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 (Ruffino, Salo, Koivisto, Banks, &
Korpimäki, 2014; Schneider, 2004), 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 (Caro, Schaper, Hut, Ball, & Visser, 2013;
Hut, Dardente, & Riede, 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 (Guillemin, 1977;
Schally et al., 1970). 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, McManus, Goodman, & Jansen, 2011), and express
RF-amides: Kisspeptin (Kiss1 ) (Smith, Cunningham, Rissman,
Clifton, & Steiner, 2005; Smith, Dungan, et al., 2005) and RF-amide
related peptide (Rfrp3 ), which are candidates for integrating
environmental cues, mediating seasonal reproductive responses (Klosen,
Sébert, Rasri, Laran-Chich, & Simonneaux, 2013; Krebs, Fischaleck, &
Blum, 2009; Revel, Saboureau, Pévet, Simonneaux, & Mikkelsen, 2008;
Simonneaux, Ancel, Poirel, & Gauer, 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, Pallas 1778 and tundra vole,Microtus oeconomus , Pallas 1776). 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, van Dalum, Hazlerigg, & Hut, 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; Ergon, Lambin, &
Stenseth, 2001; Negus & Berger, 1977; R J Nelson, Dark, & Zucker,
1983; Sanders, Gardner, Berger, & Negus, 1981). 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, Pilorz, Boerema, Strijkstra, & Daan, 2011; Vincent 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.