Biology subjects

Hindmarsh Sten, T.

Publications and source records attributed to Hindmarsh Sten, T..

6 recordsLinked to original sources

bioRxiv2026

Hypothalamic Cell Type Evolution across Vertebrates

The hypothalamus regulates vital functions and is highly conserved among vertebrates occupying diverse niches, but little is known about the evolution of its cell types. Using comparative single-cell transcriptomics across major vertebrate classes, we identified deeply conserved and clade-specific cell types. While homologous cell types express conserved transcription factors and neuropeptides, their regulatory linkages are often rewired across evolution. The paraventricular nucleus largely retains its neuropeptide expression and responds to dehydration with fine cellular resolution from amphibians to mammals, whereas lamina terminalis neurons are specific to terrestrial vertebrates and exhibit gene expression divergence in cell types activated by dehydration and heat. We propose that a conserved set of keystone cell types sustain essential functions across vertebrates, while flexible gene regulatory programs alongside numerous clade-specific cell types offer evolutionary fluidity.

evolutionary biology↗

bioRxiv2026

Projectomic Organization of the Serotonin System of the Mouse Brain

The serotonin system innervates nearly the entire brain to support diverse functions, and its dysfunction is implicated in multiple psychiatric disorders. Although recent studies suggested that this anatomically diffuse system supports differentiated rather than uniform modulation, its overall organization is unclear. Here, using systematic whole-brain axon tracing and integrated analyses, we show that the serotonin projectome is organized by functional relatedness rather than physical proximity of its targets. Dorsal and median raphe serotonin neurons partition into five projectomic groups, each preferentially innervating the hippocampus, basal ganglia, cortex, medial interbrain, or brainstem/lateral thalamus, with within-group structure ranging from discrete subgroups to continuous variation. Spatial transcriptomic analyses reveal that each projectomic group corresponds to a distinct combination of transcriptomic clusters, with transcriptome and somatic position jointly predicting projectomic identity. Projection-specific serotonin depletion produces dissociable behavioral phenotypes. Together, projectomic identity emerges as a central axis linking axon collateralization, molecular diversity, and behavioral function.

neuroscience↗

bioRxiv2024

Social state gates vision using three circuit mechanisms in Drosophila

Animals are often bombarded with visual information and must prioritize specific visual features based on their current needs. The neuronal circuits that detect and relay visual features have been well-studied. Yet, much less is known about how an animal adjusts its visual attention as its goals or environmental conditions change. During social behaviors, flies need to focus on nearby flies. Here, we study how the flow of visual information is altered when female Drosophila enter an aggressive state. From the connectome, we identified three state-dependent circuit motifs poised to selectively amplify the response of an aggressive female to fly-sized visual objects: convergence of excitatory inputs from neurons conveying select visual features and internal state; dendritic disinhibition of select visual feature detectors; and a switch that toggles between two visual feature detectors. Using cell-type-specific genetic tools, together with behavioral and neurophysiological analyses, we show that each of these circuit motifs function during female aggression. We reveal that features of this same switch operate in males during courtship pursuit, suggesting that disparate social behaviors may share circuit mechanisms. Our work provides a compelling example of using the connectome to infer circuit mechanisms that underlie dynamic processing of sensory signals.

neuroscience↗

bioRxiv2023

Male-male interactions shape mate selection in Drosophila

Males of many species have evolved behavioral traits to both attract females and repel rivals. Here, we explore mate selection in Drosophila from both the male and female perspective to shed light on how these key components of sexual selection -- female choice and male-male competition -- work in concert to guide reproductive strategies. We find that male flies fend off competing suitors by interleaving their courtship of a female with aggressive wing flicks, which both repel competitors and generate a song that obscures the females auditory perception of other potential mates. Two higher-order circuit nodes - P1a and pC1x neurons - are coordinately recruited to allow males to flexibly interleave these agonistic actions with courtship displays, assuring they persistently pursue females until their rival falters. Together, our results suggest that female mating decisions are shaped by male-male interactions, underscoring how a males ability to subvert his rivals is central to his reproductive success.

neuroscience↗

bioRxiv2020

An arousal gated visual circuit controls pursuit during Drosophila courtship

Long-lasting internal states, like hunger, aggression, and sexual arousal, pattern ongoing behavior by defining how the sensory world is translated to specific actions that subserve the needs of an animal. Yet how enduring internal states shape sensory processing or behavior has remained unclear. In Drosophila, male flies will perform a lengthy and elaborate courtship ritual, triggered by activation of sexually-dimorphic P1 neurons, in which they faithfully follow and sing to a female. Here, by recording from males as they actively court a fictive female in a virtual environment, we gain insight into how the salience of female visual cues is transformed by a males internal arousal state to give rise to persistent courtship pursuit. We reveal that the gain of LCt0a visual projection neurons is strongly increased during courtship, enhancing their sensitivity to moving targets. A simple network model based on the LCt0a circuit accurately predicts a males tracking of a female over hundreds of seconds, underscoring that LCt0a visual signals, once released by P1-mediated arousal, become coupled to motor pathways to deterministically control his visual pursuit. Furthermore, we find that P1 neuron activity correlates with fluctuations in the intensity of a males pursuit, and that their acute activation is sufficient to boost the gain of the LCt0 pathways. Together, these results reveal how alterations in a males internal arousal state can dynamically modulate the propagation of visual signals through a high-fidelity visuomotor circuit to guide his moment-to-moment performance of courtship.

neuroscience↗

bioRxiv2018

Dissociating task acquisition from expression during learning reveals latent knowledge

Performance on cognitive tasks during learning is used to measure intelligence, yet it remains controversial since such testing is susceptible to contextual factors. To what extent does performance during learning depend on the testing context, rather than underlying knowledge? We trained mice, rats and ferrets on a range of tasks to examine how testing context impacts the acquisition of knowledge versus its expression. We interleaved reinforced trials with \"probe\" trials in which we omitted reinforcement. Across tasks, each animal species performed remarkably better in probe trials during learning and inter-animal variability was strikingly reduced. Reinforcement feedback is thus critical for learning-related plasticity but, paradoxically, masks the expression of underlying knowledge. We capture these results with a network model in which learning occurs during reinforced trials while context modulates only the read-out parameters. Probing learning by omitting reinforcement thus uncovers latent knowledge and identifies context--not \"smartness\"--as the major source of individual variability.\n\nHIGHLIGHTSO_LIKnowledge acquisition and expression can be segregated by the introduction of non-reinforced probe trials across a variety of animal species and behavioral tasks.\nC_LIO_LIAnimals learn much faster and in a more stereotyped way in non-reinforced probe trials than their performance in the presence of reinforcement suggests.\nC_LIO_LIUnderperformance and variability in performance arise from sensitivity to the behavioral testing context, not acquisition of sensorimotor associations.\nC_LIO_LIA circuit model accounts for context-dependent performance by modulating the integration of sensorimotor associations.\nC_LI\n\neTOCKuchibhotla et al. show the acquisition and expression of knowledge can be behaviorally dissociated in mice, rats, and ferrets across a variety of sensorimotor tasks. Across animals, variability in performance arises from the testing context, not underlying aptitude.

neuroscience↗