Adult Neurogenesis in Mammals: Variations and Confusions

Abstract

Mammalian adult neurogenesis has remained enigmatic. Two lines of research have emerged. One focuses on a potential repair mechanism in the human brain. The other aims at elucidating its functional role in the hippocampal formation, chiefly in cognitive processes; however, thus far it has been unsuccessful. Here, we try to recognize the sources of errors and conceptual confusion in comparative studies and neurobehavioral approaches with a focus on mice. Evolutionarily, mammalian adult neurogenesis appears as protracted juvenile neurogenesis originating from precursor cells in the secondary proliferation zones, from where newly formed cells migrate to target regions in the forebrain. This late developmental process is downregulated differentially in various brain structures depending on species and age. Adult neurogenesis declines substantially during early adulthood and persists at low levels into senescence. Short-lasting episodes in proliferation or reduction of adult neurogenesis may reflect a multitude of factors, and have been studied chiefly in mice and rats. Comparative studies face both species-specific variations in staining and technical abilities of laboratories, lacking quantification of important reference measures (e.g. granule cell number) and evaluation of maturational markers whose persistence might be functionally more relevant than proliferation rates. Likewise, the confusion about the functional role of variations in adult hippocampal neurogenesis has many causes. Prominent is an inferential statistical approach, usually with low statistical power. Interpretation is complicated by multiple theories about hippocampal function, often unrealistically extrapolating from humans to rodents. We believe that the field of mammalian adult neurogenesis needs more critical thinking, more sophisticated hypotheses, better statistical, technical and behavioral approaches, and a broader conceptual perspective incorporating comparative aspects rather than neglecting them.

Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

“…Neuronal proliferation in postembryonic mammals is primarily restricted to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricles and third ventricle [reviewed by Doetsch andScharff, 2001 andLipp andBonfanti, 2016]. Neural precursors then migrate less than ∼ 100 μm into the granular layer of the dentate gyrus where they become mature granule cells [Amaral et al, 2007], or several millimeters along the rostral migratory stream into the olfactory bulb, respectively, and become primarily granule neurons, and to a lesser extent, periglomerular, and short-axon neurons [Whitman and Greer, 2007;Lepousez et al, 2013].…”

“…Future work should seek to add tools allowing direct manipulations of new neurons to study neurogenesis in cross-specific studies as well. For more details and important critiques of work done in mammals, see Lipp and Bonfanti [2016 ].…”

Evolutionary Shaping of Adult Hippocampal Neurogenesis in Mammals–Cognitive Gain or Developmental Priming of Personality Traits?

“…For example, doublecortin (DCX) is a reasonable proxy for estimating proliferation rates in mice and rats. In other species such markers persist for long periods after the cessation of proliferation or appear even generated de novo (Amrein, 2015; Penz et al, 2015; Lipp and Bonfanti, 2016). Therefore, AHN and its potential relation to natural selection will refer here to simple proliferation only.…”

Preface

“…In rats, primates, and humans, adult neurogenesis is found in the subgranular zone of the dentate gyrus, and in the subventricular zone of the lateral ventricle, producing neurons that migrate to the olfactory bulb. In other mammals, the presence of new cells is more variable [Brus et al, 2013;Lipp and Bonfanti, 2016]. Adult neurogenesis is also seen in invertebrates [Beltz et al, 2016].…”

“…I summarize what is known about the role of adult neurogenesis and behavioral plasticity in amphibians and reptiles [Powers, 2016]. Finally, Lipp and Bonfanti [2016] discuss studies of adult neurogenesis in mammals. I thank all the contributors for their work and their excellent contributions to this volume.…”