Biology subjects

Bosson, A.

Publications and source records attributed to Bosson, A..

4 recordsLinked to original sources

bioRxiv2024

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis

ABSTRACTLipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) in vivo. We find that LD are normally present in neurons in a non-uniform distribution across the brain, and demonstrate triglyceride metabolism enzymes and lipid droplet-associated proteins control neuronal LD formation through both canonical and recently-discovered pathways. Appropriate LD regulation in neurons has conserved and male-biased effects on whole-body energy homeostasis across flies and mice, specifically neurons that couple environmental cues with energy homeostasis. Mechanistically, LD-derived lipids support neuron function by providing phospholipids to sustain mitochondrial and endoplasmic reticulum homeostasis. Together, our work identifies a conserved role for LD as the organelle that coordinates lipid management in neurons, with implications for our understanding of mechanisms that preserve neuronal lipid homeostasis and function in health and disease. HIGHLIGHTSO_LILipid droplets (LD) normally form in neurons across species Neuronal LD are regulated by a conserved gene network C_LIO_LINeuronal LD regulation plays a conserved and sex-biased role in maintaining energy homeostasis C_LIO_LILD regulation supports ER and mitochondrial function in hunger-activated neurons C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/613929v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@1936e92org.highwire.dtl.DTLVardef@40478aorg.highwire.dtl.DTLVardef@18d5faorg.highwire.dtl.DTLVardef@882ee9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Astrocyte glucocorticoid receptors mediate sex-specific changes in activity following stress

Interactions between orexin neurons and astrocytes in the lateral hypothalamus influence activity levels including circadian and motivated behaviour. These behaviors are disrupted by stress in rodents and form a hallmark of stress-related neuropsychiatric disorders. Here we set out to understand how stress influences activity and the underlying cellular mechanisms. We report that the long-term effects of stress on activity levels correlate with spontaneous firing of orexin neurons with hyperactivity in males and hypoactivity presented by female mice. These neuronal changes were accompanied by extensive astrocyte remodelling. Causal manipulations identified lateral hypothalamic astrocytes as key regulators of activity patterns. In the context of stress, genetic deletion of glucocorticoid receptors in lateral hypothalamic astrocytes rescued the effects of stress on orexin neuron firing, restoring activity to control levels in both males and females. Overall, these data suggest that astrocytic regulation of orexin neuron firing enables the maintenance of activity levels, and their dysfunction drives stress-induced activity dysregulation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/613499v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@1e4b3b9org.highwire.dtl.DTLVardef@1d35774org.highwire.dtl.DTLVardef@12a168org.highwire.dtl.DTLVardef@122d9dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

mTORC1-mediated acquisition of reward-related spatial representations by hippocampal somatostatin interneurons

Plasticity of principal cells and inhibitory interneurons underlies hippocampal memory. Bidirectional modulation of somatostatin cell mTORC1 activity, a crucial translational control mechanism in synaptic plasticity, causes parallel changes in hippocampal CA1 somatostatin interneuron (SOM-IN) long-term potentiation and hippocampus-dependent memory, indicating a key role in learning. However, SOM-IN activity changes and behavioral correlates during learning, and the role of mTORC1 in these processes, remain ill-defined. To address these questions, we used two-photon Ca2+ imaging from SOM-INs during a virtual reality goal-directed spatial memory task in head-fixed control mice (SOM-IRES-Cre mice) or in mice with conditional knockout of Rptor (SOM-Rptor-KO mice) to block mTORC1 activity in SOM-INs. We found that control mice learn the task, but SOM-Raptor-KO mice exhibit a deficit. Also, SOM-IN Ca2+ activity became increasingly related to reward localization during learning in control mice but not in SOM-Rptor-KO mice. Four types of SOM-IN activity patterns related to reward location were observed, "reward off sustained", "reward off transient", "reward on sustained" and "reward on transient", and these responses showed global remapping after reward relocation in control but not SOM-Rptor-KO mice. Thus, SOM-INs develop mTORC1-dependent spatial coding related to learning reward localization. This coding may bi-directionally interact with pyramidal cells and other structures to represent and consolidate reward location.

neuroscience↗

bioRxiv2022

Astrocyte glucocorticoid signaling mediates cognitive impairment induced by early-life stress

Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits. Summary Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/519598v4_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1d9a228org.highwire.dtl.DTLVardef@124ff67org.highwire.dtl.DTLVardef@1fbe186org.highwire.dtl.DTLVardef@19362fb_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗