Biology subjects

Sternson, S. M.

Publications and source records attributed to Sternson, S. M..

5 recordsLinked to original sources

bioRxiv2026

Whole-Brain Co-Mapping of Gene Expression and NeuronalActivity at Cellular Resolution in Behaving Zebrafish

The brains capabilities rely on both the molecular properties of individual cells and their interactions across brain-wide networks. However, relating gene expression to activity in individual neurons across the entire brain remains elusive. Here we developed an experimental-computational platform, WARP, for whole-brain imaging of neuronal activity during behavior, expansion-assisted spatial transcriptomics, and cellular-level registration of these two modalities. Through joint analysis of whole-brain neuronal activity during multiple behaviors, cellular gene expression, and anatomy, we identified functions of molecularly defined populations--including luminance coding in a cckb-pou4f2 midbrain population and task-structured activity in pvalb7-eomesa hippocampal-like neurons--and defined over 2,000 other function-gene-anatomy subpopulations. Analysis of this unprecedented multimodal dataset also revealed that most gene-matched neurons showed stronger activity correlations, highlighting a brain-wide role for gene expression in functional organization. WARP establishes a foundational platform and open-access dataset for cross-experiment discovery, high-throughput function-to-gene mapping, unification of cell biology and systems neuroscience, and scalable circuit modeling at the whole-brain scale.

neuroscience↗

bioRxiv2024

Modulation of calcium signaling on demand to decipher the molecular mechanisms of primary aldosteronism

Primary aldosteronism (PA) is the most common form of secondary hypertension. Major advances have been made in our understanding of PA with the identification of germline and somatic mutations in ion pumps and channels. These mutations lead to the activation of calcium signalling, the major trigger of aldosterone biosynthesis. To elucidate the molecular mechanisms underlying the development of PA, we established an adrenocortical cell model in which we can modulate sodium entry into the cells "on demand" leading to calcium signalling activation. These cells recapitulated the major features of KCNJ5 mutations, the most frequent genetic alteration identified in Aldosterone-Producing-Adenoma. Activation of calcium signalling was associated with increased aldosterone biosynthesis and decreased cell proliferation. RNA sequencing and steroidome analyses revealed unique profiles associated with Na+ entry. Altogether, this work offers valuable insights into the role of sodium-induced calcium signalling in PA development and paves the way for developing new therapeutic strategies.

physiology↗

bioRxiv2021

Expansion-Assisted Iterative-FISH defines lateral hypothalamus spatio-molecular organization

Determining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We developed Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational pipeline to rapidly process large EASI-FISH image datasets. EASI-FISH was optimized for thick brain sections (300 {micro}m) to facilitate reconstruction of spatio-molecular domains that generalize across brains. Using the EASI-FISH pipeline, we investigated the spatial distribution of dozens of molecularly defined cell types in the lateral hypothalamic area (LHA), a brain region with poorly defined anatomical organization. Mapping cell types in the LHA revealed nine novel spatially and molecularly defined subregions. EASI-FISH also facilitates iterative re-analysis of scRNA-Seq datasets to determine marker-genes that further dissociated spatial and morphological heterogeneity. The EASI-FISH pipeline democratizes mapping molecularly defined cell types, enabling discoveries about brain organization. Highlights- EASI-FISH enables robust gene expression profiling in thick brain slices - A turnkey analysis pipeline for facile analysis of large EASI-FISH image datasets - EASI-FISH reveals novel subregions of the lateral hypothalamus - Identification of rare cell types based on morphological and spatial heterogeneity

neuroscience↗

bioRxiv2019

Medial prefrontal cortex guides goal-directed decision-making about hunger and thirst

Decision-making guided by self-evaluation of bodily need states (interoception) is thought to be important for cognitive control over eating or drinking1. However, interoception of body states is notoriously unreliable2-4 because hunger and thirst have similar motivational characteristics5. Consequently, individuals may inaccurately assess their need state and consume food when dehydrated, leading some healthcare professionals to advise overweight patients to drink water before eating6-8. Neuroimaging in humans9-11 and recordings in rodents12-15 indicate medial prefrontal frontal cortex (mPFC) involvement in need state-dependent decisions about hunger and thirst, but mPFC surgical lesions16,17 and electrical activity perturbations have little influence on eating or drinking18,19. To investigate need-state dependent decision-making as well as the function of mPFC in hunger and thirst, we developed an instrumental foraging task for mice that mimics key elements of human decisions. When homeostatic need state was variable, mice did not show intrinsic knowledge of hunger or thirst state but, instead, rapidly identified their need after consumption of small portions of food and water (outcome evaluation). We observed a food-seeking bias, even in thirsty mice, that required outcome evaluation for mice to correctly seek water. mPFC was required for need state-dependent decisions about hunger and thirst, specifically under variable need state conditions. Food-seeking or water-seeking choices were controlled by multiple decision-making processes, and mPFC was involved in goal-directed decisions about the identity of need states. Thus, we have discovered a role for mPFC in decision-making about hunger and thirst, which is relevant for human behaviors that contribute to obesity.

neuroscience↗

bioRxiv2019

Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain

Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons comprise more than 75 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

neuroscience↗