The laboratory mouse serves as an important model system for studying gene, brain and behavioural interactions. Powerful methods of gene targeting have helped to decipher gene-function associations in human diseases. Yet, the laboratory mouse, obtained after decades of human-driven artificial selection, inbreeding, and adaptation to captivity, is of limited use for the study of fitness-driven behavioural responses that characterize the ancestral wild house mouse. Here, we demonstrate that the backcrossing of wild mice with knockout mutant laboratory mice retrieves behavioural traits exhibited exclusively by the wild house mouse, thereby unmasking gene functions inaccessible in the domesticated mutant model. Furthermore, we show that domestication had a much greater impact on females than on males, erasing many behavioural traits of the ancestral wild female. Hence, compared with laboratory mice, wild-derived mutant mice constitute an improved model system to gain insights into neuronal mechanisms underlying normal and pathological sexually dimorphic social behaviours.

The hippocampus and the striatum are thought to play distinct roles in learning and memory, each supporting an independent memory system. A fundamental question is whether, and how, these systems interact to jointly contribute to learning and memory. In particular, it remains unknown whether the striatum contributes selectively to implicit, habitual learning, or whether the striatum may also contribute to long-term episodic memory. Here, we show with functional magnetic resonance imaging (fMRI) that the hippocampus and the striatum interact cooperatively to support episodic memory formation. Participants were scanned during a memory encoding paradigm and, subsequently, were tested for memory of encoded items. fMRI data revealed that successful memory was associated with greater activity in both the hippocampus and the striatum (putamen) during encoding. Furthermore, activity in the hippocampus and the striatum was correlated within subjects for items that were later remembered, but not for items that were forgotten. Finally, across subjects, the strength of the correlation between the hippocampus and the striatum predicted memory success. These findings provide novel evidence for contributions of both the striatum and the hippocampus to successful episodic encoding and for a cooperative interaction between them.

The prefrontal cortex (PFC) plays an important role in regulating social functions in mammals, and impairments in this region have been linked with social dysfunction in psychiatric disorders. Yet little is known of how the PFC encodes social information and of how social representations may be altered in such disorders. Here, we show that neurons in the medial PFC (mPFC) of freely behaving mice preferentially respond to socially-relevant sensory cues. Population activity patterns in the mPFC differed considerably between social and nonsocial stimuli and underwent experience-dependent refinement. In Cntnap2 knockout mice, a genetic model of autism, both the categorization of sensory stimuli and the refinement of social representations were impaired.Noise levels in spontaneous population activity were higher in Cntnap2 mice, and correlated strongly with the degree to which social representations were disrupted. Our findings elucidate the encoding of social sensory cues in the mPFC, and provide an important link between altered prefrontal dynamics and autism-associated social dysfunction.

Recent brain imaging research has highlighted a new global system of areas termed the Default Mode network (DM), which appears to specialize in intrinsically oriented functions. However, it is still unresolved to what extent this system contains functional subsystems as in the better known sensory and motor cortices. Here, we report that functional subdivisions can be revealed within individual nodes of the DM, such as the Inferior Parietal Lobule (IPL), through the use of different categories of self-oriented tasks. Subjects underwent BOLD fMRI scans during which they were asked to recall self-related positive and negative information in the categories of people and food. These tasks elicited distinct regions of activation within the DM. Importantly, the observed activations were above the activity level in the baseline, no-task condition for these regions. The main subdivision within the DM was observed in the inferior and posterior parietal cortex. Analysis of coherent resting state fluctuations (functional connectivity analysis) revealed that these regions of activation were part of a distinct network of regions within the DM. These results argue against viewing the DM as a unitary system, and are compatible with the notion that, similar to the rest of the cerebral cortex, the DM consists of distinct, functionally specialized subregions.

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The prefrontal cortex (PFC) plays an important role in regulating social functions in mammals, and impairments in this region have been linked with social dysfunction in psychiatric disorders. Yet little is known of how the PFC encodes social information and of how social representations may be altered in such disorders. Here, we show that neurons in the medial PFC (mPFC) of freely behaving mice preferentially respond to socially-relevant sensory cues. Population activity patterns in the mPFC differed considerably between social and nonsocial stimuli and underwent experience-dependent refinement. In Cntnap2 knockout mice, a genetic model of autism, both the categorization of sensory stimuli and the refinement of social representations were impaired.Noise levels in spontaneous population activity were higher in Cntnap2 mice, and correlated strongly with the degree to which social representations were disrupted. Our findings elucidate the encoding of social sensory cues in the mPFC, and provide an important link between altered prefrontal dynamics and autism-associated social dysfunction.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

The vomeronasal organ (VNO) specializes in detection of chemosignals, mainly pheromones, which control social communication and reproduction in many mammals. These pheromones must solubilize with nasal fluids before entering the VNO, and it was suggested that they are delivered to and cleared from the VNO by active pumping. Yet, the details of this pheromone delivery process are unclear. In this study, we first constructed a high-resolution 3D morphological image of the whole adult mouse snout, by using ultra-high-resolution micro-CT. We identified a net of micro tunnels starting from the nostrils and extending around and through the VNO. These micro tunnels connect the nasal cavity with the VNO and the oral cavity via the nasopalatine ducts (NPD). Other micro tunnels connect the nasal cavity to the main olfactory epithelium. We next demonstrated that physical obstruction of the NPD severely impairs the clearance of dissolved compounds from the VNO lumen. Moreover, we found that mice with blocked NPD display alterations in chemosignaling-evoked neuronal activation in brain regions associated with the vomeronasal system. Finally, NPD-blocked male mice exhibit reduced preference for female chemosignals, and impaired social interaction behavior. Taken together, our findings indicate that the NPD in mice are connected to both the nasal and oral cavity, serving an essential role in regulating the flow of soluble chemosignals through the VNO, and are required for proper pheromone-mediated social communication.