Explore the vast range of titles available.

Social recognition is essential for the formation of social structures. Many times, recognition comes with lesser exploration of familiar animals. This lesser exploration has led to the assumption that recognition may be a habituation memory. The underlying memory mechanisms and the thereby acquired cortical representations of familiar mice have remained largely unknown, however. Here, we introduce an approach directly examining the recognition process from volatile body odors among male mice. We show that volatile body odors emitted by mice are sufficient to identify individuals and that more salience is assigned to familiar mice. Familiarity is encoded by reinforced population responses in two olfactory cortex hubs and communicated to other brain regions. The underlying oxytocin-induced plasticity promotes the separation of the cortical representations of familiar from other mice. In summary, neuronal encoding of familiar animals is distinct and utilizes the cortical representational space more broadly, promoting storage of complex social relationships. Recognition memory for other individuals forms quickly. Here the authors show that such memories are enabled by oxytocin and can be retrieved from reinforced and more distinct neural representations even when only limited sensory information is available.

Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin’s general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.

Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach, from behavioral modeling and fMRI in task-performing mice to cellular recordings, in order to disentangle local network contributions to olfactory reinforcement learning. At mesoscale, fMRI identifies a functional olfactory-striatal network interacting dynamically with higher-order cortices. While primary olfactory cortices respectively contribute only some value components, the downstream olfactory tubercle of the ventral striatum expresses comprehensively reward prediction, its dynamic updating, and prediction error components. In the tubercle, recordings reveal two underlying neuronal populations with non-redundant reward prediction coding schemes. One population collectively produces stabilized predictions as distributed activity across neurons; in the other, neurons encode value individually and dynamically integrate the recent history of uncertain outcomes. These findings validate a cross-scale approach to mechanistic investigations of higher cognitive functions in rodents. Where and how the brain learns from experience is not fully understood. Here the authors use a hierarchical approach from behavioural modelling to systems fMRI to cellular coding reveals brain mechanisms for history informed updating of future predictions.

Silencing of dopamine transporter (DAT), a main controlling factor of dopaminergic signaling, results in biochemical and behavioral features characteristic for neuropsychiatric diseases with presumed hyperdopaminergia including schizophrenia, attention deficit hyperactivity disorder (ADHD), bipolar disorder, and obsessive-compulsive disorder (OCD). Investigation of DAT silencing thus provides a transdiagnostic approach towards a systems-level understanding of common underlying pathways. Using a high-field multimodal imaging approach and a highly sensitive cryogenic coil, we integrated structural, functional and metabolic investigations in tandem with behavioral assessments on a newly developed preclinical rat model, comparing DAT homozygous knockout (DAT-KO, N = 14), heterozygous knockout (N = 8) and wild-type male rats (N = 14). We identified spatially distributed structural and functional brain alterations encompassing motor, limbic and associative loops that demonstrated strong behavioral relevance and were highly consistent across imaging modalities. DAT-KO rats manifested pronounced volume loss in the dorsal striatum, negatively correlating with cerebellar volume increase. These alterations were associated with hyperlocomotion, repetitive behavior and loss of efficient functional small-world organization. Further, prefrontal and midbrain regions manifested opposite changes in functional connectivity and local network topology. These prefrontal disturbances were corroborated by elevated myo-inositol levels and increased volume. To conclude, our imaging genetics approach provides multimodal evidence for prefrontal-midbrain decoupling and striato-cerebellar neuroplastic compensation as two key features of constitutive DAT blockade, proposing them as transdiagnostic mechanisms of hyperdopaminergia. Thus, our study connects developmental DAT blockade to systems-level brain changes, underlying impaired action inhibition control and resulting in motor hyperactivity and compulsive-like features relevant for ADHD, schizophrenia and OCD.

22q11.2, 15q13.3, and 1q21.1 microdeletions attract considerable interest by conferring high risk for a range of neuropsychiatric disorders, including schizophrenia and autism. A fundamental open question is whether divergent or convergent neural mechanisms mediate this genetic pleiotropic association with the same behavioral phenotypes. We use a combination of rodent microdeletion models with high-field neuroimaging to perform a comparative whole-brain characterization of functional and structural mechanisms linked to high-risk states. Resting-state functional and structural magnetic resonance imaging data were acquired on mice carrying heterozygous microdeletions in 22q11.2 ( N  = 12), 15q13.3 ( N  = 11), and 1q21.1 ( N  = 11) loci. We performed network-based statistic, graph, and morphometric analyses. The three microdeletions did not share significant systems-level features. Instead, morphometric analyses revealed microcephaly in 1q21.1 and macrocephaly in 15q13.3 deletions, whereas cerebellar volume was specifically reduced in 22q11.2 deletion. In function, 22q11.2 deletion mice showed widespread cortical hypoconnectivity, accompanied by opposing hyperconnectivity in dopaminergic pathways, which was confirmed by graph analysis. 1q21.1 exhibited distinct changes in posterior midbrain morphology and function, especially in periaqueductal gray, whereas 15q13.3 demonstrated alterations in auditory/striatal system. The combination of cortical hypoconnectivity and dopaminergic hyperconnectivity and reduced cerebellum in 22q11.2 deletion mirrors key neurodevelopmental features of schizophrenia, whereas changes in midbrain and auditory/striatal morphology and topology in 1q21.1 and 15q13.3 rather indicate focal processes possibly linked to the emergence of abnormal salience perception and hallucinations. In addition to insights into pathophysiological processes in these microdeletions, our results establish the general point that microdeletions might increase risk for overlapping neuropsychiatric phenotypes through separable neural mechanisms.

Social hierarchies structure groups and confer advantages on high-ranking individuals. In mice, individual position in hierarchies may emerge situationally from current group compositions, or, alternatively, may remain largely stable across groups as an internalized feature. Dominance and subordination are expressed in behaviors like tube competitions or agonistic chasing. The interaction of these behaviors in the shaping of social position in larger male mouse groups remains largely unknown. To address these questions, we developed the NoSeMaze, a semi-naturalistic, open-source, modular platform that enables automated long-term tracking of unperturbed groups. Across more than 4,000 mouse-days, hierarchies derived from incidental competitions in the integrated tube tests were non-despotic, transitive, and stable even when group compositions changed. This stability supports an internalized component of competition-based social rank. Chasing was also stable across contexts. Notably, chasing was concentrated among high-ranking individuals, consistent with ongoing negotiation of social rank among individuals at the upper end of the hierarchy. The link between chasing and social rank strengthened in groups with less well-defined rank structure, where mice rely more on aggressive signaling to assert their position. Chasing and social rank were associated with certain dimensions of simultaneously measured physical and cognitive features. In summary, high-dimensional tracking with the NoSeMaze reveals that social position in mice is multifaceted and shaped by stable dimensions of individual behavior that persist across changing social contexts. The approach thus enables longitudinal modeling of individuality and social position as key resilience factors.

The ability to form stable de novo relationships in complex environments is essential for social functioning and is impaired in severe psychiatric disorders including autism. Yet, the neurobiological basis and cognitive processes enabling the formation of stable bonds in larger groups remain poorly understood, thereby limiting our ability to develop effective therapies. Here, we establish a semi-naturalistic model of clique formation in mouse societies, where individuals are tracked longitudinally from massive video data. Small, stable rich-clubs develop within these mouse social networks. Consistent with human rich-clubs, these cohesive cliques tended to have high social rank and exerted influence on non-members. Interestingly, neither prior rich-club-membership in a different group nor kinship facilitated entry into rich-clubs. Mimicking sparse population genetics, we probed the open question whether a subtle neuro-cognitive phenotype, namely impaired induction of social sensory processing states by cortical oxytocin signaling, disrupts higher-order social bonding in these complex social environments. Despite preserved social motivation, mice with alterations in this oxytocin subsystem failed to join rich-clubs. They approached group members less consistently, and connections from others towards them fluctuated more as well. This reciprocal disorganization highlights how interactional dynamics within social networks can amplify individual-level deficits, consistent with models of emergent properties of social behavior. These findings underscore the role of oxytocin in tuning sensory systems into a social processing state. Its dysfunction affects an individual’s ability to establish stable relationships in complex social networks, with profound implications for social functioning deficits in psychiatric disorders.

Rationale Evidence indicates that ketamine’s rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile. Objectives We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action. Methods The experimental design comprised four parallel groups of rats ( N  = 37), each receiving (S)-Ketamine, CP-101,606, Ro 25-6981 or saline. After compound injection, we acquired resting-state functional magnetic resonance imaging time series. We used graph theoretical approach to calculate brain network properties. Results Ketamine and CP-101,606 diminished the global clustering coefficient and small-worldness index. At the nodal level, all compounds induced increased connectivity of the regions mediating reward and cognitive aspects of emotional processing, such as ventromedial prefrontal cortex, septal nuclei, and nucleus accumbens. The dorsal hippocampus and regions involved in sensory processing and aversion, such as superior and inferior colliculi, exhibited an opposite effect. Conclusions The effects common to ketamine and NR2B-selective compounds were localized to the same brain regions as those reported in depression, but in the opposite direction. The upregulation of the reward circuitry might partially underlie the antidepressant and anti-anhedonic effects of the antagonists and could potentially serve as a translational imaging phenotype for testing putative antidepressants, especially those targeting the NR2B receptor subtype.

Bioreactors have been widely acknowledged as valuable tools to provide a growth environment for engineering tissues and to investigate the effect of physical forces on cells and cell-scaffold constructs. However, evaluation of the bioreactor environment during culture is critical to defining outcomes. In this study, the performance of a hydrostatic force bioreactor was examined by experimental measurements of changes in dissolved oxygen (O 2 ), carbon dioxide (CO 2 ), and pH after mechanical stimulation and the determination of physical forces (pressure and stress) in the bioreactor through mathematical modeling and numerical simulation. To determine the effect of hydrostatic pressure on bone formation, chick femur skeletal cell-seeded hydrogels were subjected to cyclic hydrostatic pressure at 0–270 kPa and 1 Hz for 1 h daily (5 days per week) over a period of 14 days. At the start of mechanical stimulation, dissolved O 2 and CO 2 in the medium increased and the pH of the medium decreased, but remained within human physiological ranges. Changes in physiological parameters (O 2 , CO 2 , and pH) were reversible when medium samples were placed in a standard cell culture incubator. In addition, computational modeling showed that the distribution and magnitude of physical forces depends on the shape and position of the cell-hydrogel constructs in the tissue culture format. Finally, hydrostatic pressure was seen to enhance mineralization of chick femur skeletal cell-seeded hydrogels.