SummaryThe prefrontal cortex plays a critical role in adjusting an organism's behavior to its environment. In particular, numerous studies have implicated the prefrontal cortex in the control of social behavior, but the neural circuits that mediate these effects remain unknown. Here we investigated behavioral adaptation to social defeat in mice and uncovered a critical contribution of neural projections from the medial prefrontal cortex to the dorsal periaqueductal grey, a brainstem area vital for defensive responses. Social defeat caused a weakening of functional connectivity between these two areas and selective inhibition of these projections mimicked the behavioral effects of social defeat. These findings define a specific neural projection by which the prefrontal cortex can control and adapt social behavior.The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license. *Correspondence to: gross@embl.it. ** Current address: Sainsbury Wellcome Centre, University College London, UK Author contributions T.B.F. designed, performed and analyzed all experiments, except the retrograde tracer experiments that were designed, performed, and analyzed by L.M., the in vitro electrophysiology experiments that were designed, performed, and analyzed by Z.P. and T.B., the monosynaptic rabies experiment that was designed, performed, and analyzed by B.A.S., the evoked field potential experiments that were designed, performed, and analyzed by M.E.M., the Granger causality and power analyses that were carried out by Y.Z., and for some behavioral experiments and imaging that were performed and analyzed by A.K

This study of children with DD found deficits in performance on VSWM tasks, suggesting that fronto-striatal-parietal neural networks that underlie processes of attention and the executive component of VSWM are dysfunctional in children with DD. These findings further our understanding of DD and suggest more specific interventions that might improve functioning.

Recent advances in neural circuitry techniques, like optogenetics and chemogenetics, have allowed for a greater understanding of the periaqueductal gray (PAG) and its importance in predator and prey behaviors. These studies in rodents have highlighted the role of the rostrolateral PAG in hunting behaviors, and have demonstrated functional differences across the dorsal-ventral/rostral-caudal axes of the PAG associated with defensive behaviors. Human imaging studies have further demonstrated that the PAG is active during situations involving imminent threat suggesting that the function of the PAG is likely largely conserved across species. This mini-review article highlights some of the recent advancements towards our understanding of the functional neuroanatomy of the PAG and its importance in the predator and prey behaviors that are critical for survival.

In addition to memory impairments, patients with Alzheimer's disease (AD) exhibit a number of behavioural and psychological symptoms that can affect social interactions over the course of the disease. While altered social interactions have been demonstrated in a number of mouse models of AD, many models only recapitulate the initial stages of the disease, and these behavioural changes have yet to be examined over the course of disease progression. By performing a longitudinal study using the 5xFAD mouse model, we have demonstrated that transgenic females exhibit progressive alterations in social investigation compared to wild-type controls. Transgenic females exhibited an age-related reduction in interest for social odours, as well as reduced investigative behaviours towards novel conspecifics in a novel environment. However, transgenic mice exhibited no obvious olfactory deficits, nor any changes in scent-marking behaviour compared to wild-type controls, indicating that changes in investigative behaviour were due to motivation to engage with a social stimulus. This evidence suggests that transgenic 5xFAD females exhibit increased social anxiety in novel environments compared to wildtype controls. Overall, transgenic 5xFAD female mice mimic some features of social withdrawal observed in human AD patients suggesting this strain may be suitable for modelling aspects of the social dysfunction observed in human patients.Keywords social behaviors; transgenic mice; 5xFAD, Alzheimer's disease Evidence for increased sociability in the 3xTg-AD mouse model has also been presented [19], but the Tg2576 strain exhibits no effect of AD pathology on sociability [17]. Overall, these results indicate that some mouse models of AD exhibit changes in social behaviour that include altered aggression and sociability. However, many transgenic mouse models of AD (e.g., 3xTg-AD, APP/PS1, and Tg2576) exhibit a slow rate of amyloid beta (Ab) accumulation and can only model the initial phase of the disease, which does not include widespread neurodegeneration [20].By comparison, the 5xFAD strain exhibits rapid development and progression of amyloid plaques and neurodegeneration, allowing effects to be tracked across early-, mid-, and late-stage disease progression [20,21]. There is increasing evidence that 5xFAD mice exhibit a range of social deficits that, in some cases, mirror the social symptoms presented by AD patients. Transgenic 5xFAD 9-month-old male mice and 12-month-old male and female mice demonstrate deficits in nest building, a behaviour that has been associated with affiliative behaviours [22,23]; however, they also engage in more homecage social behaviours than wild-type controls [24]. Transgenic 5xFAD mice also exhibit impaired social recognition memory at 9-months of age [24], consistent with memory deficits exhibited in this strain and human AD patients.While these results suggest that the 5xFAD strain exhibit social deficits, a comprehensive investigation of social behaviours in this strain has not yet been performed. The p...

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