al., 2012, 2013) or tonically released into the extracellular space (Ge et al., 2006; Song et al., 2012). In addition, GABA serves as a regulatory trophic factor acting on the growing new neurons within the neurogenic zone of the DG. This action has been characterized in some detail and it differs depending on the developmental stage of target cells (Dieni, Chancey, & Overstreet-Wadiche, 2013).

The second critical period for ANG corresponds to 3–4 weeks after cellular birth and coincides with enhanced LTP in the afferent glutamatergic synapses contacting the new neurons. This enhancement is putatively caused by expression of an NR2B subtype of glutamate receptors present at the synapses (Ge, Yang, Hsu, Ming, & Song, 2007; Snyder, Kee, & Wojtowicz, 2001). This enhanced plasticity is not due to stronger synaptic input onto the adult-born/young neurons, but rather relates to the spiking properties of the young neurons (Mongiat, Esposito, Lombardi, & Schinder, 2009) and a low activation threshold (Marin-Burgin, Mongiat, Pardi, & Schinder, 2012). As such, this glutamate-dependent critical period follows the earlier one, in which GABA depolarization is a feature (see above), and hence it affects neurons that are more developed in terms of their synaptic connectivity. It is not clear whether this second critical period is separate from the first and whether it can support behavioral plasticity that is different from the GABA-mediated enhancement of neuronal survival. In fact, the GABA- and glutamate-dependent critical periods may overlap and there is ev...

Table of contents

• Cover image
• Title page
• Table of Contents
• Dedication
• Copyright
• List of Contributors
• Preface
• I. Neurobiology and Physiology of Hippocampal Neurogenesis
• II. Neurogenesis in Health and Well-Being
• III. Neurogenesis in Psychopathology and Disease
• Index