Hormonal control of motivational circuitry orchestrates the transition to sexuality in Drosophila

Abstract

10Newborns and hatchlings of many species perform incredibly sophisticated behaviors, but all 11 vertebrates and many invertebrates selectively abstain from sexual activity at the beginning of life. 12Hormonal changes have long been associated with adolescence, but it is not clear how these 13circulating factors create a new motivation and drive its associated behaviors. We show that the 14 transition to sexuality in male Drosophila is controlled by juvenile hormone, which spikes at 15 eclosion and declines over days as the propensity for courtship gradually increases. Juvenile 16hormone directly inhibits the activity of at least three courtship-motivating circuit elements, 17ensuring the complete suppression of sexual motivation and behavior. Blocking or overriding 18 these inhibitory mechanisms evokes immediate and robust sexual behavior from very young and 19 otherwise asexual males. These results provide a first example of hormonal changes gating the 20 transition to sexuality by activating latent, but largely developed and functional, motivational 21 circuitry. 22

Juvenile hormone drives the maturation of spontaneous mushroom body neural activity and learned behavior

“…JH titer is maximal around the time that adult flies eclose and then falls rapidly within the first 72 h of adulthood (Bownes and Rembold, 1987;Zhang et al, 2019), a time course similar to the observed decrease in a 0 /b 0 KC activity (Figure 1F). To gain insight into the developmental time window in which JH signaling exerts its effects on KC spontaneous activity, we restricted the knockdown of Met and Gce in KCs to an early post-eclosion period (day 0-2) or a period late in the first week of adulthood (day 4-7) with the temperature sensitive repressor tub-GAL80 ts (McGuire et al, 2003).…”

“…Specifically, we find that a 0 /b 0 KCs exhibit sensorimotor-independent, TTX-insensitive asynchronous activity in young animals that is mediated by Cac voltagegated calcium channels. JH signaling in a young animal sensitive period, when the titer of JH circulating is high (Bownes and Rembold, 1987;Zhang et al, 2019), is required to achieve the mature, low KC activity state and enhance learned behavior. Our discovery that a hormone triggers a neural activity state transition essential for robust learning provides a model for mechanistically probing the maturation of learning circuits and behavior.…”

“…JH signaling sculpts a 0 /b 0 KC activity maturation What underlying molecular mechanisms orchestrate the agedependent decrease in a 0 /b 0 KC spontaneous activity? Ecdysone and JH are essential hormonal modulators of early development and behavioral maturation (Argue et al, 2013;Bilen et al, 2013;Jindra et al, 2013;Lin et al, 2016;Marchetti and Tavosanis, 2017;Zhang et al, 2019); therefore, we hypothesized that they might serve as systemic signals that modulate KC activity with age. We found that ecdysone is dispensable for KC activity maturation, as decreasing ecdysone levels systemically (Gaziova et al, 2004) or decreasing candidate MB-expressed ecdysone receptors (Lark et al, 2017;Lee et al, 2000) specifically in KCs did not influence spontaneous activity in young or mature animals (Figures S3A-S3C).…”

Developmental plasticity in male courtship in Bicyclus anynana butterflies is driven by hormone regulation of the yellow gene

“…In insects, hormones are typically assumed to regulate sexual behavior by activating existing neural circuits that control processes such as sexual maturation, memory formation and pheromone communication (11,(27)(28)(29). Recently, it has been shown that hormones can also regulate sexual motivation by repressing activation of existing neural circuits (5). It remained unclear, however, whether exposure to different levels of hormones earlier in development could organize neural circuits that affect sexual behavior in adults.…”

“…Seasonal changes in temperature and photoperiod can serve as important cues that alter hormone levels and sexual behavior in a wide range of vertebrate and invertebrate taxa (4). Precisely how hormone signaling influences sexual behavior in most animals however, is not well known (5).…”