Photoperiod Impacts Nucleus Accumbens Dopamine Dynamics

Abstract

Circadian photoperiod, or day length, changes with the seasons and influences behavior to allow animals to adapt to their environment. Photoperiod is also associated with seasonal rhythms of affective state, as evidenced by seasonality of several neuropsychiatric disorders. Interestingly, seasonality tends to be more prevalent in women for affective disorders such as Major Depressive Disorder and Bipolar Disorder. However, the underlying neurobiological processes contributing to sex-linked seasonality of affective behaviors are largely unknown. Mesolimbic dopamine input to the nucleus accumbens (NAc) contributes to the regulation of affective state and behaviors. Additionally, sex differences in the mesolimbic dopamine pathway are well-established. Therefore, we hypothesize that photoperiod may drive differential modulation of NAc dopamine in males and females. Here, we used fast-scan cyclic-voltammetry (FSCV) to explore whether photoperiod can modulate sub-second dopamine signaling dynamics in the NAc core of male and female mice raised in seasonally relevant photoperiods. We found that photoperiod modulates dopamine signaling in the NAc core, and that this effect is sex-specific to females. Both release and uptake of dopamine were enhanced in the NAc core of female mice raised in long, summer-like photoperiods, whereas we did not find photoperiodic effects on NAc core dopamine in males. These findings uncover a potential neural circuit basis for sex-linked seasonality in affective behaviors.Significance StatementDay length, or photoperiod, is a reliable indicator of the changing seasons, and is a powerful environmental cue influencing affective state and behavior. While studies have shown that photoperiod can modulate neurotransmitter systems involved in affective behavior, like the dopamine system, there are few studies examining effects of photoperiod on the synaptic level. Here we assess mesolimbic dopamine dynamics in mice maintained in seasonal photoperiods. We found a sex-specific effect wherein photoperiod modulates dopamine release from and uptake in dopaminergic terminals in the nucleus accumbens core of female mice with long summer-like photoperiods increasing dopamine release, thus uncovering a potential synaptic basis for sex-linked seasonality in affective behaviors.

Kappa opioid receptor agonist U50,488 inhibits dopamine more in caudal than rostral nucleus accumbens core

“…A previous study using rats has shown sex differences in magnitude of DA release between males and females, with evoked accumbal DA release being greater in females compared with males because of greater DA synthesis in females 33,48,49 . However, these studies were all done in rats, whereas our work here and others carried out in mice have found no sex differences 50 . The lack of differences in DA uptake across the rostro‐caudal axis and across sexes suggests that there is no difference in DAT expression or function.…”

Dopamine Transporter Availability in Early Parkinson's Disease is Dependent on Sunlight Exposure

“…16 Interestingly, a recent study showed that mice maintained in a long, summer-like photoperiod showed higher dopamine release in the ventral striatum as compared to the control condition. 17 Extrapolating this finding to humans, one may speculate that higher synaptic dopamine is by higher DAT expression. Seasonal oscillations in the dopaminergic system in PD have also previously been shown using [ 18 F]F-DOPA PET with right putaminal dopamine synthesis capacity being 15% higher when the patients were scanned in autumn/winter compared to spring/summer.…”

“…The DAT plays a major role in the regulation of synaptic dopamine levels by taking up synaptic dopamine back into dopaminergic neurons 16 . Interestingly, a recent study showed that mice maintained in a long, summer‐like photoperiod showed higher dopamine release in the ventral striatum as compared to the control condition 17 . Extrapolating this finding to humans, one may speculate that higher synaptic dopamine is compensated by higher DAT expression.…”

Gene expression plasticity of the mammalian brain circadian clock in response to photoperiod

“…Here we have used RNAseq to characterize differential gene rhythmicity and differential gene expression in response to Short winter-like photoperiods vs. Long summer-like photoperiods. To best capture the impact of photoperiod, we used a strain of mice (C3Hf+/+, Baba et al, 2009) which possess intact melatonin signaling, and we used perinatal exposure to photoperiods, which we have previously shown to produce robust plasticity in the SCN and robust photoperiodic responses in downstream serotonergic and dopaminergic brain circuits (Ciarleglio et al, 2010;Giannoni-Guzmán et al, 2020;Green et al, 2015;Jameson et al, 2023;Siemann et al, 2019Siemann et al, , 2020. Our approach reveals specific gene expression changes in SCN neuropeptide signaling and light response genes as candidate novel molecular mechanisms for SCN light response plasticity and SCN neural network reconfiguration in photoperiodic entrainment.…”