A5000686786- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Neuroendocrine regulation and behavior
- Photoreceptor and optogenetics research
- Stress Responses and Cortisol
- Neurotransmitter Receptor Influence on Behavior
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Mental Health Research Topics
- Photochromic and Fluorescence Chemistry
- Genetics and Neurodevelopmental Disorders
- Decision-Making and Behavioral Economics
- Memory and Neural Mechanisms
- Neural and Behavioral Psychology Studies
- Neural dynamics and brain function
- Animal Behavior and Reproduction
- Epigenetics and DNA Methylation
- Neurobiology and Insect Physiology Research
- Single-cell and spatial transcriptomics
- Chromatin Remodeling and Cancer
- Nuclear Receptors and Signaling
- Birth, Development, and Health
- Child and Animal Learning Development
- Experimental Behavioral Economics Studies
Allen Institute for Brain Science
2022-2025
Icahn School of Medicine at Mount Sinai
2019-2025
Institut de Biologie Paris-Seine
2017-2023
Sorbonne Université
2016-2023
Inserm
2017-2023
Centre National de la Recherche Scientifique
2017-2023
University of Palermo
2023
New York Proton Center
2023
Université Paris-Seine
2020-2022
Neurosciences Paris-Seine
2017-2021
Abstract Anxiety disorders are complex diseases, and often co-occur with depression. It is as yet unclear if a common neural circuit controls anxiety-related behaviors in both anxiety-alone comorbid conditions. Here, utilizing the chronic social defeat stress (CSDS) paradigm that induces singular or combined anxiety- depressive-like phenotypes mice, we show ventral tegmental area (VTA) dopamine projecting to basolateral amygdala (BLA) selectively but not depression-like behaviors. Using...
Abstract In humans, traumatic social experiences can contribute to psychiatric disorders 1 . It is suggested that trauma impairs brain reward function such behaviour no longer rewarding, leading severe avoidance 2,3 rodents, the chronic defeat stress (CSDS) model has been used understand neurobiology underlying susceptibility versus resilience following trauma, yet little known regarding its impact on 4,5 Here we show that, CSDS, a subset of male and female mice, termed susceptible (SUS),...
Abstract Psychosocial stress has profound effects on the body, including immune system and brain 1,2 . Although a large number of pre-clinical clinical studies have linked peripheral alterations to stress-related disorders such as major depressive disorder (MDD) 3 , underlying mechanisms are not well understood. Here we show that expression circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in serum humans with MDD stress-susceptible mice following...
Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet temporal dynamic range mechanism action acetylcholine (ACh) on modulation VTA circuits reward-related behaviors are not known. Here, we used a chemical-genetic approach for rapid precise optical manipulation nicotinic neurotransmission in living mice. We provide direct evidence that ACh tone fine-tunes firing properties DA...
Abstract Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related unrelated drug seeking consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated mice the impact of chronic on midbrain dopamine neuron activity its consequence trade-off between exploitation exploration. Model-based archetypal analysis revealed substantial inter-individual variability with passively...
Abstract The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) DRN were activated male mice experienced pre-exposure a rival mouse (“social instigation”) resulting heightened intermale aggression. Both chemogenetic and optogenetic suppression of LHb-DRN projection blocked aggression after social instigation In contrast, inhibition this pathway did not affect basal levels behavior,...
Nicotine intake is likely to result from a balance between the rewarding and aversive properties of drug, yet individual differences in neural activity that control aversion nicotine their adaptation during addiction process remain largely unknown. Using two-bottle choice experiment, we observed considerable heterogeneity nicotine-drinking profiles isogenic adult male mice, with about half mice persisting consumption even at high concentrations, whereas other stopped consuming. We found was...
Glutamate is the major excitatory neurotransmitter in brain, and photochemical release of glutamate (or uncaging) a chemical technique widely used by biologists to interrogate its physiology. A basic prerequisite these optical probes bio-inertness before photolysis. However, all caged glutamates are known have strong antagonism toward receptors γ-aminobutyric acid, inhibitory transmitter. We developed probe that inert at concentrations effective for photolysis with violet light....
Those with diabetes mellitus are at high-risk of developing psychiatric disorders, especially mood yet the link between hyperglycemia and altered motivation has not been thoroughly explored. Here, we characterized value-based decision-making behavior a streptozocin-induced diabetic mouse model on Restaurant Row, naturalistic neuroeconomic foraging paradigm capable behaviorally capturing multiple decision systems known to depend dissociable neural circuits. Mice made self-paced choices daily...
Regret describes recognizing alternative actions could have led to better outcomes. It remains unclear whether regret derives from generalized mistake appraisal or instead comprises dissociable, action-specific processes. Using a neuroeconomic task, we found that mice were sensitive fundamentally distinct types of following exposure chronic social defeat stress manipulations CREB, transcription factor implicated in action. Bias make compensatory decisions after rejecting high-value offers...
Changing one's mind is a complex cognitive phenomenon involving continuous re-appraisal of the trade-off between past costs and future value. Recent work modeling this behavior across species has established associations aspects choice process their contributions to altered decision-making in psychopathology. Here, we investigated actions medial prefrontal cortex (mPFC) neurons long intergenic non-coding RNA, LINC00473, known induce stress resilience striking sex-dependent manner, but whose...
Those with diabetes mellitus are at high-risk of developing psychiatric disorders, yet the link between hyperglycemia and alterations in motivated behavior has not been explored detail. We characterized value-based decision-making a streptozocin-induced diabetic mouse model on naturalistic neuroeconomic foraging paradigm called Restaurant Row. Mice made self-paced choices while limited time-budget accepting or rejecting reward offers as function cost (delays cued by tone-pitch) subjective...
Enduring behavioral changes upon stress exposure involve in gene expression sustained by epigenetic modifications brain circuits, including the mesocorticolimbic pathway. Brahma (BRM) and Related Gene 1 (BRG1) are ATPase subunits of SWI/SNF complexes involved chromatin remodeling, a process essential to enduring plastic expression. Here, we show that mice, social defeat induces BRG1 nuclear distribution. The inactivation Brg1/Smarca4 within dopamine-innervated regions or constitutive...
Sunk cost sensitivity describes escalating decision commitment with increased spent resources. On neuroeconomic foraging tasks, mice, rats, and humans show similar escalations from sunk costs while quitting an ongoing countdown to reward. In a new analysis taken across computationally parallel tasks species laboratories, we find that these behaviors primarily occur on choices are economically inconsistent the subject's other choices, they reflect not only time spent, but also remaining,...
Hyperexcitability in the orbitofrontal cortex (OFC) is a key clinical feature of anhedonic domains Major Depressive Disorder (MDD). However, cellular and molecular substrates underlying this dysfunction remain unknown. Here, cell-population-specific chromatin accessibility profiling human OFC unexpectedly mapped genetic risk for MDD exclusively to non-neuronal cells, transcriptomic analyses revealed significant glial dysregulation region. Characterization MDD-specific cis-regulatory elements...
SUMMARY Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling, and genome-wide approaches, we uncovered a role mono-methylation of lysine 27 at histone H3 (H3K27me1) the enduring effects stress. Specifically, mice exposed to early life stress (ELS) or chronic social defeat (CSDS) adulthood displayed increased enrichment H3K27me1, transient decreases H3K27me2, nucleus accumbens (NAc), key...
Abstract Chronic stress induces changes in the periphery and central nervous system (CNS) that contribute to neuropathology behavioral abnormalities associated with psychiatric disorders. In this study, we examined impact of peripheral inflammation during chronic social defeat (CSDS) female mice. Compared male mice, found mice exhibited heightened inflammatory response identified C-C motif chemokine ligand 5 (CCL5), as a stress-susceptibility marker females. Blocking CCL5 signaling promoted...