Laboratory animals frequently live in a relatively constant habitat, lacking many of the external factors that can influence their biology. Several studies have demonstrated increased AHN in laboratory rodents in response to enriched environments (Kempermann et al., 1997b, 1998; Nillson et al., 1999; Brown et al., 2003). Habitat complexity increases the need for behavioral flexibility (Amrein, 2015), thus free-living rodent species living in very complex habitats have been shown to exhibit much higher neurogenesis compared to animals that inhabit less complex habitats (Amrein et al., 2007; Garthe et al., 2009; Cavegn et al., 2013).

The social environment of laboratory animals can exert both positive and negative effects on neurogenesis, depending on the circumstances. Laboratory rodents such as mice and rats are typically communal species and social interactions have been shown to significantly affect the regulation of adult neurogenesis in the hippocampus (Fowler et al., 2008; Lieberwirth and Wang, 2012). Social status can influence the rate of neurogenesis where, in laboratory rodents, animals with a higher status typically show more neurogenesis than the ones with a lower social status (Gould et al., 1997, 1998; Kozorovitskiy and Gould, 2004; Thomas et al., 2007; Wu et al., 2014). Variation in estrogen levels may be the underlying mechanism responsible for differences in AHN between dominant and subordinate animals. Dominant animals typically have a higher probability of breeding, and breeding individuals usually exhibit higher levels of estrogen. Estrogen has been shown to play a role in proliferation, the survival as well as the activation of the new neurons (Fowler et al., 2008). Following ovariectomy, AHN was reduced but this could be reversed by estrogen replacement (Tanapat et al., 1999). Cell proliferation in the dentate gyrus (DG) of the hippocampus of laboratory rat females also fluctuates according to the estrous cycle, with higher cell proliferation when more estrogen is present (Tanapat et al., 1999).

Stress hormones can have positive or negative effects on AHN, depending on the type of stressor and whether the stress is acute or chronic (Schoenfeld and Gould, 2012). High levels of corticosterone in response to social isolation causes a reduction in neurogenesis and also decreases performance in other behavioral tests (Stranahan et al., 2006). This effect seems to be larger in females compared to males (Westenbroek et al., 2004). In contrast, exercise (running) induces lower levels of corticosterone and is associated with an increase in AHN (Stranahan et al., 2006).

Age is commonly viewed as a potent negative regulator of AHN since there is a dramatic decline in neurogenesis that appears to be age related in most mammals investigated, laboratory rodents included (Kuhn et al., 1996; Amrein et al., 2004; Ben Abdallah et al., 2010). This downregulation of neurogenesis is not correlated with the environment or other species-specific traits such as longevity or developmental strategy (Amrein et al., 2004). Technically, this decrease occurs relatively early in life, after which the level of neurogenesis remains relatively stable.

A vast number of studies suggest a link between learning, memory, and adult neurogenesis. Initial studies showed that learning increases hippocampal neurogenesis (Gould et al., 1999a,b) which accordingly enhances spatial memory (Snyder et al., 2005; Winocur et al., 2006). In turn, learning impairments are associated with a reduction in hippocampal neurogenesis (Lemaire et al., 2000). However, more recent evidence suggests that this is highly species and context dependent and the results are not always consistent (Dobrossy et al., 2003; Jaholkowski et al., 2009; Groves et al., 2013; Duarte-Guterman et al., 2015). In some cases, neurogenesis has no effect on spatial memory at all (Groves et al., 2013). The mixed results may be attributed to the type of behavioral tests performed or the history and age of the animals, or a combination of factors.

Habitat complexity, or the lack thereof, can influence AHN in rodents depending on the need for behavioral flexibility (Amrein, 2015). Laboratory rodents have probably adapted to their relatively uniform and confined laboratory habitat over many generations in captivity, with accompanying alterations in behavioral needs (Toth et al., 2011). Although in a different spatial context, the sealed burrow systems of mole-rats is devoid of light and lack many other sensory cues available to aboveground living rodents (Burda et al., 1990). Mole-rats thus present a model that naturally inhabits a uniform environment. In addition, even the simplistic environment of mole-rats shows interspecific variation in terms of length and complexity of the tunnels, depending on the social structure of the species, presenting opportunity for comparisons.

Laboratory mice and rats are generally classified as social and polygamous but the social structure is not rigidly fixed (Lund, 1975; Hedrich, 2012). As a taxonomic group, mole-rats show much more diverse and complex social organizations compared to laboratory animals. Bathyergids exhibit a spectrum of sociality within a single taxonomic family, ranging from strictly solitary to highly social species (Faulkes et al., 1997). Solitary species are typically polygamous whereas social species tend to be more monogamous. Social mole-rats live in family groups that exhibit a distinct reproductive division of labor (Jarvis, 1981; Bennett, 1988). Reproduction is restricted to a single female and one or two males, while the remainder of the colony comprises overlapping generations of subordinate animals that are reproductively suppressed. Mole-rats breed cooperatively, and the non-breeding individuals assist with the rearing of offspring and maintenance of the tunnel system (Jarvis, 1981; Bennett, 1988). Social mole-rat colonies exhibit linear dominance hierarchies where larger animals are dominant over smaller animals (Jacobs et al., 1991), but breeding animals are always dominant over non-breeding animals. In other rodents, both dominance and reproductive status have been shown to influence AHN (Tanapat et al., 1999; Kozorovitskiy and Gould, 2004). Therefore, the difference in social structures between species and the within species status differences in the mole-rat model provide abundant opportunities for empirical testing of predictions in a comparative setting.

Laboratory mice and rats have maximum lifespans of under 5 years (Gorbunova et al., 2008), whereas their free-living counterparts may have a much shorter life expectancy. Similar sized mole-rats, especially the social species, can attain ages three to six-fold that of laboratory animals. In captivity, the age of 16 years have been recorded for social Fukomys mole-rats (Dammann et al., 2011) and the age of 32 years for naked mole-rats (Heterocephalus glaber) (Buffenstein and Jarvis, 2002). An exponential decline in AHN is apparent in both long and short-lived species, but the slower maturation of longer lived species may offer a larger window for experimental manipulation of the baseline AHN.

The lower survival rate of young neurons in mole-rats supports a habitat-dependent modulation of neurogenesis. The habitat complexity of mole-rat burrow systems is very low when compared to the highly complex three-dimensional environments of surface dwelling rodents. The sealed burrow systems of mole-rats lack external cues and therefore present a very homogenous and stable habitat (Burda et al., 1990).

Despite the overall low habitat complexity, the length and complexity of mole-rat burrows differ between species, it depends on a number of factors including sociality, habitat type, resource availability, and population density (Le Comber et al., 2002). The burrow systems of Damaraland mole-rats (Fukomys damarensis) can reach up to 2 km in length (Bennett and Faulkes, 2000), while burrow systems of solitary species such as the Cape mole-rat (Georychus capensis) are generally much shorter (Thomas et al., 2012). Within the context of the subterranean niche, interspecies differences in hippocampal neurogenesis that is consistent with the relative length and complexity of the burrows of the different species, is evident. The social and solitary species have similar numbers of granule cells despite size differences in the species [Cape: 150–200 g; Highveld (Cryptomys hottentotus pretoriae; intermediately social species): 80–120 g; Damaraland: 120–150 g; Bennett and Faulkes, 2000, pers. obs.], however both the Highveld and Damaraland mole-rats have more proliferating cells compared to Cape mole-rats (Ki67 staining) (Amrein et al., 2014; Oosthuizen and Amrein, 2016). The numbers of young neurons show large within species variation, thus young neuron numbers of the individual species show some overlap.

Despite the low rate of neurogenesis, a status dependent amount of hippocampal neurogenesis is evident in the social Damaraland mole-rats. Seemingly in contrast with results from laboratory rodents, the breeding females, or queens, have lower numbers of both proliferating cells and young neurons compared to subordinate colony members (Oosthuizen and Amrein, 2016) (Figure 2). A similar occurrence is observed in the naked mole-rat, where breeding animals were found to have significantly less young neurons, as visualized by doublecortin (DCX) immunoreactive neurons, compared to the non-breeding animals (Peragine et al., 2014). Differential AHN in breeding and non-breeding mole-rats may potentially have an endocrinological basis. Both reproductive hormones and stress hormones have been shown to modulate neurogenesis in laboratory rodents (Cameron and Gould, 1994; Gould and Tanapat, 1999; Tanapat et al., 1999).

In highly social species such as the Damaraland mole-rat and the naked mole-rat, the breeding females have higher estrogen levels compared to non-breeding animals (Bennett and Jarvis, 1988; Faulkes et al., 1990; Bennett, 1994), thus one would also expect an upregulation of neurogenic cells, yet the opposite is true (Peragine et al., 2014; Oosthuizen and Amrein, 2016). In the case of mole-rats, estrogen appears to rather downregulate AHN. Similarly, cell proliferation is inhibited in the dentate gyrus of female meadow voles in the breeding season, when high estrogen levels are present, compared to females out of the breeding season, although more cells survive in the reproductively active females (Galea and McEwen, 1999; Ormerod and Galea, 2001). A potential mechanism for the disparity in the effect of estrogen on AHN may be related to the density of the estrogen receptor α in the dentate gyrus. In voles, estrogen increased the density of the estrogen receptor α (ERα) (Fowler et al., 2005), however this increase was region specific and no difference was observed in the dentate gyrus. In mole-rats, non-breeding Damaraland mole-rat females express lower levels of ERα compared to the breeders in brain regions important for reproduction (Voigt et al., 2014). The density of the ERα has not been investigated in the DG of mole-rats thus far, but could potentially also show differential expression between breeder and non-breeder mole-rats. In naked mole-rats, no significant relationships could be identified between circulating gonadal steroids and DCX (Peragine et al., 2014), however this do not exclude potential differences in proliferating cells or receptors for the hormones.

Stress hormones have not been exhaustively investigated in mole-rats in terms of social status in the colony. It appears that when the social structure is stable, there is no difference cortisol levels between breeding and non-breeding animals (Clarke and Faulkes, 1998; Clarke et al., 2001), but instability in the social structure is associated with increased cortisol levels in non-breeding animals compared to the breeding animals (Clarke and Faulkes, 1997). In congruence with this, a higher concentration of CRF receptor binding sites is present in non-breeding naked mole-rats (Beery et al., 2016). In addition, CRF receptor binding sites also differ between solitary and social mole-rat species (Coen et al., 2015), where differences in proliferating cells have been shown. Stress hormones are also expressed in response to running and exercise, where it is associated with an upregulation of AHN (Stranahan et al., 2006). Non-breeding Damaraland mole-rat females show higher levels of locomotor activity than the breeding females (Oosthuizen and Bennett, 2015), therefore increased activity could, at least in part, explain the higher AHN in non-breeding mole-rats.

In agreement with their increased life expectancies, mole-rats have long gestation times and subsequent postnatal development is slower than other rodents. Like other animals, mole-rats also show a steep decline in neurogenesis at a relatively young age (Penz et al., 2015). A slow postnatal development may increase the expected window for higher levels of neurogenesis seen in all young animals between birth and puberty (Penz et al., 2015). In mole-rats, puberty is reached around the age of 1 year, when neurogenesis should start to decline exponentially (Bennett and Faulkes, 2000; Penz et al., 2015), however this has not been tested empirically.

As a result of their lightless environment, subterranean animals rely on other mechanisms such as tactile stimuli and memory to navigate their burrow systems (du Toit et al., 2012). Despite the relatively uniform habitat of the sealed tunnel systems, the difference in tunnel length and complexity appears to be sufficient stimulation to induce learning differences in the different species. Damaraland mole-rats with longer and more complex burrow systems, show superior learning abilities compared to the solitary Cape mole-rat (Costanzo et al., 2009; Oosthuizen et al., 2013), Oosthuizen, unpublished data). The enhanced learning abilities of Damaraland mole-rats are associated with more proliferating cells compared to Cape mole-rats (Amrein et al., 2014; Oosthuizen and Amrein, 2016). Although the basal level of neurogenesis differs with social status in highly social species, there is no corresponding difference in learning abilities.

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.