Introduction
Seasonal mammals time their reproduction such that offspring will be born during the most optimal time of year, when temperatures are rising and food is abundant. Because of the absence of inter-annual variation in photoperiodic cycles, many vertebrates use photoperiod as a reliable cue to synchronize intrinsic annual timing mechanisms controlling seasonal adaptation of physiology and behavior (for review, see Baker, 1938; Nakane and Yoshimura, 2019). In mammals, photoperiodic signals are perceived by retinal photoreception, and converted in the brain into melatonin signals regulating gonadal responses by the so called ‘photoperiodic neuroendocrine system’ (PNES) (for review, see: Dardente et al., 2018; Hut, 2011; Nakane and Yoshimura, 2019).
Animals that experience food scarcity reduce their overall food consumption while foraging activity is increased (van der Vinne et al. 2019). This induces a negative energy balance, in which there is less energy available for reproductive investment, because most energy ingested is needed for body tissue maintenance. Energy balance and reproduction are closely related (Schneider 2004; Ruffino et al.2014), but its regulatory mechanisms remain to be disclosed. Seasonally breeding animals, such as voles, may use a combination of photic and non-photic seasonal cues to control reproduction. Environmental factors such as ambient temperature, food availability and its behavioral foraging activity response can all affect energy balance and are expected to be involved in adaptive modification of the photoperiodic response to inhibit or accelerate reproductive development (Caroet al. 2013; Hut et al. 2014).
The neuroanatomical networks that underly integration of energy balance information into the photoperiodic response system is largely unknown. Neurons expressing gonadotropin-releasing hormone (GnRH) are known to be the main drivers of the reproductive axis controlling the release of hormones (i.e. LH, FSH) from the pituitary gland (Schally et al.1970; Guillemin 1977). Prior studies suggest that mediobasal hypothalamic (MBH) thyroid hormone triiodothyronine (T3), which is increased under long photoperiods, may not act on GnRH neurons directly, but rather via other hypothalamic areas, such as the preoptic area (POA), the dorso-/ventromedial hypothalamus (DMH/VMH) and the arcuate nucleus (ARC), which are involved in metabolic regulation (for review, see Hut et al., 2014). Neurons located in those hypothalamic regions communicate directly with GnRH neurons (Hileman et al. 2011), and express RF-amides: Kisspeptin (Kiss1 ) (Smith et al. 2005b, a) and RF-amide related peptide (Rfrp3 ), which are candidates for integrating environmental cues, mediating seasonal reproductive responses (Revelet al. 2008; Krebs et al. 2009; Klosen et al. 2013; Simonneaux et al. 2013). Kiss1 functions as a strong activator of GnRH neurons, and therefore is an important regulator of puberty onset and reproduction (De Roux et al. 2003; Seminara et al.2004).
To investigate mechanisms of adaptive modification of the photoperiodic response, we decided to use two vole species as study organisms (Common vole, Microtus arvalis and Tundra vole, Microtus oeconomus ). Voles may be the ideal species to study these questions since voles can have strong photoperiodic responses and a functional canonical PNES system (Król et al. 2012; van Rosmalen et al. 2020). On the other hand, voles are also known to be able to respond to the environment in a more opportunistic way (Daketse & Martinet 1977; Negus & Berger 1977; Sanders et al. 1981; Nelsonet al. 1983; Ergon et al. 2001). Common voles are distributed in central Europe (38-62°N), whereas Tundra voles are distributed at more northern latitudes (48-72°N). Voles from our two lab populations originate from the same latitude in the Netherlands (53°N), which is for the Common vole at the center of its latitudinal range, and for the Tundra vole at the southern boundary of its latitudinal range. For this reason, it is expected that our Common vole lab population is better adapted to the local environment at 53°N than our Tundra vole lab population, which may be better adapted to more northern latitudes. At northern latitudes, Tundra voles live under isolating snow covers for a substantial part of the year, which may make photoperiod an unreliable cue for seasonal adaptation in this species. Presumably differences in hypothalamic neurobiological mechanisms may underly the different breeding strategies of the Common and the Tundra vole.
In this study, voles were exposed to photoperiodic transitions mimicking spring, under which both ambient temperature and food availability was manipulated. By implementing the work-for-food (WFF) paradigm we can induce different levels of natural food scarcity in the laboratory leading to a negative energy balance in small rodents on a high workload (Hut et al. 2011; van der Vinne et al. 2014). We assessed how (which genes), and where in the brain photoperiodic and metabolic cues are integrated to mediate reproductive responses, and how this neurobiological system is differently shaped in two closely related vole species.