The hippocampus (HPC) and prefrontal cortex (PFC) are both necessary for learning and memory-guided behavior. Multiple direct and indirect anatomical projections connect the two regions, and HPC - PFC functional interactions are mediated by diverse physiological network patterns, thought to sub serve various memory processes. Disconnection experiments using contralateral inactivation approaches have established the role of direct, ipsilateral projections from ventral and intermediate HPC (vHPC and iHPC) to PFC in spatial memory. However, numerous studies have also prominently implicated physiological interactions between dorsal HPC (dHPC) and PFC regions in spatial memory tasks, and recent reports have identified direct dHPC - PFC connections. Whether dHPC - PFC interactions are necessary for spatial learning and memory has yet to be tested. Here, we used a chemogenetic inactivation approach using virally-expressed DREADDs (designer receptors exclusively activated by designer drugs) in rats to investigate the role of dHPC - PFC interactions in learning a hippocampal - dependent spatial alternation task. We implemented a rapid learning paradigm for a continuous W-track spatial alternation task comprising two components: an outbound, working memory component, and an inbound, spatial reference memory component. We investigated the effect of contralateral inactivation of dHPC and PFC on learning this task as compared with naïve and vehicle injection controls, as well as ipsilateral inactivation of the same regions. Contralateral dHPC - PFC inactivation selectively led to a significant impairment in learning the spatial working memory task compared to control groups, but did not impair learning of the spatial reference memory task. Ipsilateral inactivation animals showed similar learning rates as animals in the control groups. In a separate experiment, we confirmed that bilateral inactivation of PFC also leads to an impairment in learning the spatial working memory task. Our results thus demonstrate that dHPC - PFC interactions are necessary for spatial alternation learning in novel tasks. In addition, they provide crucial evidence to support the view that physiological interactions between dHPC and PFC play a key role in spatial learning and memory.

Newborns and hatchlings can perform incredibly sophisticated behaviors, but many animals abstain from sexual activity at the beginning of life. Hormonal changes have long been known to drive both physical and behavioral changes during adolescence, leading to the largely untested assumption that sexuality emerges from organizational changes to neuronal circuitry. We show that the transition to sexuality in male Drosophila is controlled by hormonal changes, but this regulation is functional rather than structural. In very young males, a broadly acting hormone directly inhibits the activity of three courtship-motivating circuit elements, ensuring the complete suppression of sexual motivation and behavior. Blocking or overriding these inhibitory mechanisms evokes immediate and robust sexual behavior from very young and otherwise asexual males. Similarities to mammalian adolescence suggest a general principle in which hormonal changes gate the transition to sexuality not by constructing new circuitry but by permitting activity in otherwise latent motivational circuit elements.

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