typical protein kinase C isoform PKC ι/λ for acquisition of the conditioned behavior, whereas persistent activation of the other atypical PKC, protein kinase M zeta (PKMζ) is necessary for maintaining the memory for at least a month. It nonetheless remains unclear what other molecules and their interactions maintain active place avoidance long-term memory, and the candidate molecule approach is both impractical and inadequate to identify new candidates since there are so many to survey. Here we use a complementary approach to identify candidates by transcriptional profiling of hippocampus subregions after formation of the long-term active place avoidance memory. Interestingly, 24-h after conditioning and soon after expressing memory retention, immediate early genes were upregulated in the dentate gyrus but not Ammon’s horn of the memory expressing group. In addition to determining what genes are differentially regulated during memory maintenance, we performed an integrative, unbiased survey of the genes with expression levels that covary with behavioral measures of active place avoidance memory persistence. Gene Ontology analysis of the most differentially expressed genes shows that active place avoidance memory is associated with activation of transcription and synaptic differentiation in dentate gyrus but not CA3 or CA1, whereas hypothesis-driven candidate molecule analyses identified insignificant changes in the expression of many LTP-associated molecules in the various hippocampal subfields, nor did they covary with active place avoidance memory expression, ruling out strong transcriptional regulation but not translational regulation, which was not investigated. These findings and the data set establish an unbiased resource to screen for molecules and evaluate hypotheses for the molecular components of a hippocampus-dependent, long-term active place avoidance memory.
Understanding animal decision-making involves simultaneously dissecting and reconstructing processes across levels of biological organization, such as behavior, physiology, and brain function, as well as considering the environment in which decisions are made. Over the past few decades, foundational breakthroughs originating from a variety of model systems and disciplines have painted an increasingly comprehensive picture of how individuals sense information, process it, and subsequently modify behavior or states. Still, our understanding of decision-making in social contexts is far from complete and requires integrating novel approaches and perspectives. The fields of social neuroscience and cognitive ecology have approached social decision-making from orthogonal perspectives. The integration of these perspectives (and fields) is critical in developing comprehensive and testable theories of the brain.
Background: There is a growing literature from both epidemiologic and experimental animal studies suggesting that exposure to air pollution can lead to neurodevelopmental and neuropsychiatric disorders. Here, we suggest that efects of air pollutant exposure on the brain may be even broader, with the potential to afect social decision-making in general. Methods: We discuss how the neurobiological substrates of social behavior are vulnerable to air pollution, then briefy present studies that examine the efects of air pollutant exposure on social behavior-related outcomes.
Results: Few experimental studies have investigated the efects of air pollution on social behavior and those that have focus on standard laboratory tests in rodent model systems. Nonetheless, there is sufcient evidence to support a critical need for more research. Conclusion: For future research, we suggest a comparative approach that utilizes diverse model systems to probe the efects of air pollution on a wider range of social behaviors, brain regions, and neurochemical pathways. Keywords: Air pollution, Social behavior, Particulate matter, Ozone, Social decision-making network, Dopamine, Sex steroids, Inhalation, Hazardous air pollutants
Background Mood disorders represent a major cause of morbidity and mortality worldwide but the brain-related molecular pathophysiology in mood disorders remains largely undefined.
Methods Because the anterior insula is reduced in volume in patients with mood disorders, RNA was extracted from postmortem mood disorder samples and compared with unaffected control samples for RNA-sequencing identification of differentially expressed genes (DEGs) in a) bipolar disorder (BD; n=37) versus (vs.) controls (n=33), and b) major depressive disorder (MDD n=30) vs controls, and c) low vs. high Axis-I comorbidity (a measure of cumulative psychiatric disease burden). Given the regulatory role of transcription factors (TFs) in gene expression via specific-DNA-binding domains (motifs), we used JASPAR TF binding database to identify TF-motifs.
Results We found that DEGs in BD vs. controls, MDD vs. controls, and high vs. low Axis-I comorbidity were associated with TF-motifs that are known to regulate expression of toll-like receptor genes, cellular homeostatic-control genes, and genes involved in embryonic, cellular/organ and brain development.
DiscussionRobust imaging-guided transcriptomics (i.e., using meta-analytic imaging results to guide independent post-mortem dissection for RNA-sequencing) was applied by targeting the gray matter volume reduction in the anterior insula in mood disorders, to guide independent postmortem identification of TF motifs regulating DEG. TF motifs were identified for immune, cellular, embryonic and neurodevelopmental processes.
Conclusion Our findings of TF-motifs that regulate the expression of immune, cellular homeostatic-control, and developmental genes provides novel information about the hierarchical relationship between gene regulatory networks, the TFs that control them, and proximate underlying neuroanatomical phenotypes in mood disorders.
Exposure to endocrine-disrupting chemicals (EDCs) is ubiquitous in all species, including humans. Previous studies have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs [polychlorinated biphenyls (PCB), an industrial chemical mixture; vinclozolin (VIN), a fungicide], or vehicle. In adulthood, a sociosexual preference test (choice between hormone-primed and hormone-depleted opposite-sex rats) was administered. We profiled gene expression of in three brain regions involved in these behaviors [preoptic area (POA), medial amygdala (MeA), ventromedial nucleus (VMN)]. Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region (POA, MeA, VMN) had unique sets of genes altered in a sex- and EDC-specific manner. Sexually dimorphic gene expression disruption was particularly prominent for gene modules pertaining to sex steroid hormones and nonapeptides in the MeA. EDC exposure also changed the relationships between gene expression and behavior in the mate preference test, a pattern we refer to as dis-integration and reconstitution. These findings underscore the profound effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of mate preference behavior after prenatal exposure to EDCs.
Sex differences in behavior and cognition can be driven by differential selection pressures from the environment and in the underlying neuromolecular mechanisms of decision-making. The highly social cichlid fish Astatotilapia burtoni exhibits dynamic and complex social hierarchies, yet explicit cognitive testing (outside of social contexts) and investigations of sex differences in cognition have yet to be fully explored. Here we assessed male and female A. burtoni in two cognitive tasks: a novel object recognition task and a spatial task. We hypothesized that males outperform females in a spatial learning task and exhibit more neophilic/exploratory behavior in across both tasks. In the present study we find that both sexes prefer the familiar object in a novel object recognition task, but the time at which they exhibit this preference differs between the sexes. Females more frequently learned the spatial task, exhibiting longer decision latencies and quicker error correction, suggesting a potential speed-accuracy tradeoff.
Furthermore, the sexes differ in space use in both tasks and in a principal component analysis of the spatial task. A model selection analysis finds that preference, approach, and interaction duration in the novel object recognition task that reach a threshold of importance averaged across all models. This work highlights the need to explicitly test for sex differences in cognition to better understand how individuals navigate dynamic social environments.
Despite life’s diversity, studies of variation across animals often remind us of our shared evolutionary past. Abundant genome sequencing over the last ~25 years reveals remarkable conservation of genes and recent analyses of gene regulatory networks illustrate that not only genes but entire pathways are conserved, reused, and elaborated in the evolution of diversity. Predating these discoveries, 19th-century embryologists observed that though morphology at birth varies tremendously, certain stages of embryogenesis appear remarkably similar across vertebrates. Specifically, while early and late stages are variable across species, anatomy of mid-stages embryos (the ‘phylotypic’ stage) is conserved. This model of vertebrate development and diversification has found mixed support in recent analyses comparing gene expression across species possibly owing to differences across studies in species, embryonic stages, and gene sets compared. Here we perform a comparative analysis using 186 microarray and RNA-seq expression data sets covering embryogenesis in six vertebrate species spanning ~420 million years of evolution. We use an unbiased clustering approach to group stages of embryogenesis by transcriptomic similarity and ask whether gene expression similarity of clustered embryonic stages deviates from the null hypothesis of no relationship between timing and diversification. We use a phylogenetic comparative approach to characterize expression conservation pattern (i.e., early conservation, hourglass, inverse hourglass, late conservation, or no relationship) of each gene at each evolutionary node. Across vertebrates, we find an enrichment of genes exhibiting early conservation, hourglass, late conservation patterns and a large depletion of gene exhibiting no distinguishable pattern of conservation in both microarray and RNA-seq data sets. Enrichment of genes showing patterned conservation through embryogenesis indicates diversification of embryogenesis may be temporally constrained. However, the circumstances (e.g., gene groups, evolutionary nodes, species) under which each pattern emerges remain unknown and require both broad evolutionary sampling and systematic examination of embryogenesis across species.
Female mate choice is a dynamic process that allows individuals to selectively mate with those of the opposite sex that display a preferred set of traits. Because in many species males compete with each other for fertilization opportunities, female mate choice can be a powerful agent of sexual selection, often resulting in highly conspicuous traits in males. Although the evolutionary causes and consequences of the ornamentation and behaviors displayed by males to attract mates have been well studied, embarrassingly little is known about the proximate neural mechanisms through which female choice occurs. In vertebrates, female mate choice is inherently a social behavior, and although much remains to be discovered about this process, recent evidence suggests the neural substrates and circuits underlying other fundamental social behaviors (such as pair bonding, aggression and parental care) are likely similarly recruited during mate choice. Notably, female mate choice is not static, as social and ecological environments can shape the brain and, consequently, behavior in specific ways. In this Review, we discuss how social and/or ecological influences mediate female choice and how this occurs within the brain. We then discuss our current understanding of the neural substrates underlying female mate choice, with a specific focus on those that also play a role in regulating other social behaviors. Finally, we propose several promising avenues for future research by highlighting novel model systems and new methodological approaches, which together will transform our understanding of the causes and consequences of female mate choice.