Major unsolved points in adult neurogenesis: doors open on a translational future?

The ultimate goal of exploiting adult neurogenesis (AN) as a source of cell replacement is far from being achieved. In spite of many data gathered during the last two decades on homeostatic and reactive neurogenesis, it is evident that such knowledge is not sufficient for granting translational outcomes. By asking the question whether AN research field has to be considered as a dead end in such a perspective, here we review some major unresolved issues: multifaceted evolutionary constraints emerged in mammals, stem/progenitor cell type/availability and tissue permissivity, the possible impact on other brain functions and/or interplay with other forms of plasticity, and relevance in humans. We suggest that full understanding of AN biological processes is an essential step to their possible exploitation for brain repair, and that further fundamental, multidisciplinary research is required before translational outcomes can be reached. Scientist's attitude and their communication skills are also important. To avoid overestimation of AN reparative potential, more distant goals of cell replacement should be kept clearly distinct from restorative approaches involving AN plasticity, both representing translational perspectives

How neurogenesis finds its place in a hardwired sensory system

So far most studies on adult neurogenesis aimed to unravel mechanisms and molecules regulating the integration of newly generated neurons in the mature brain parenchyma. The exceedingly abundant amount of results that followed, rather than being beneficial in the perspective of brain repair, provided a clear evidence that adult neurogenesis constitutes a necessary feature to the correct functioning of the hosting brain regions. In particular, the rodent olfactory system represents a privileged model to study how neuronal plasticity and neurogenesis interact with sensory functions. Until recently, the vomeronasal system (VNS) has been commonly described as being specialized in the detection of innate chemosignals. Accordingly, its circuitry has been considered necessarily stable, if not hard-wired, in order to allow stereotyped behavioral responses. However, both first and second order projections of the rodent VNS continuously change their synaptic connectivity due to ongoing postnatal and adult neurogenesis. How the functional integrity of a neuronal circuit is maintained while newborn neurons are continuously added—or lost—is a fundamental question for both basic and applied neuroscience. The VNS is proposed as an alternative model to answer such question. Hereby the underlying motivations will be reviewed

The Interplay between Reproductive Social Stimuli and Adult Olfactory Bulb Neurogenesis

Adult neurogenesis is a striking form of structural plasticity that adapts the brain to the changing world. Accordingly, new neuron production is involved in cognitive functions, such as memory, learning, and pattern separation. Recent data in rodents indicate a close link between adult neurogenesis and reproductive social behavior. This provides a key to unravel the functional meaning of adult neurogenesis in biological relevant contexts and, in parallel, opens new perspectives to explore the way the brain is processing social stimuli. In this paper we will summarize some of the major achievements on cues and mechanisms modulating adult neurogenesis during social behaviors related to reproduction and possible role/s played by olfactory newborn neurons in this context. We will point out that newborn interneurons in the accessory olfactory bulb (AOB) represent a privileged cellular target for social stimuli that elicit reproductive behaviors and that such cues modulate adult neurogenesis at two different levels increasing both proliferation of neuronal progenitors in the germinative regions and integration of newborn neurons into functional circuits. This dual mechanism provides fresh neurons that can be involved in critical activities for the individual fitness, that is, the processing of social stimuli driving the parental behavior and partner recognition