The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for?

Several theories have proposed possible functions of adult neurogenesis in learning processes on a systems level, such as the avoidance of catastrophic interference and the encoding of temporal and contextual information, and in emotional behavior. Under the assumption of such functionality of new neurons, the question arises: what are the consequences of adult hippocampal neurogenesis beyond the temporally immediate computational benefit? What might provide the evolutionary advantage of maintaining neurogenesis in the dentate gyrus but almost nowhere else? I propose that over the course of life, activity-dependently regulated adult neurogenesis reveals its true significance in the retained ability for lasting and cumulative network adaptations. The hippocampal precursor cells that generate new neurons with their particular acute function represent a ‘neurogenic reserve’: the potential to remain flexible and plastic in hippocampal learning when the individual is exposed to novelty and complexity.

Introduction

The ‘neurogenic reserve’ hypothesis, proposed here, intends to explain how neurogenesis in the adult hippocampus might contribute to the maintenance and promotion of hippocampal function in health and disease across the lifespan. The theory makes explicit reference to the neural reserve theory, first proposed by R. Katzman and P. Satz and elaborated, for example, by Y. Stern 1, 2, 3, 4. A ‘neural reserve’ is sought as explanation, for example, for the observation that in cases of neurodegenerative disease, the amount of neuropathological damage shows no tight correlation with the functional impairment [5]. Apparently healthy subjects might die with a brain full of Alzheimer-like plaques, although modest plaque load in other individuals might already be associated with massive dementia [6]. The neural reserve would represent the brain's compensatory potential in the face of neurodegeneration. This reserve is thought to lie in ‘brain networks or cognitive paradigms that are less susceptible to disruption, perhaps [because] they are more efficient or have greater capacity’ [7]. The neurogenic reserve theory specifies that in the hippocampus, adult neurogenesis might activity- and experience-dependently produce a potential for sustained cellular plasticity with increasing age but from childhood onward, thereby providing such greater capacity and efficiency. The particular relevance of this special case of a reserve derives from the prominent role of the hippocampus in higher cognition, most notably learning and memory and emotional behavior. In animal experiments, both physical and cognitive ‘activity’ reduced the age-dependent decline in precursor cell proliferation in the dentate gyrus 8, 9, 10. Sustained exposure to a complex environment, even if started only in midlife, maintained neurogenesis at a higher level and also resulted in improved learning performance [9]. Thereby, adult neurogenesis might contribute to the well-known but poorly understood observation that activity – in the sense of leading an active life – is ‘good for the brain’ and promotes successful aging.