Biology subjects

Hofmann, H. A.

Publications and source records attributed to Hofmann, H. A..

At least 19 recordsLinked to original sources

bioRxiv2026

Social Decision-Making in Response to Competing Stimuli

Animals routinely encounter diverse social stimuli that can be simultaneous and vary in salience, valence and relevance in regard to ongoing behavioral decisions. Understanding how animals weigh such competing information is crucial for revealing the cognitive and neural mechanisms underlying context-dependent social behavior. Here, we investigated how male Astatotilapia burtoni navigate situations in which they must choose between rival males, potential mates, or both socially relevant cues. We first quantified focal male engagement toward stimulus types and found that males prioritized stimuli based on identity, context, and inferred threat level. We then examined the underlying neural correlates of these decisions in the preoptic area (POA) and area Dm (the putative teleost homolog of the basolateral amygdala (area Dm), two key nodes of the social decision-making network (SDMN). Using phosphorylated ribosomal protein S6 (pS6) as a marker of neural activity and tyrosine hydroxylase (TH) to identify dopaminergic cell populations, we found that overall activity of these brain regions as well as the activity of dopaminergic cell populations did not differ between the different social stimulus treatments. Our results reveal how animals navigate complex environments involving multiple social cues and highlight the behavioral and neural mechanisms supporting stimulus prioritization.

animal behavior and cognition↗

bioRxiv2026

Preoptic transcriptomes during courtship reveal the molecular basis of behavioral coordination in a highly social cichlid

Human and non-human animals often coordinate their behavior, a phenomenon thought to strengthen relationships by enabling sequential assessment of an interaction partners quality as a mate or rival, a process that directly affects evolutionary fitness. There is increasing evidence that behavioral coordination is reflected by synchronized neural activity of the on interacting partners, though few studies have examined synchronization at the level of gene expression. Here, we use Burtons Mouthbrooder cichlid, Astatotilapia burtoni, to examine how neural transcriptomes are synchronized while male-female pairs engaged in variable amounts of reproductive behavior. A. burtoni females naturally display highly coordinated reproductive behavior with a male partner only directly prior to spawning, yet this behavior can be experimentally induced with exogenous prostaglandin F2 alpha (PGF2a), which also acts by releasing pheromones to promote male courtship behavior. We quantified reproductive behavior and circulating sex steroid hormones of PGF2a-treated pairs. We then used transcriptome analysis of the preoptic area - a key node in the regulation of reproductive behavior across vertebrates - and identified gene co-expression modules that showed sex-specific activity in modulating reproductive behavior. Our results, which implement a novel approach to measure transcriptome synchronization, demonstrate a remarkable degree of male-female POA transcriptome synchronization that depends largely on the reproductive responsiveness of the female, mirroring how natural reproduction is driven by female behavior. Together, our work advances our understanding of the molecular mechanisms by which interacting individuals align their actions and how they experience social interaction.

animal behavior and cognition↗

bioRxiv2026

Context and Identity Cues Mediate Individual Recognition in a Highly Social Cichlid Fish

Social animals must identify, evaluate, and appropriately respond to other individuals, often relying on multiple sources of information to guide context-dependent behavior. While individual recognition is thought to be widespread and critical for many social interactions (e.g. territoriality, dominance hierarchies), convincing demonstrations across animals beyond class-level recognition remain rare. Further, the cues animals use to recognize individuals remains poorly understood, especially in natural environments where they are exposed to numerous cues which may require cue integration. Here, we examine how socially dominant males of the African cichlid fish, Astatotilapia burtoni, use individual recognition to modulate aggression and whether this process depends on the spatial context. Using naturalistic experimental setups, we exposed males to familiar and unfamiliar neighbors while systematically manipulating spatial location and presenting a neighbor either singly or simultaneously to simulate competing social cues. Additionally, we measured circulating testosterone to assess endocrine correlates of recognition and aggression. We found that focal males habituated to familiar neighbors only when they remained in a consistent territorial location, demonstrating that spatial context is important for recognition. Further, when familiar and unfamiliar neighbors were presented simultaneously, males preferentially aggressed toward unfamiliar rival and adjust their aggressive response to the perceived threat of their neighbors, indicating that identity-based threat assessment is maintained under competing social demands. Together, our results show that recognition is a flexible, multi-faceted process that depends on the integration of identity and contextual information to guide territorial decision-making under dynamic social conditions.

animal behavior and cognition↗

bioRxiv2026

trAIt: Species-by-Trait Data Retrieval using Large Language Models

Biological research often requires information about species traits. Manual literature collation can be time-consuming and miss parts of the literature. To address this gap, we developed trAIt, a publicly available software for the retrieval of characteristics of species from scientific literature catalogued in the Europe PubMed Central (PubMed) database. trAIt provides a graphical user interface (GUI) in which users specify species and characteristics of interest. Leveraging a large language model (LLM), trAIt retrieves relevant papers, combines their content through a consensus-based summarization model, and outputs a species-by-characteristic table. For a case study involving frog species, trAIt recovered 47.1% of trait-species combinations in 2.75 hours, while an expert curator independently recovered 62.4% over months. The consensus-based summarization substantially aids accuracy compared to single-source extraction. Across three case studies of vertebrate taxa, an expert confirmed the accuracy of 70.9% of trait-species entries recovered by trAIt. We observed considerable variation across taxa in trAIts accuracy, which is possibly due to heterogeneity in open-access literature availability and inconsistencies in species and trait terminology. In sum, our analysis suggests that LLM-based tools can accelerate biological data synthesis but should be used to support domain experts research, rather than replace their judgment.

bioinformatics↗

bioRxiv2026

Single-Nucleus Transcriptomics of the Mouse Medial Preoptic Area Reveals Sex-Dependent Molecular Signatures of Social Dominance

Social dominance hierarchies are a common form of social organization across animal species. We have previously shown that both male and female CD-1 mice form highly linear dominance hierarchies. In mice and other vertebrates, the medial preoptic area (mPOA) is a key hypothalamic sub-region regulating aggressive and defensive behaviors that support hierarchical social structures, but the transcriptional mechanisms in mPOA neurons underlying dominance behaviors and the influence of sex on these neuron populations in the context of social dominance hierarchies remain largely unresolved. Using single-nucleus RNA sequencing (snRNA-seq) to profile mPOA neurons from dominant and subordinate mice, we identified highly consistent social status-dependent changes in the transcriptomes of neuronal nuclei expressing neuropeptide transcripts. Oxytocin expression was remarkably widespread across mPOA neurons, and we found it to be the primary driver of group differences in neuropeptide co-expression networks. Overall, dominant males and females exhibited markedly decreased expression of oxytocin and vasopressin and had a lower proportion of neurons co-expressing multiple neuropeptide transcripts compared to subordinate individuals. In contrast, subordinates displayed widespread reorganization of the transcriptomic neuropeptidome and strikingly enhanced coupling of neuropeptide expression in mPOA neurons. Despite the strong pattern of concordant gene expression in dominant and subordinate individuals, the number of genes that were differentially expressed by status was substantially reduced in males compared to females. In sum, these results demonstrate that maintenance of social status dynamically reconfigures hypothalamic transcriptomic neuropeptidome in a sex-dependent manner and establishes how social status is encoded at a single-cell resolution.

neuroscience↗

bioRxiv2025

Social Processing in the Amygdala: Single-Nucleus RNA-Sequencing Reveals Distinct Neuronal Responses to Dominant and Subordinate Cues

The amygdala serves as a critical neural hub for interpreting social cues, with its distinct subregions and diverse neuronal populations playing specialized roles in processing these signals. This study employs single-nucleus RNA sequencing (snRNA-seq) to characterize the amygdalas neuronal responses to olfactory cues associated with social dominance, uncovering distinct activation patterns within glutamatergic and GABAergic populations. We find that a glutamatergic cluster, characterized by expression patterns closely aligned with glutamatergic Slc17a7 (VGLUT1) medial amygdala (MeA) neurons, preferentially responds to dominant cues. In contrast, a larger glutamatergic Slc17a6 (VGLUT2) cluster associated with neurons of the MeA, as well as cortical and basomedial amygdala, exhibits a heightened response to subordinate cues, underscoring the MeA regions role in processing social olfactory information. Additionally, a glutamatergic cluster resembling dorsal endopririform (EPd) neurons responded more to dominant stimuli, supporting the EPds role in olfactory perception. We also identified a GABAergic cluster with elevated dopamine receptor 2 (Drd2) expression that predominantly responds to dominant cues, consistent with this receptors known role in mediating threat responses. Through gene co-expression network analysis, we linked gene expression within neuronal clusters to specific biological processes. These findings reveal distinct neuronal and molecular mechanisms underlying social processing, particularly in response to dominant and subordinate olfactory signals, thus enhancing our understanding of the neural substrates of social behavior.

neuroscience↗

bioRxiv2025

Persistently increased expression of PKMzeta and unbiased gene expression profiles identify hippocampal molecular traces of a long-term active place avoidance memory and 'shadow' proteins

Long-term memory formation transiently activates Ca2+-calmodulin kinase II and atypical protein kinase C isoform iota/lambda, whereas persistent activation of the other atypical PKC, protein kinase M zeta (PKM{zeta}), together with its interacting partner, the scaffolding-protein KIBRA (Wwc1), are necessary for maintaining potentiated synapses and memory. Here, we use immediate-early gene (IEG) Arc activation during active place avoidance memory expression to tag memory-activated neurons with EYFP-ChR2. PKM{zeta} immunohistochemistry identified which hippocampal synaptic pathways are persistently altered. EYFP-PKM{zeta} colocalization persistently increases in the hippocampal trisynaptic pathway (dentate gyrus [DG][->]CA3[->]CA1) tracing a one-month-old PKM{zeta} engram. DG, CA3, and CA1 transcriptional profiling identifies that memory persistence correlates with upregulated immediate-early-genes Arc, Fos, and NPas4 in DG, but not with PKM{zeta} or most genes known to be crucial for LTP and memory. This rules out strong memory-related transcriptional regulation, but not regulation of mRNA translation or altered stability of "shadow proteins" like PKM{zeta} that, despite being crucial for memory maintenance, evade detection by unbiased transcriptome profiling. In contrast, our method Correlation Signal Co-cluster Reduction (C-SCoRe) incorporates weak linear and non-linear gene correlations and highlights network interaction changes predicting memory, and related IEG and Prkcz/Wwc1 expression. Manifold transcriptional relationships can reveal shadow molecular components of long-term memory.

neuroscience↗

bioRxiv2024

Single-nuclei transcriptomes in the hypothalamus and POA of a highly social cichlid

Complex behavioral phenotypes, such as social status, emerge from the genome across biological levels, with many of the fundamental neural mechanisms shared across vertebrates. While various aspects of the brain have been implicated in modulating social behavior, critical regulators include cells of the preoptic area (POA) and hypothalamus, which by applying cellular- resolution transcriptomic approaches allows for greater exploration of cellular dynamics in these cells. Yet, how complex gene networks function between and within cell types to regulate complex social behavior is still poorly understood. Importantly, when considering functionally relevant neuronal classes of genes such as neuropeptides, understanding the inherent complexity that emerges from the interaction of these genes in the transcriptomic neuropeptidome can provide unique insight into how social behavior is regulated. Here, we used single-nucleus RNA-sequencing in the hypothalamus and POA of a highly social cichlid fish, Astatotilapia burtoni, to understand the effect that social status has on cellular-level transcriptomic profiles. Males of this species are well known for their highly plastic phenotypes related to social status, which allows for a hypothesis-driven approach. We demonstrate how social status manifests in changes of gene co-expression networks across neuronal populations and highlight transcriptomic signatures of social dominance when targeting known functional differences among AVP neuronal cell types. We implement a novel approach to relate how differences in social state translate to the integration of the transcriptomic neuropeptidome. Taken together, this research provides insights into how gene expression networks that modulate social behavior, including neuropeptide networks, function at the cellular level. Significance StatementHere, we used single-nucleus RNA-seq in the hypothalamus and POA of Astatotilapia burtoni to understand the effect that social status has on cellular gene expression. We demonstrate how social status manifests, from changes in broader neuronal gene networks to targeted changes between known socially-relevant neurons. For the first time, we assess the entirety of the transcriptomic neuropeptidome to understand the interaction of neuropeptide gene networks with social dominance. These findings provide a valuable resource for future functional work and an analytical framework for comparative studies on the evolution of the neural mechanisms of social behavior. Insights into the transcriptomic networks that modulate social status, specifically with neuropeptides, aid in our understanding of the complexity inherent in social behavior.

neuroscience↗

bioRxiv2024

Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies

Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies. We show that mice of all social ranks rapidly establish new stable social hierarchies when placed in novel social groups with animals of equivalent social status. Seventy minutes following social hierarchy formation, previously socially dominant animals exhibit higher increases in plasma corticosterone and vastly greater transcriptional changes in the medial amygdala (MeA), which is central to the regulation of social behavior, compared to previously subordinate animals. Specifically, social descent is associated with reductions in MeA expression of myelination and oligodendrocyte differentiation genes. Maintaining high social status is associated with high expression of genes related to cholinergic signaling in the MeA. Conversely, social ascent is related to relatively few unique rapid changes in the MeA. We also identify novel genes associated with social transition that show common changes in expression when animals undergo either social descent or social ascent compared to maintaining their status. Two genes, Myosin binding protein C1 (Mybpc1) and -Crystallin (Crym), associated with vasoactive intestinal polypeptide (VIP) and thyroid hormone pathways respectively, are highly upregulated in socially transitioning individuals. Further, increases in genes associated with synaptic plasticity, excitatory glutamatergic signaling and learning and memory pathways were observed in transitioning animals suggesting that adaptations in these processes may support rapid social status changes. Author SummaryWe investigate how male CD-1 mice behaviorally, physiologically, and molecularly respond to changes in their social hierarchies. We found that mice rapidly reform social hierarchies when placed into novel social groups. Formerly dominant mice experience the greatest increase in stress hormone levels and the largest shifts in gene expression in the medial amygdala, a brain region crucial for regulating social behavior. Specifically, we observed reduced expression of genes related to myelin production and maintenance as well as cholinergic functioning in formerly dominant males who socially descended. In contrast, formerly subordinate males who socially ascended displayed fewer genomic changes. Moreover, we identified a set of genes that change expression when animals transition their social status regardless of whether they rise or fall in rank. These social transition genes provide new insights into the biological mechanisms underpinning social plasticity. Our findings demonstrate the distinct molecular mechanisms that are shared between socially ascending versus descending mice, as well as those that are unique to each type of social transition.

neuroscience↗

bioRxiv2024

Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells

Contextual fear conditioning has been shown to activate a set of "fear ensemble" cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells - the "extinction ensemble." Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.

neuroscience↗

bioRxiv2023

Mate choice in the brain: Species differ in how male traits 'turn on' gene expression in female brains

Mate choice plays a fundamental role in speciation, yet we know little about the molecular mechanisms that underpin this crucial decision-making process. Female stickleback fish differentially adapted to limnetic and benthic habitats and considered members of reproductively isolated species use different male traits to evaluate prospective partners and reject heterospecific males. Here, we integrate behavioral data from a mate choice experiment involving benthic and limnetic fish with gene expression data from the brains of females making these mate choice decisions. We find substantial gene expression variation between limnetic and benthic species, regardless of behavioral context, suggesting general divergence in gene expression patterns in female brains, in accordance with their genetic differentiation. Intriguingly, female gene co-expression modules covary with male display traits but in opposing directions for sympatric populations of the two species, suggesting male displays elicit a genomic response that reflects known differences in female preferences which serve to isolate the species. Furthermore, our analysis confirms the role of numerous candidate genes previously implicated in female mate choice decision-making in other teleost species, suggesting that these cognitive molecular processes are, in part, evolutionarily conserved. Taken together, our study adds important new insights to our understanding of the molecular processes underlying female decision-making that maintain isolation between diverging species.

animal behavior and cognition↗

bioRxiv2021

Morpholino-mediated knockdown of the brain mineralocorticoid receptor affects glucocorticoid signaling and neuroplasticity in wild ocellated wrasse (Symphodus ocellatus)

Uncovering the genetic, physiological, and developmental mechanisms underlying phenotypic variation is necessary for understanding how genetic and genomic variation shape phenotypic variation and for discovering possible targets of selection. Although the neural and endocrine mechanisms underlying social behavior are evolutionarily ancient, we lack an understanding of the proximate causes and evolutionary consequences of variation in these mechanisms. Here, we examine in the natural environment the behavioral, neuromolecular, and fitness consequences of a morpholino-mediated knockdown of the mineralocorticoid receptor (MR) in the brain of nesting males of the ocellated wrasse, Symphodus ocellatus, a species with male alternative reproductive tactics. Even though MR knockdown did not significantly change male behavior directly, this experimental manipulation strongly altered glucocorticoid signaling and neuroplasticity in the preoptic area, the putative hippocampus homolog, and the putative basolateral amygdala homolog. We also found that individual variation in stress axis gene expression and neuroplasticity is strongly associated with variation in male behavior and fitness-related traits. The brain region-specific effects of MR knockdown on phenotypic integration in the wild reported here suggest specific neuroendocrine and neuroplasticity pathways that may be targets of selection.

animal behavior and cognition↗

bioRxiv2021

Sex differences in parental response to offspring begging are associated with pair bond strength across birds

Mothers, fathers, and offspring regularly clash over how much care offspring receive. Offspring beg to solicit for more resources--but how much begging is rewarded can depend on who is listening. While both parents benefit from provisioning offspring, each would benefit from their partner shouldering more of the burden of care, leading to sexual conflict. Additionally, if the costs and benefits of provisioning differ by sex, parent-offspring conflict should vary by sex. How these evolutionary conflicts influence sex differences in parent-offspring communication is unknown. To determine whether the sexes differ in their response to offspring signals, we conducted a meta-analysis on 30 bird species, comparing responsiveness to social and physiological traits affecting conflict. We found that a species typical pair bond strength predicts whether males or females respond more to offspring begging. In species with stable and/or monogamous bonds, and thus lower sexual and paternal-offspring conflict, males provisioning effort is more strongly correlated with offspring begging than females. The opposite holds for species with weak pair bonds: females respond more to begging, perhaps compensating for males lower responsiveness. These results demonstrate that sex differences in parental care can arise via sex differences in parent-offspring communication, driven by evolutionary conflicts.

animal behavior and cognition↗

bioRxiv2021

Differential neural activity patterns mediate learning across contexts in a social cichlid fish

Learning and decision-making are greatly influenced by the social context surrounding individuals. When navigating a complex social world, individuals must quickly ascertain where to gain important resources and which group members are useful sources of such information. Such dynamic behavioral processes require neural mechanisms that are flexible across contexts. Here we examined how the social context influences the learning response during a visual cue discrimination task and the neural activity patterns that underlie acquisition of this novel information. Using the cichlid fish, Astatotilapia burtoni, we show that learning of the task is faster in social groups than in a non-social context. We quantified the expression of Fos, an immediate-early gene, across candidate brain regions known to play a role in social behavior and learning, such as the putative teleost homologues of the mammalian hippocampus, basolateral amygdala, and medial amygdala/BNST complex. We found that neural activity patterns differ between social and non-social contexts. Our results suggest that while the same brain regions may be involved in the learning of a discrimination task independent of social context, activity in each region encodes specific aspects of the task based on context.

neuroscience↗

bioRxiv2020

Prenatal exposure to EDCs dis-integrates and reconstitutes neuromolecular-behavioral relationships in adult rats

AO_SCPLOWBSTRACTC_SCPLOWExposure 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.

neuroscience↗

bioRxiv2020

Equal performance but distinct behaviors: Astatotilapia burtoni sex differences in a novel object recognition task and spatial maze

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.

animal behavior and cognition↗

bioRxiv2020

Transcriptome analysis of hippocampal subfields identifies gene expression profiles associated with long-term active place avoidance memory

The hippocampus plays a critical role in storing and retrieving spatial information. By targeting the dorsal hippocampus and manipulating specific "candidate" molecules using pharmacological and genetic manipulations, we have previously discovered that long-term active place avoidance memory requires transient activation of particular molecules in dorsal hippocampus. These molecules include amongst others, the persistent kinases Ca-calmodulin kinase II (CaMKII) and the atypical protein kinase C isoform PKC{iota} /{lambda} for acquisition of the conditioned behavior, whereas persistent activation of the other atypical PKC, protein kinase M zeta (PKM{zeta}) 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 Ammons 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.

neuroscience↗

bioRxiv2019

Comparative transcriptomics reveal distinct patterns of gene expression conservation through vertebrate embryogenesis

Despite lifes 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.

evolutionary biology↗