Single-Cell Resolution of Individual Variation in Hypothalamic Neurons Allows Targeted Manipulation Affecting Social Motivation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Despite decades of research, connecting molecular and cellular phenotypes to complex behavioral traits remains an elusive goal 1 . Social motivation exhibits individual trait variation 2 , which we hypothesize is mediated by variability across hypothalamic neurons. To test this, generated single-nucleus RNA-sequencing profiles 3,4 >120,000 neurons from tuberal hypothalamus adjacent thalamus in 36 mice, balanced sex autism-associated mutation 5 with all mice assessed for social First, show that activation patterns predict behavior individuals: specifically, paraventricular Agtr1a + (angiotensin receptor 1a) predicted reduced behavior. Subsequent inhibition AGTR1A telmisartan—an FDA-approved antihypertensive 6 —improved orienting. Second, natural neuronal proportions—likely arising stochastic developmental events 7 —is sufficient shape adult even among genetically-identical identified multiple populations whose relative abundance reward-seeking Chemogenetic one such population, Nxph4 the postero-lateral 8 suppressed aspects motivation. This work establishes proof-of-principle approach where single-cell genomics precisely maps neural substrates governing revealed variations architecture deterministically influence motivation, enabled identification therapeutically-actionable targets immediate translational potential disorders deficits.

Language: Английский

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Input–output organization of the mouse BLA-projecting IL neurons

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 19, 2025

The infralimbic cortex (IL), a critical subregion within the ventromedial prefrontal (vmPFC), modulates emotion, memory, and social functions via robust projections to basolateral amygdala (BLA). However, afferent brain regions that innervate BLA-projecting IL neurons (IL-BLA PNs) their efferent targets have not been systematically characterized. We employed tracing techniques integrating adeno-associated virus (AAV) monosynaptic rabies investigate presynaptic inputs axonal outputs of IL-BLA PNs. Our findings revealed widespread synaptic PNs from subcortical areas, with strongest originating dorsomedial thalamus (MD) anterior medial (AM) in thalamic region, as well ventral hippocampus (vHPC) piriform (Pir) limbic system. Sparse labeling demonstrated collateralize various regions, including horizontal diagonal band (HDB), lateral preoptic area (LPO), pallidum (VP), hypothalamus (LH). This work establishes essential theoretical frameworks for functional investigation targeted intervention neurological disorders.

Language: Английский

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Sex-related gene expression in the posterodorsal medial amygdala of cycling female rats along with prolactin modulation of lordosis behavior

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149602 - 149602

Published: March 1, 2025

Language: Английский

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Expression of Sex‐Steroid Receptors and Sex Differences of Otp Glutamatergic Neurons of the Medial Extended Amygdala

The Journal of Comparative Neurology, Journal Year: 2025, Volume and Issue: 533(4)

Published: April 1, 2025

The medial extended amygdala (EAme) is part of the social behavior network and its subdivisions show expression sex-steroid receptors, which participate in regulation sexually dimorphic behaviors. However, EAme are highly heterogeneous terms neuron subtypes, with different subpopulations being involved aspects non-social To further understand role neurons their contribution to sexual differences, here we studied one major subtypes glutamatergic neurons, those derived from telencephalon-opto-hypothalamic domain that coexpress Otp Foxg1 genes during development. Our results showed vast majority bed nucleus stria terminalis (BSTM) both sexes express Ar, Esr1 (ERα), Esr2 (ERβ) mRNA. Moreover, high percentage receptors (between 93% 100%) indicates probably coexpressing three receptors. In addition, posterodorsal have a larger soma occupy more space males than females. These other features regarding likely contribute some behaviors regulated by EAme.

Language: Английский

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Unravelling a potential therapeutic effect of polymeric lipid-core nanoencapsulated cannabidiol on anxiety- and panic-like behaviours elicited by Bothrops jararaca lancehead pit vipers

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125747 - 125747

Published: May 1, 2025

Language: Английский

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