Hypothalamus

Aggression can be a fundamental social behavior in many species and is importantly modulated by prior aggressive experience. However, how this experience shapes neural activity and whether it predicts behaviors in novel, more challenging aggression contexts are unknown. Moreover, imitation learning theories of aggression suggest that this behavior can be transferred through observation alone1, but whether this learning leverages the same neural mechanisms as experience is unclear. To address these two questions, here we combine novel behavioral mapping strategies with cell-type-specific and mu

…prefrontal cortex can signal to the hypothalamus to regulate sleep preparatory behaviours and sleep itself, and how other brain regions, including the ventral tegmental area, respond to psychosocial stress to induce beneficial sleep. I will also outline our work on examin

…peptide (Agrp) neurons in the hypothalamus sense hunger and promote feeding, however when food is unavailable, Agrp neurons promote adaptive behaviours by reducing anxiety and increasing food-seeking. Thus Agrp neurons respond to environmental stimuli that convey information relevant to food seeking and food detection. Indeed, food detection and consumption suppresses Agrp neural activity assessed by fibre photometry. However, when forag

The lateral septum (LS) integrates diverse subcortical and cortical inputs to generate appropriate affective behavioral responses related to fear, reward, social behaviors, and memory. Contrary to the medial septum (MS) the LS is considered an entirely GABAergic nucleus where neurons express a plethora of GABAergic markers in a partially overlapping manner. In this work, we describe a neglected and underappreciated neuronal subclass in the lateral septum expressing choline-acetyltransferase (ChAT), therefore named Lateral Septum Cholinergic Neurons (LSCNs). ChAT expressing neurons are immunohi

Prenatal alcohol exposure (PAE) leads to immune system dysfunction and increased susceptibility to autoimmune diseases. To explore potential mechanisms by which PAE induces neuroimmune dysfunction, the current study examined the impact of PAE on toll-like receptor 4 (TLR4) and TLR7/8 activation. Pregnant rats were divided into two groups: PAE - liquid ethanol diet ad libitum, and CON - pelleted control diet ad libitum. Male and female offspring were challenged in adulthood with LPS (40 µg/kg; activates TLR4), R848 (1 mg/kg; activates TLR7/8), or DMSO (vehicle), followed by brain sample collect

The third ventricle in the hypothalamus is lined by specialized glia-like cells called tanycytes. They are highly polarized cells, whose projections reach into different nuclei of the mediobasal hypothalamus and median eminence, responsible for energy homeostasis, food intake, and hormone release. Historically, tanycytes have been distinguished into alpha and beta subtypes according to their morphology and location along the ventricle. However, the classification according to localization alone does not provide information about the function of these cells. Therefore, we modified adeno-associa

Exposure to early life stress (ELS) can alter neurodevelopment and is implicated in disease risk in later life, including psychiatric and behavioural disorders. The developing brain is plastic, thus ELS may affect the development trajectory of the brain by altering processes such as neurogenesis. ELS is known to impair adult hippocampal neurogenesis, however, the brain regions, cell types and underlying molecular mechanisms altered by ELS during development are unclear. Using an optogenetic zebrafish model to elevate stress hormone levels, we analysed the effects of ELS on neurogenesis during

The hypothalamus is the central regulator of homeostasis with proopiomelanocortin (POMC) neurons in the arcuate nucleus playing a fundamental role. These neurons release neuropeptides that promote energy expenditure and satiety and are a target for leptin, an anorexigenic hormone of adipose tissue origin. POMC neurons communicate with hypothalamic astrocytes via extracellular vesicles (EVs) that contain proteins, lipids, and nucleic acids, and relay information regarding metabolic status. Our hypothesis is that astrocytes affect neuronal function and leptin signaling pathway in a nutrition-dep

…We focused on the hypothalamus, a crucial neuroendocrine stress axis (Hypothalamus-Pituitary-Adrenal axis) modulator, and studied gene expression profiles under control conditions and how ELS affects these long-term, and how sex and ELS impact the acute stress response.Mice underwent ELS by limited bedding and nesting from postnatal day (P) 2-9, then a

…that the impact of sweeteners on the hypothalamus, involved in regulating food intake [CA1] and metabolism, may be deleterious. Several studies have raised concerns about their potential effects on brain cellular metabolism (Kohno D et al.,2016), suggesting a mismatch between detection of false sugar and the energy value actually detected. This study aimed to investigate the dose-dependent impact of sweeteners on these energetic processes. Methods. Using the hypothalamic ce

Anorexia Nervosa (AN) is a multifactorial mental disorder characterized by voluntary food restriction and excessive physical activity leading to dramatic weight loss. The Brain-Derived Neurotropic Factor (BNDF) gene has been associated with AN. In rodents, both central and peripheral BDNF have been found to induce weight loss and anorexic effects. Thus, besides its function in neuronal development and mood, BDNF also acts as a metabolic regulator, making it a candidate biomarker for AN diagnosis. We used C57BL/6J female mice under 2-week 50% food restriction with access to running wheels to mi

…to appetite suppression in the hypothalamus.The study aimed to evaluate how the metabolic changes in hypothalamus, associated with obesity affect the mechanisms responsible for appetite regulation during KD treatment.Adult male mice were subjected

Specialized secretory neurons in the hypothalamus and the Edinger-Westphal nucleus secrete severalneurohormones. Very little is known about the regulation of their expression at the post-transcriptionallevel. Here we discovered that a non-canonical cytoplasmic poly(A) polymerase Tent5a is a globalpositive regulator of neurohormone expression. We detect Tent5a in Edinger-Westphal, paraventricularand supraoptic nuclei, as well as the lateral hypothalamic area. Importantly, RNA sequencing of theseregions’ biopsies, as well as northern analysis of the whole hypothalami, revealed decreased expressi

Paradoxical sleep has been named because it is a state paradoxically close to wakefulness (W) at the cortical level. In this context, our research group has shown using cFos mapping that only a few limbic cortical structures contain activated neurons during PS in contrast with W during which most of the cortical structures are activated. In the present study, we directly determine whether the same or different neurons are activated during W and PS using a new genetic approach. We mapped the neurons activated during W and PS in the transgenic TRAP2-red mouse model. Four male mice implanted wit

The dorsal raphe nucleus (DRN) contains the largest population of serotonergic (5-HT) neurons in the central nervous system. The DRN modulates a wide range of physiological functions and brain states, mostly due to its widespread and heterogeneous projections. Evidence suggests that the DRN comprises different sub-systems with distinct neurotransmitter phenotype, connectivity and function. These sub-systems are difficult to characterize in the complex mammalian DRN. To overcome this, we address these questions in zebrafish larvae, leveraging their simpler and conserved DRN.Here, we establish a

Exposure to early life stress (ELS) leads to an increased risk for psychopathology and emotional dysregulation. Knowledge on underlying mechanisms and interventions are lacking. We previously found that early methyldonor supplementation protects against ELS-induced cognitive deficits, mediated partly by HPA-axis modulation. Methyldonors are essential micronutrients and key for methyl group generation for methylation of DNA and histones. Our study aimed to understand how ELS and early micronutrient intervention affect (i) HPA-axis responsivity and anxiety/depressive-like behavior, and (ii) hypo

Overconsumption of ultra-processed food and sedentary lifestyle are the main causes of obesity, which in turn, increases the risk of developing metabolic, cardiovascular, and psychiatric diseases. Loss of control over food intake and binge eating often worsen as obesity progresses. Many studies have shown the effect of obesity on gut-microbiota composition and inflammation. However, less is known about microbiota and central adaptations occurring during the initial phases of body weight gain. To address this question, we used a rat model of binge eating, in which, rats (C/P) were fed twice a w

The hypothalamus is a complex structure involved in different body functions including the control of feeding and body energy expenditure. The arcuate nucleus (ARC), in particular, is a critical nucleus involved in these processes.In the brain, the communication and the interactions between glial and neuronal cells are fundamental in maintaining the brain metabolic homeostasis1.In particular, the Triggering Receptor Expressed on Myeloid cells 2 (Trem2), an immune receptor expressed in the brain microglia, has recently emerged as central in controlling the metabolic fitness of neurons in the de

…peptide (AgRP) neurons of the arcuate hypothalamus (Arc) but only indirectly, implicating synaptic afferents to AgRP neurons. To investigate, we developed a new method combining monosynaptic rabies with single-cell transcriptomics to identify connected neurons in a genetically tractable manner: “RAMPANT” (Rabies Afferent Mapping by Poly-A Nuclear Transcriptomics). Applying RAMPANT to A

SMC3 is a major component of the cohesin complex that regulates higher-order chromatin organization and gene expression. Human genetic studies reveal de novo mutations in SMC3 gene, found in patients with Cornelia de Lange syndrome (CdLs). This syndrome is characterized by intellectual disabilities, and behavioral patterns such as self-injury, and metabolic dysregulation. Nonetheless, little is known about the exact role of SMC3 in neuronal maintenance and gene expression especially in adulthood. This study aimed to determine the role of SMC3 in adulthood brain, using in-vivo models of adultho

…inflammation, particularly in the hypothalamus. The lingual CD36 receptor plays a crucial role in oro-gustatory perception and is downregulated in individuals with obesity. NKS-3, a non-caloric high affinity CD36 agonist, exerts systemic anti-inflammatory effects by reducing pro-inflammatory cytokines; however, its potential impact on neuroinflammation is not known. C57BL/6 male mice were fed with either a high-fat (HFD) or a standard (STD) diet for 12 wee

To circumvent the challenges of longitudinal human studies, rodents can be leveraged as they have experimentally tractable lifespans. At present, only limited number of studies have tracked longitudinal resting-state functional connectivity in rodents, with these studies only using male animals. The aim of this study is to determine sex-specific developmental trajectories of brain development using functional connectivity analysis. Male and female Wistar rats were scanned at postnatal day 28, 35, 49, 70 and 91 under light sedation. Functional connectivity was measured between several regions o

The preoptic area (POA) of the hypothalamus has garnered attention regarding its pivotal role in energy balance control and thermoregulation. Activation or inhibition of specific POA neurons has been shown to affect body temperature, locomotor activity and energy expenditure. To gain novel insights into this regulatory mechanism, we have conducted a comprehensive analysis of a distinct neuronal cluster within the POA that express the neuropeptide prepronociceptin (PNOC). Using chemogenetic techniques, we selectively activated PNOC(POA) neurons of mice and observed a significant reduction in br

Hypothalamus is the center of energy metabolism and feeding behavior, and several hypothalamic neurotransmitters regulate energy homeostasis. Neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM), were discovered as a novel neuropeptide from hypothalamus in 2014, induced obese phenotype owing to increased feeding behavior and lipogenesis in rats. However, the mechanisms of energy metabolism mediated by NPGL/NPGM system has not been totally elucidated. To investigate the loss of function of NPGL/NPGM system in mammals, we have established NPGL and NPGM double knockout mice (NPGL