Gilles Gheusi

A niche for adult neurogenesis in social behavior

The structural and functional changes occurring into the brain is the hallmark of its tremendous capacity for dealing with the complexity that we are facing throughout life. It is also the hallmark of what neuroscientists refer as neuroplasticity. The continuous generation of cohorts of new neurons in some discrete regions of the adult brain, including the olfactory system, is a newly recognized form of neuroplasticity that has been recently the focus of neuroscience studies. Several lines of evidence indicate that this recruitment of newly-generated neurons is extremely sensitive to the overall neuronal activity of the host circuits. Therefore, adult neurogenesis represents, not only a constitutive replacement mechanism for lost neurons, but also a process supporting a capacity of neural plasticity in response to specific experience throughout life. The remarkable complexity of the social life offers a host of daily challenges that require a diversity of brain mechanism to make sense of the ever-changing social world. This review describes some recent findings which have begun to define reciprocal relationships between the production and integration of newborn neurons in the adult brain and social behavior. These studies demonstrate how this domain of research has the potential to address issues in the functional contribution of adult neurogenesis in the expression of some social traits as well in the role of some social contexts to finely regulate the production, survival and integration of adult newborn neurons.

Disruption of Adult Neurogenesis in the Olfactory Bulb Affects Social Interaction but not Maternal Behavior

Adult-born neurons arrive to the olfactory bulb (OB) and integrate into the existing circuit throughout life. Despite the prevalence of this phenomenon, its functional impact is still poorly understood. Recent studies point to the importance of newly generated neurons to olfactory learning and memory. Adult neurogenesis is regulated by a variety of factors, notably by instances related to reproductive behavior, such as exposure to mating partners, pregnancy and lactation, and exposure to offspring. To study the contribution of olfactory neurogenesis to maternal behavior and social recognition, here we selectively disrupted OB neurogenesis using focal irradiation of the subventricular zone in adult female mice. We show that reduction of olfactory neurogenesis results in an abnormal social interaction pattern with male, but not female, conspecifics; we suggest that this effect could result from the inability to detect or discriminate male odors and could therefore have implications for the recognition of potential mating partners. Disruption of OB neurogenesis, however, neither impaired maternal-related behaviors, nor did it affect the ability of mothers to discriminate their own progeny from others.

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

Significance The olfactory bulb (OB) receives newly born neurons through adulthood. This process constitutes another means, in addition to molecular or synaptic changes within individual neurons, by which the OB can make changes to its functional circuitry. In this study, we show that adult-born OB neurons display adaptive changes in response to the sensory context. In a restricted domain of the dendritic arbor of adult-born neurons, we found that structural and functional changes are strongest when olfactory cues are associated with a reward. Thus, the recruitment of adult-born neurons should be seen as a form of metaplasticity that strengthens long-range functional connectivity in the olfactory system during learning. The production of new neurons in the olfactory bulb (OB) through adulthood is a major mechanism of structural and functional plasticity underlying learning-induced circuit remodeling. The recruitment of adult-born OB neurons depends not only on sensory input but also on the context in which the olfactory stimulus is received. Among the multiple steps of adult neurogenesis, the integration and survival of adult-born neurons are both strongly influenced by olfactory learning. Conversely, optogenetic stimulation of adult-born neurons has been shown to specifically improve olfactory learning and long-term memory. However, the nature of the circuit and the synaptic mechanisms underlying this reciprocal influence are not yet known. Here, we showed that olfactory learning increases the spine density in a region-restricted manner along the dendritic tree of adult-born granule cells (GCs). Anatomical and electrophysiological analysis of adult-born GCs showed that olfactory learning promotes a remodeling of both excitatory and inhibitory inputs selectively in the deep dendritic domain. Circuit mapping revealed that the malleable dendritic portion of adult-born neurons receives excitatory inputs mostly from the regions of the olfactory cortex that project back to the OB. Finally, selective optogenetic stimulation of olfactory cortical projections to the OB showed that learning strengthens these inputs onto adult-born GCs. We conclude that learning promotes input-specific synaptic plasticity in adult-born neurons, which reinforces the top-down influence from the olfactory cortex to early stages of olfactory information processing.

Making scents of olfactory neurogenesis

Olfaction was long considered to belong more to the realm of art than to that of science. As a result, how the brain perceives, discriminates, and recognizes odorant molecules is still a mystery. Recent progress has nonetheless been made at early stages of the olfactory pathway when olfactory studies entered into the molecular era to elucidate the first contact of an odor molecule with a receptor. Our group focuses on the analysis of odor information in the olfactory bulb, the first processing relay in the mammalian brain. Using this model, we are attempting to decipher the code for odorant information. Furthermore, the olfactory bulb also provides an attractive model to investigate neuronal proliferation, differentiation, migration, and neuronal death, processes involving an interplay between genetic and epigenetic influences. Finally, our goal is to explore the possible consequences of the olfactory bulb plasticity, in olfactory performance. For these purposes, we aim to combine morphological, electrophysiological and behavioral approaches to investigate: (1) how the olfactory bulb processes odor molecule information, (2) how neural precursors differentiate into olfactory bulb interneurons, (3) how these newly-generated neurons integrate into an operational neural network, (4) what role they play in the adult olfactory bulb, and (5) how are basic olfactory functions maintained in such a sensory system subjected to continuous renewal of a large percentage of its neuronal population. These questions should provide new fuel for the molecular and cellular bases of sensory perception and shed light onto cellular bases of learning and memory.

Adult-Born Neurons in the Olfactory Bulb: Integration and Functional Consequences

The generation of new neurons is sustained throughout life in the olfactory system. In recent years, tremendous progress has been made toward understanding the proliferation, differentiation, migration, and integration of newborn neurons in the olfactory bulb. Here, we discuss recent findings that shed light on different aspects of the integration of adult-born neurons into olfactory circuitry and its significance for behavior.

Social regulation of reproduction in the female mound-builder mouse (Mus spicilegus)

Social environment influences the reproductive physiology and sexual behaviour of the female house mouse Mus musculus. An all-female environment tends to suppress the oestrous cycles, whereas the presence of a male induces and synchronises sexual receptivity. However, reproductive responses to social environment may differ among the various species of rodents. In mound-builder female mice, Mus spicilegus, periods of sexual receptivity are interrupted by periods where adult females display a vaginal closure. We investigated the influence of different social environments on the vaginal opening and oestrous state of adult female M. spicilegus. Result showed that when females were grouped their vaginas were generally closed but that vaginal opening occurred when they were isolated or housed with a sexual partner. Females became sexually receptive when housed with a male, but when isolated their cervical smears did not reach characteristics of the oestrus. In female M. spicilegus, male presence thus has a stimulating effect on oestrous induction. Furthermore, cohabitation with females has an inhibiting effect on vaginal opening.

Adult Neurogenesis in the Olfactory System Shapes Odor Memory and Perception

The olfactory system is a dynamic place. In mammals, not only are sensory neurons located in the sensory organ renewed through adult life, but also its first central relay is reconstructed by continuous neuronal recruitment. Despite these numerous morphological and physiological changes, olfaction is a unique sensory modality endowed with a privileged link to memory. This raises a clear conundrum; how does the olfactory system balance its neuronal turnover with its participation in long-term memory? This review concentrates on the functional aspects of adult neurogenesis, addressing how the integration of late-born neurons participates in olfactory perception and memory. After outlining the properties of adult neurogenesis in the olfactory system, and after describing their regulation by internal and environmental factors, we ask how the process of odorant perception can be influenced by constant neuronal turnover. We then explore the possible functional roles that newborn neurons might have for olfactory memory. Throughout this review, and as we concentrate almost exclusively on mammalian models, we stress the idea that adult neurogenesis is yet another form of plasticity used by the brain to copes with a constantly changing olfactory world.