Topic: lateral hypothalamus

It was recently shown that glutamatergic neurons in the lateral hypothalamus (LHA) projecting to the lateral habenula (LH) encode negative value. However, it is still unclear how such aversive neuronal pathways located in subcortical neuronal populations affect the activity of the rest of the brain. We report here how the neuronal activity in an integrative cortical area previously reported to be involved in aversion, the medial prefrontal cortex (mPFC), is modulated when an internal aversive signal is emitted in the hypothalamic-habenula (LHA-LH) pathway. We have used a transgenic mouse line

Orexin neurons originate in the lateral hypothalamus, receive many inputs, and project throughout the brain. This puts them in an ideal position to integrate large amounts of information and signal them toward desired targets. We hypothesized that arousal, which impacts a variety of internal states and behaviours, could be one of these signals that orexin neurons transmit. To test this, we investigated the causal and correlative links between orexin neurons and pupil size, which is often taken as a readout of arousal. Optogenetic stimulation, 2-photon imaging, photometry, ablation, and pharmac

The nucleus accumbens shell (AcbSh) and ventral pallidum (VP) comprise the ventral striatopallidal system. Their connections with the lateral hypothalamus (LH) and medial prefrontal cortex (mPFC) are important in appetitively motivated behaviours and conditions like addiction. These regions have different neuronal subtypes and how they are specifically connected between them have been poorly understood. To investigate the circuitry between AcbSh, VP, LH and mPFC, we performed channelrhodopsin-assisted circuit-mapping using whole-cell patch-clamp electrophysiology and retrograde tracing in wild

Innate behaviours such as food intake, social interaction, and novel objects exploration meet multiple needs adaptively and sequentially, suggesting the existence of a hitherto elusive brain dynamics, encoding possible upcoming behaviours. Using electrophysiological neuronal recordings in freely-behaving mice, support vector machine classification and multicolor optogenetics, we show that during behavioural transitions, possible upcoming behaviours are encoded by behaviour-related phase signatures of neuronal populations in lateral hypothalamus (LH) that are active near beta oscillation (15-30

Administration of cannabinoids has been linked to changes in ingestive behaviours in rodents, in the form of hyperphagia or hypophagia. These effects have been attributed to the action of cannabinoid 1 receptors (CB1R) present in both the central nervous system and the digestive tract. While studies have observed that CB1R agonists and antagonist increase and decrease gross food intake respectively, the role of CB1R in other eating behaviours, such as food preference, is largely unknown. In two separate experiments, we tested the effects of stimulation of the CB1R located in two brain regions

Mammalian reproduction is highly energy intensive, and requires an animal to prioritize feeding or sociosexual interaction, depending on need and opportunity. We have recently shown that two leptin-sensitive populations – leptin receptor-expressing (LepRLH) and neurotensin-expressing (NtsLH) neurons of the lateral hypothalamus – act in a complementary manner to enable resistance to hunger and gate the pursuit of social needs (Petzold et al., Cell Metab 2023).Currently, using single-cell Ca2+ imaging in freely moving mice, we found that LepRLH neurons not only preferentially encoded conspecific

In the lateral hypothalamus (LH), distinct cell populations modulate innate behaviors. We investigated the role of neurotensin-expressing (Nts) neurons in the LH in balancing feeding, drinking, and social behavior across internal states.In vivo calcium imaging in freely behaving mice revealed distinct activity patterns of Nts-LH neurons associated with water and food stimuli. After prolonged food restriction, water responses were strongly enhanced, suggesting that Nts-LH neurons are involved in maintaining water intake during hunger pressure. Activation of Nts-LH neurons counteracted hunger pr

The lateral hypothalamus (LH) is emerging as a brain region of interest in Parkinson’s disease (PD). Specifically, the LH neuron populations have been shown to degenerate in PD, thus undergoing neuron loss like the substantia nigra (SN) which is a defining feature of PD that is thought to underlie observed motor symptoms. Interestingly, the LH has strong anatomical projections to the SN, but the behavioural functions associated with this projection have not been determined. We have recently shown that the LH is involved in habitual instrumental responding and spontaneous locomotor activity in

Obesity is driven and maintained by dysregulation of appetite. Especially nowadays, with rich availability of palatable processed food, overeating promotes weight gain through unbalancing energy expenditure and intake. Lifestyle interventions are foundation of obesity management; however, the long-term maintenance is challenging. Thus, understanding the neural mechanism underlying compulsive overeating is urgent for better weight control. Dopamine system and hypothalamus are highly involved in obesity, proved by fMRI in patients. In mice, our lab discovered that a specific subset of nucleus ac

Motivated behaviors such as feeding, drinking, and social behaviors, and the ability to efficiently switch between them, are essential for survival. The lateral hypothalamus (LH) plays a central role in orchestrating motivated behaviors. As there is minimal local synaptic communication within the LH, long-range synaptic input is critical to LH neural computations. In particular, the medial prefrontal cortex (mPFC), which integrates complex information about the environment, projects to the LH. However, it is unknown when mPFC to LH projection neurons are active. In this study, we combine in vi

A reduction of food intake – and concurrent loss of body weight – in combination with physical hyperactivity are main symptoms of the eating disorder anorexia nervosa. Continuous loss of fat mass results in hypoleptinemia, which initiates multiple starvation-related adaptive functions. Although leptin administration showed beneficial effects in treatment of symptoms of anorexia nervosa, including anxiety, neuronal mechanisms of possible anxiety-relieving action of leptin are not known.Here, combining calcium imaging and opto- or chemogenetics in freely behaving mice, we investigated functions

Background: The lateral hypothalamus (LH), known to play roles in modulation of reward, avoidance, and preference, projects to the associated brain regions such as the ventral tegmental area (VTA), lateral habenula (LHb), and rostromedial tegmental nucleus (RMTg). Previous studies have established that LH neurons projecting to LHb influence cocaine-induced behavior and dopamine release. However, the specific neuronal populations and the peptides involved in cocaine-induced behavioral effects have not been elucidated.Purpose: To address this, our study aimed to investigate the roles of LH neuro

Stress is an adaptive mechanism that enables an optimal response to danger. However, chronic stress disrupts normal bodily functions and can lead to various disorders. The medial prefrontal cortex (mPFC) is involved in the regulation of stress responses. One of the output targets of the mPFC is the lateral hypothalamus (LH), a brain region that regulates innate behaviours known to be affected by stress. In this work, we analysed effects of optogenetic stimulation of mPFC inputs to LH on innate behaviours in freely behaving mice exposed to different stressors.Optogenetic stimulation of mPFC pro

Accumulating evidence has substantiated that various brain functions are encoded by a sparse ensemble of experience-activated neurons. However, it remains elusive whether stress-specific ensembles ever exist and contribute to the pathogenesis of depression. Utilizing activity-dependent viral strategies, here we identified sparse stress ensembles primarily located in the middle part of the lateral hypothalamus (mLH) and the medial part of the lateral habenula (LHbM), which were universally recruited by various stressors. Remarkably, merely silencing these sparse ensembles entirely eliminated th

Accumulating evidence has substantiated that various brain functions are encoded by a sparse population of experience-activated neurons. However, it remains elusive whether stress-responsive neurons ever exist and contribute to the pathogenesis of depression. Utilizing activity-dependent viral strategies, here we identified sparse stress-responsive neurons primarily located in the middle part of the lateral hypothalamus (mLH) and the medial part of the lateral habenula (LHbM), which were universally recruited by various stressors. Remarkably, merely silencing these stress-responsive neurons en