Social Cues, Adult Neurogenesis, and Reproductive Behavior

Adult neurogenesis is a striking form of neural plasticity occurring in restricted regions of the mammalian brain. The past decades have witnessed tremendous research efforts in this field providing significant information regarding the anatomical, molecular, and functional mechanisms underlying neurogenesis in the adult brain. New neuron production regulates integrated brain functions, learning and memory, and adapts the brain to the changing world. Recent data in rodents indicates a link between adult neurogenesis and reproductive and social behavior. This provides the opportunity to unravel the function of this form of neural plasticity in ethologically relevant contexts and opens new perspectives to explore how the brain processes social stimuli. In this chapter we will summarize some of the major key points regarding the cues and mechanisms modulating adult neurogenesis during social interaction and possible role/s played by newborn neurons in this context. To achieve this goal we will give an overview of past and ongoing literature showing this link, with particular emphasis on our recent studies on two examples of sexual behavior: mate pheromonal imprinting in female mice, and paced mating in rats. The early conception of the function of the brain postulated that once the brain developed it became stable and no new neurons were added in adulthood. This dogma has gradually been dropped over the past 40 years with the clear demonstration that adult neurogenesis is a striking form of structural remodeling characterizing the brain of vertebrates, though with significant differences between groups (Lindsey and Tropepe 2006; Bonfanti and Peretto 2011). In the 1970s, the issue of adult neurogenesis was regarded with skepticism although during the previous decade some proliferative activity was reported in the brain by Altman and colleagues (Altman 1963; Altman and Das 1965). Only years later, with the progress of neuroanatomical techniques and the demonstration of genesis and integration of new neurons in the adult brain of canaries (Nottebohm 1985), adult neurogenesis regained attention. A new era in this field occurred starting from two simultaneous findings: the occurrence of a massive cell migration toward the rodents’ olfactory bulb (Luskin 1993; Lois and Alvarez-Buylla 1994) and the first isolation of adult neural stem cells (Reynolds and Weiss 1992). These studies strengthened the idea that neural plasticity in adult mammals not only occurs through synaptic remodeling but also through the addition of new neurons in the mature preexisting circuits. During the last two decades, this intriguingly persisting process in the mammalian brain was intensely investigated, and several review articles progressively made the point on its extension, features, and significance under physiological and pathological conditions (Emsley et al. 2005; Sohur et al. 2006; Gould 2007; Migaud et al. 2010; Bonfanti and Peretto 2011; Curtis et al. 2011; Fuentealba et al. 2012). It is now clear that a constitutive/physiologic neurogenesis in adult mammals mostly occurs within two telencephalic regions, the subventricular zone–olfactory bulb system (SVZ-OB) (Lois and Alvarez-Buylla 1994) and the subgranular zone (SGZ) of dentate gyrus (DG) of the hippocampus (Kempermann et al. 2004). The neurogenic process in these regions is orchestrated by a complex interplay between intrinsic and extrinsic environmental cues. Several developmental signals, morphogens, growth factors, neurotransmitters, hormones, transcription factors, and epigenetic regulators have been described to tightly regulate specification and activity of proliferating progenitors, as well as the migration and integration of neuronal precursors within functional circuits (Hagg 2005; Faigle and Song 2013). The signaling mechanisms supporting adult neurogenesis are dynamically regulated by many environmental cues that can either positively or negatively influence the neurogenic process at the level of progenitor cells and during the integration of newborn neurons within circuits (Ma et al. 2009). This activity-dependent regulation is only beginning to be unraveled. Importantly, adult-born neurons in neurogenic regions exhibit critical periods of plasticity during a specific time window of their maturation (Nissant et al. 2009; Ming and Song 2011), and high responsiveness toward the same stimuli driving their integration/selection into circuits (Magavi et al. 2005; Kee et al. 2007). This supports a role of newborn neurons in sensory processing in DG and OB. Accordingly, several sources of data indicate that adult neurogenesis contributes to mechanisms of learning and memory (Lazarini et al. 2009; Moreno et al. 2009), and more recent hypotheses suggest that it also contributes to enhancing pattern separation (Aimone et al. 2011; Sahay et al. 2011). In this view, the continuous addition of new neurons in the olfactory bulb and hippocampus rather than being a simple mechanism of renewal of preexisting cells expands the capacity for plasticity in these regions. In this chapter we will describe recent findings (see Feierstein et al. 2012 for review) that link reproductive and social stimuli to adult neurogenesis, particularly in the olfactory system. We will address first a brief description of the main results supporting this connection, and then, taking into account our recent work (Oboti et al. 2009, 2011; Corona et al. 2011; Portillo et al. 2012), we will focus on two striking examples of sexual behavior: (1) mate pheromonal imprinting to avoid pregnancy block in female mice and (2) paced mating in rats, namely the ability to control the sexual interaction. In both cases we demonstrate a link between adult neurogenesis and social activities underlying the reproductive function.