UPCOMING SEMINARS

LORA HEISLER
UNIVERSITY OF ABERDEEN
ABERDEEN, UK
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Targeting the brain to improve obesity and type 2 diabetes

19th July
2021

16.00 UK

11.00 Eastern

The increasing prevalence of obesity and type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating energy homeostasis to accelerate the identification of new medications. Recent reports indicate that obesity medication, 5-hydroxytryptamine (5-HT, serotonin)2C receptor (5-HT2CR) agonist lorcaserin improves glycemic control in association with weight loss in obese patients with T2D. We examined whether lorcaserin has a direct effect on insulin sensitivity and how this effect is achieved. We clarify that lorcaserin dose-dependently improves glycemic control in a mouse model of T2D without altering body weight. Examining the mechanism of this effect, we reveal a necessary and sufficient neurochemical mediator of lorcaserin’s glucoregulatory effects, via activation of brain pro-opiomelanocortin (POMC) peptides. We observed that lorcaserin reduces hepatic glucose production and improves insulin sensitivity. These data suggest that lorcaserin’s action within the brain represents a mechanistically novel treatment for T2D: findings of significance to a prevalent global disease.

STACI BILBO
DUKE UNIVERSITY
DURHAM, NC, USA
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Title TBC

13th Sept
2021

16.00 UK

11.00 Eastern

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SOYOUNG Q PARK
CHARITÉ, BERLIN & GERMAN
INSTITUTE OF HUMAN NUTRITION, POTSDAM, GERMANY
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Title TBC

20th Sept
2021

16.00 UK

11.00 Eastern

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ANDREA CALIXTO
UNIVERSIDAD DE VALAPARAÍSO
VALAPARAÍSO, CHILE
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Title TBC

27th Sept
2021

16.00 UK

11.00 Eastern

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KEVIN J. TRACEY
FEINSTEIN INSTITUTES,
NORTHWELL HEALTH, MANHASSET, NY, USA
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Title TBC

4th Oct
2021

16.00 UK

11.00 Eastern

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KEN LOH
THE ROCKEFELLER UNIVERSITY
NEW YORK, NY, USA
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Title TBC

11th Oct
2021

16.00 UK

11.00 Eastern

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MARCELO DIETRICH
YALE SCHOOL OF MEDICINE
NEW HAVEN, CT, USA
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Title TBC

18th Oct
2021

16.00 UK

11.00 Eastern

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JEFFREY ILIFF
VA PUGET SOUND HEALTH CARE
UNIVERSITY OF WASHINGTON, SEATTLE, WA, USA
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Title TBC

25th Oct
2021

16.00 UK

11.00 Eastern

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PAST SEMINARS

AMITA SEHGAL
UNIVERSITY OF PENNSYLVANIA
PHILADELPHIA, PA, USA
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Why we all need a good night’s sleep

12th July 
2021

16.00 UK

11.00 Eastern

We seek to determine how circadian rhythms and sleep are integrated with physiological processes to provide optimal fitness and health. Using initially a Drosophila model, and more recently also mammalian models, we have found that aspects of the blood brain barrier (BBB) are controlled by the circadian clock. BBB properties are also influenced by sleep:wake state in Drosophila, and, in fact, appear to be contribute to functions of sleep. This and other work, which implicates sleep in the regulation of metabolic processes, is providing insights into sleep function.

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SEBASTIEN BOURET
INSERM
LILLE, FRANCE
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Importance of perinatal hormones and diet on hypothalamic development and lifelong metabolic regulation

5th July
2021

16.00 UK

11.00 Eastern

The growing prevalence of obesity and associated diseases such as type II diabetes is a major health concern, including among children. Epidemiological and animal studies suggest that alterations of the metabolic and hormonal environment during critical periods of development are associated with increased risks for obesity and type 2 diabetes in later life. There is general recognition that the developing brain is more susceptible to environmental insults than the adult brain. In particular, there is growing appreciation that developmental programming of hypothalamic neuroendocrine systems by the perinatal environment represents a possible cause for these diseases. This talk will provide an overview of evidence concerning the action of metabolic hormones (including leptin and ghrelin) in programming the development and organization of hypothalamic circuits. Recent data on the impact of maternal nutrition and low-calorie sweeteners consumption in the development and organization of hypothalamic circuits that regulate feeding and glucose homeostasis will also be presented.

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SIR STEPHEN O'RAHILLY
UNIVERSITY OF CAMBRIDGE
INSTITUTE OF METABOLIC SCIENCE, CAMBRIDGE, UK
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Some new insights into the central sensing of nutritional state and somatic stress

28th June
2021

16.00 UK

11.00 Eastern

This talk will focus on two areas. I will firstly discuss some new data, starting with insights from rare human genetic variants, which helps to clarify the role of the central melanocortin system in the acquisition of nutrients and their disposition into growth, the acquisition of lean mass and sexual maturation . I will then discuss some aspects of the emerging biology of GDF15; a sentinel hormone conveying information regarding a range of somatic stresses to the brain.

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BETH STEVENS
BOSTON CHILDREN'S HOSPITAL
HARVARD MEDICAL SCHOOL, BOSTON, MA, USA
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Neuro-Immune Coupling: How the Immune System Sculpts Brain Circuitry

21st June
2021

16.00 UK

11.00 Eastern

In this lecture, Dr Stevens will discuss recent work that implicates brain immune cells, called microglia, in sculpting of synaptic connections during development and their relevance to autism, schizophrenia and other brain disorders.Her recent work revealed a key role for microglia and a group of immune related molecules called complement in normal developmental synaptic pruning, a normal process required to establish precise brain wiring.   Emerging evidence suggests aberrant regulation of this pruning pathway may contribute to synaptic and cognitive dysfunction in a host of brain disorders, including schizophrenia. Recent research has revealed that a person’s risk of schizophrenia is increased if they inherit specific variants in complement C4, gene plays a well-known role in the immune system but also helps sculpt developing synapses in the mouse visual system (Sekar et al., 2016). Together these findings may help explain known features of schizophrenia, including reduced numbers of synapses in key cortical regions and an adolescent age of onset that corresponds with developmentally timed waves of synaptic pruning in these regions.  Stevens will discuss this and ongoing work to understand the mechanisms by which complement and microglia prune specific synapses in the brain. A deeper understanding of how these immune mechanisms mediate synaptic pruning may provide novel insight into how to protect synapses in autism and other brain disorders, including Alzheimer’s and Huntington’s Disease.

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CLEMENCE BLOUET
INSTITUTE OF METABOLIC SCIENCE
UNIVERSITY OF CAMBRIDGE, UK
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Central representations of protein availability regulating appetite and body weight control

14th June
2021

16.00 UK

11.00 Eastern

Dietary protein quantity and quality greatly impact metabolic health via evolutionary-conserved mechanisms that ensure avoidance of amino acid imbalanced food sources, promote hyperphagia when dietary protein density is low, and conversely produce satiety when dietary protein density is high. Growing evidence support the emerging concept of protein homeostasis in mammals, where protein intake is maintained within a tight range independently of energy intake to reach a target protein intake. The behavioural and neuroendocrine mechanisms underlying these adaptations are unclear and form the focus of our research.

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KEVIN MANN
STANFORD UNIVERSITY
STANFORD, CA, USA
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Causal coupling between neural activity, metabolism, and behavior across the Drosophila brain

7th June
2021

16.00 UK

11.00 Eastern

Coordinated activity across networks of neurons is a hallmark of both resting and active behavioral states in many species, including worms, flies, fish, mice and humans. These global patterns alter energy metabolism in the brain over seconds to hours, making oxygen consumption and glucose uptake widely used proxies of neural activity. However, whether changes in neural activity are causally related to changes in metabolic flux in intact circuits on the sub-second timescales associated with behavior, is unclear. Moreover, it is unclear whether differences between rest and action are associated with spatiotemporally structured changes in neuronal energy metabolism at the subcellular level. My work combines two-photon microscopy across the fruit fly brain with sensors that allow simultaneous measurements of neural activity and metabolic flux, across both resting and active behavioral states. It demonstrates that neural activity drives changes in metabolic flux, creating a tight coupling between these signals that can be measured across large-scale brain networks. Further, using local optogenetic perturbation, I show that even transient increases in neural activity result in rapid and persistent increases in cytosolic ATP, suggesting that neuronal metabolism predictively allocates resources to meet the energy demands of future neural activity. Finally, these studies reveal that the initiation of even minimal behavioral movements causes large-scale changes in the pattern of neural activity and energy metabolism, revealing unexpectedly widespread engagement of the central brain.

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MANUEL TENA-SEMPERE
IMIBIC, UNIVERSITY OF CÓRDOBA
CÓRDOBA, SPAIN
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Brain-body interactions in the metabolic/nutritional control of puberty: Neuropeptide pathways and central energy sensors.

31st May
2021

16.00 UK

11.00 Eastern

Puberty is a brain-driven phenomenon, which is under the control of sophisticated regulatory networks that integrate a large number of endogenous and environmental signals, including metabolic and nutritional cues. Puberty onset is tightly bound to the state of body energy reserves, and deregulation of energy/metabolic homeostasis is often associated with alterations in the timing of puberty. However, despite recent progress in the field, our knowledge of the specific molecular mechanisms and pathways whereby our brain decode metabolic information to modulate puberty onset remains fragmentary and incomplete.Compelling evidence, gathered over the last fifteen years, supports an essential role of hypothalamic neurons producing kisspeptins, encoded by Kiss1, in the neuroendocrine control of puberty. Kiss1 neurons are major components of the hypothalamic GnRH pulse generator, whose full activation is mandatory pubertal onset. Kiss1 neurons seemingly participate in transmitting the regulatory actions of metabolic cues on pubertal maturation. However, the modulatory influence of metabolic signals (e.g., leptin) on Kiss1 neurons might be predominantly indirect and likely involves also the interaction with other transmitters and neuronal populations.In my presentation, I will review herein recent work of our group, using preclinical models, addressing the molecular mechanisms whereby Kiss1 neurons are modulated by metabolic signals, and thereby contribute to the nutritional control of puberty. In this context, the putative roles of the energy/metabolic sensors, AMP-activated protein kinase (AMPK) and SIRT1, in the metabolic control of Kiss1 neurons and puberty will be discussed. In addition, I will summarize recent findings from our team pointing out a role of central de novo ceramide signaling in mediating the impact of obesity of (earlier) puberty onset, via non-canonical, kisspeptin-related pathways. These findings are posed of translational interest, as perturbations of these molecular pathways could contribute to the alterations of pubertal timing linked to conditions of metabolic stress in humans, ranging from malnutrition to obesity, and might become druggable targets for better management of pubertal disorders.

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CAMILLA NORD
UNIVERSITY OF CAMBRIDGE
CAMBRIDGE, UK
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The translational potential of body-brain interactions for mental health treatment

17th May
2021

16.00 UK

11.00 Eastern

Bodily experience plays a role in the genesis of symptoms across many mental health conditions, including anxiety disorders, eating disorders, and mood disorders. Targeting bodily signals or their interpretation could represent a distinct avenue for treatment. But how should novel treatments be developed? This talk will take two approaches to developing treatments for brain-body interactions in mental health disorders. First, I will discuss an experimental medicine study in health controls (Nord & Dalmaijer et al, 2021 Current Biology). In this study, we used a pharmacological manipulation of gastric state (the anti-emetic domperidone), and measured its effects on an implicit measure of disgust avoidance, oculomotor behaviour. We found domperidone weakened the ‘immunity’ of disgust avoidance to habituation after prolonged, incentivised exposure. This could have translational implications for future therapeutic interventions. Next, I will discuss a neuroimaging analysis of existing interoceptive datasets in diverse psychiatric populations (Nord et al., In Press, The American Journal of Psychiatry). Using activation likelihood estimation meta-analysis, we discovered that a common neural locus underpins transdiagnostic interoceptive differences (across patients with bipolar disorder, anxiety, major depression, anorexia, and schizophrenia). This locus could represent a putative neural target for intervention development. I will end with a conceptual model of mental health treatment development, emphasising the key role that cognitive neuroscience could play in forward- and back-translational science.

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CHRISTOPH SCHEIERMANN
LMU MUNICH, GERMANY
UNIVERSITÉ DE GENÈVE, SWITZERLAND
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Sympathetic control of lymph node function

3rd May
2021

16.00 UK

11.00 Eastern

Peripheral nerve injury can cause debilitating disease and immune-cell mediated destruction of the affected nerve. While the focus of most studies has been on the nerve-degenerative response, the effect of loss of innervation on lymph node function is largely unclear. Here, I will discuss the cellular and molecular events caused by local denervation and loss of direct neural input to the popliteal lymph node that induce an inflammatory response and lymph node expansion.

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SUPRIYA SRINIVASAN
SCRIPPS RESEARCH
LA JOLLA, CA, USA
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Communication between the brain and the gut:
Learnings from C. elegans

19th Apr
2021

16.00 UK

11.00 Eastern

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DOUGLAS A. BAYLISS
UNIVERSITY OF VIRGINIA
CHARLOTTESVILLE, VA, USA
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The retrotrapezoid nucleus: an integrative and interoceptive hub in neural control of breathing

12th Apr
2021

16.00 UK

11.00 Eastern

In this presentation, we will discuss the cellular and molecular properties of the retrotrapezoid nucleus (RTN), an integrative and interoceptive control node for the respiratory motor system. We will present the molecular profiling that has allowed definitive identification of a cluster of tonically active neurons that provide a requisite drive to the respiratory central pattern generator (CPG) and other pre-motor neurons. We will discuss the ionic basis for steady pacemaker-like firing, including by a large subthreshold oscillation; and for neuromodulatory influences on RTN activity, including by arousal state-dependent neurotransmitters and CO2/H+. The CO2/H+-dependent modulation of RTN excitability represents the sensory component of a homeostatic system by which the brain regulates breathing to maintain blood gases and tissue pH; it relies on two intrinsic molecular proton detectors, both a proton-activated G protein-coupled receptor (GPR4) and a proton-inhibited background K+ channel (TASK-2). We will also discuss downstream neurotransmitter signaling to the respiratory CPG, focusing especially on a newly-identified peptidergic modulation of the preBötzinger complex that becomes activated following birth and the initiation of air breathing. Finally, we will suggest how the cellular and molecular properties of RTN neurons identified in rodent models may contribute to understanding human respiratory disorders, such as congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS).

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DRAGANA ROGULJA
HARVARD MEDICAL SCHOOL
BOSTON, MA, USA
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Sleep and the gut

5th Apr
2021

16.00 UK

11.00 Eastern

Sleep is generally associated with the brain but poor sleep impacts the entire body - many diseases are caused or exacerbated by sleep loss. Our work is uncovering ways in which sleep and the body interact. We found a special, two-way relationship between sleep and the gut: the gut is uniquely impacted by sleep loss, and it actively controls sleep quality. These findings could help us understand the origins of sleep as well as develop strategies to offset the negative consequences of inadequate sleep.

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DANIELA CARNEVALE
SAPIENZA UNVERSITY OF ROME
ROME, ITALY
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Neuroimmune interactions in Cardiovascular Diseases

29th Mar
2021

16.00 UK

11.00 Eastern

The nervous system and the immune system share the common ability to exert gatekeeper roles at the interfaces between internal and external environment. Although interaction between these two evolutionarily highly conserved systems is long recognized, the pathophysiological mechanisms regulating their reciprocal crosstalk in cardiovascular diseases became object of investigation only more recently. In the last years, our group elucidated how the autonomic nervous system controls the splenic immunity recruited by hypertensive challenges. In my talk, I will focus on the molecular mechanisms that regulate the neuro-immune crosstalk in hypertension. I will elaborate on the mechanistic insights into this brain-spleen axis led us uncover a new molecular pathway mediating the neuroimmune interaction established by noradrenergic-mediated release in the spleen of placental growth factor (PlGF), an angiogenic growth factor potentially targetable with pharmacological approaches.

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JOHN F. CRYAN
UNIVERSITY COLLEGE CORK
CORK, IRELAND
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Gut Feelings: The Microbiota-Gut-Brain Axis Across the Lifespan

22nd Mar
2021

16.00 UK

12.00 Eastern

The microbiota-gut-brain axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of brain development and behaviour during early life, adolescence & ageing. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. Studies in animal models have shown that the development of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics.   Recently, the gut microbiota has been implicated in regulating the stress response, and social behaviour.  Moreover, fundamental brain processes from adult hippocampal neurogenesis to myelination to microglia activation have been shown to be regulated by the microbiome. Further studies will focus on understanding the mechanisms underlying such brain effects and how they can be exploited by microbiota-targeted interventions including ‘psychobiotics’ and diet.

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KARA MARSHALL
SCRIPPS RESEARCH
LA JOLLA, CA, USA
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Under Pressure: the role of PIEZO ion channels in interoception

1st Mar
2021

16.00 UK

11.00 Eastern

PIEZO ion channels detect force in cellular membranes. They are expressed in a wide variety of mammalian tissues, including the vasculature, lymphatic system, and the nervous system. We have found that PIEZO2 in sensory neurons is required for the mechanical senses of touch and proprioception, but our understanding of internal organ sensing, interoception, is far behind. I will describe our findings on the role of PIEZO ion channels in the lesser-known interoceptive senses in multiple organ systems.

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ANNA MOLOFSKY
UNIVERSITY OF CALIFORNIA, SAN
FRANCISCO, CA, USA
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Microglia, memories, and the extracellular space

22nd Feb
2021

16.00 UK

11.00 Eastern

Microglia are the immune cells of the brain, and play increasingly appreciated roles in synapse formation, brain plasticity, and cognition. A growing appreciation that the immune system involved in diseases like schizophrenia, epilepsy, and neurodegenerative diseases has led to renewed interest in how microglia regulate synaptic connectivity. Our group previously identified the IL-1 family cytokine Interleukin-33 (IL-33) as a novel regulator of microglial activation and function. I will discuss a mechanism by which microglia regulate synaptic plasticity and long-term memories by engulfing brain extracellular matrix (ECM) proteins. These studies raise the question of how these pathways may be altered or could be modified in the context of disease.

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MICAH ALLEN
AARHUS UNIVERSITY
AARHUS, DENMARK
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Towards better interoceptive biomarkers in computational psychiatry

15th Feb
2021

16.00 UK

11.00 Eastern

Empirical evidence and theoretical models both increasingly emphasize the importance of interoceptive processing in mental health. Indeed, many mood and psychiatric disorders involve disturbed feelings and/or beliefs about the visceral body. However, current methods to measure interoceptive ability are limited in a number of ways, restricting the utility and interpretation of interoceptive biomarkers in psychiatry. I will present some newly developed measures and models which aim to improve our understanding of disordered brain-body interaction in psychiatric illnesses.

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ALIA CRUM
STANFORD UNIVERSITY
PALO ALTO, CA, USA
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Harnessing Mindset in 21st Century Healthcare

1st Feb
2021

16.00 UK

11.00 Eastern

Mindsets are core assumptions about the nature and workings of things in the world that orient us to a particular set of attributions, expectations, and goals. Our study of mindsets is, in part, inspired by research on the placebo effect, a robust demonstration of the ability of mindsets, conscious or subconscious, to elicit physiological changes in the body. This talk will explore the role of mindsets in three stages of chronic disease progression: genetic predisposition, behavioral prevention, and clinical treatment. I will discuss the mechanisms through which mindsets influence health as well as the myriad ways that mindsets can be more effectively leveraged to motivate healthy behaviors and improve 21st century healthcare. 

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KATERINA AKASSOGLOU
GLADSTONE INSTITUTE FOR NEURO-
LOGICAL DISEASE, SAN FRANCISCO, CA, USA
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Neurovascular Interactions: Mechanisms, Imaging, Therapeutics

25th Jan
2021

16.00 UK

11.00 Eastern

The communication between the brain, immune and vascular systems is a key contributor to the onset and progression of neurological diseases. Dr. Akassoglou identified the coagulation factor fibrinogen as a blood-derived driver for neuroinflammation and inhibitor of myelin repair in a wide range of neurologic diseases, such as multiple sclerosis, Alzheimer’s disease and brain trauma. By developing cutting-edge imaging tools to study the neurovascular interface, her lab showed that microglia dynamic brain surveillance maintain neuronal network synchronization within a physiological range preventing hyperexcitability and identified fibrinogen as a new culprit for microglia-mediated oxidative stress-dependent spine elimination and cognitive impairment. By developing Tox-Seq, her lab reported the oxidative stress innate immune cell atlas in neuroinflammation. Her lab developed a first-in-class fibrin-targeting immunotherapy to selectively target inflammatory functions of fibrin without interference with clotting with efficacy in autoimmune- and amyloid-driven neurotoxicity. These findings could be a common thread for the understanding of the etiology, progression, and development of new treatments for neurologic diseases with neuroimmune and cerebrovascular dysfunction.

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RYUSUKE NIWA
UNIVERSITY OF TSUKUBA
TSUKUBA, JAPAN
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Neuroendocrine control of female germline stem cell increase in Drosophila melanogaster

11th Jan
2021

16.00 UK

11.00 Eastern

The development and maintenance of many tissues are fueled by stem cells. Many studies have addressed how intrinsic factors and local signals from neighboring niche cells maintain stem cell identity and proliferative potential. In contrast, it is poorly understood how stem cell activity is controlled by systemic, tissue-extrinsic signals in response to environmental cues and changes in physiological status. Our laboratory has been focusing on female germline stem cells (fGSCs) in the fruit fly Drosophila melanogaster as a model system and studying neuroendocrine control of fGSC increase. The increase of fGSCs is induced by mating stimuli. We have previously reported that mating-induced fGSC increase is regulated by the ovarian steroid hormone and the enteroendocrine peptide hormone [Ameku & Niwa, PLOS Genetics 2016; Ameku et al. PLOS Biology 2018].

In this presentation, we report our recent finding showing a neuronal mechanism of mating-induced fGSC increase. We first found that the ovarian somatic cell-specific RNAi for Oamb, a G protein-coupled receptor for the neurotransmitter octopamine, failed to induce fGSC proliferation after mating. Both ex vivo and in vivo experiments revealed that octopamine and Oamb positively regulated mating-induced fGSC increase via intracellular Ca 2+ signaling. We also found that a small subset of octopaminergic neurons directly projected to the ovary, and neuronal activity of these neurons was required for mating-induced fGSC increase. This study provides a mechanism describing how the neuronal system controls stem cell behavior through stem cell niche signaling [Yoshinari et al. eLife 2020].

Here I will also present our recent data showing how the neuroendocrine system couples fGSC behavior to multiple environmental cues, such as mating and nutrition.

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GÉRARD KARSENTY
COLUMBIA UNIVERSITY
NEW YORK, NY, USA
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Blurring the boundaries between neuroscience and organismal physiology

14th Dec
2020

16.00 UK

11.00 Eastern

Work in my laboratory is based on the assumptions that we do not know yet how all physiological functions are regulated and that mouse genetics by allowing to identify novel inter-organ communications is the most efficient ways to identify novel regulation of physiological functions. We test these two contention through the study of bone which is the organ my lab has studied since its inception. Based on precise cell biological and clinical reasons that will be presented during the seminar we hypothesized that bone should be a regulator of energy metabolism and reproduction and identified a bone-derived hormone termed osteocalcin that is responsible of these regulatory events. The study of this hormone revealed that in addition to its predicted functions it also regulates brain size, hippocampus development, prevents anxiety and depression and favors spatial learning and memory by signaling through a specific receptor we characterized. As will be presented, we elucidated some of the molecular events accounting for the influence of osteocalcin on brain and showed that maternal osteocalcin is the pool of this hormone that affects brain development. Subsequently and looking at all the physiological functions regulated by osteocalcin, i.e., memory, the ability to exercise, glucose metabolism, the regulation of testosterone biosynthesis, we realized that are all need or regulated in the case of danger. In other words it suggested that osteocalcin is an hormone needed to sense and overcome acute danger. Consonant with this hypothesis we next showed this led us to demonstrate that bone via osteocalcin is needed to mount an acute stress response through molecular and cellular mechanisms that will be presented during the seminar. Overall, an evolutionary appraisal of bone biology, this body of work and experiments ongoing in the lab concur to suggest 1] the appearance of bone during evolution has changed how physiological functions as diverse as memory, the acute stress response but also exercise and glucose metabolism are regulated and 2] identified bone and osteocalcin as its molecular vector, as an organ needed to sense and response to danger.

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ELAINE HSIAO
UNIVERSITY OF CALIFORNIA,
LOS ANGELES, CA, USA
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Interactions between the microbiome and nervous system during early development

10th Dec
2020

15.00 UK

10.00 Eastern

Elaine Hsiao is De Logi Associate Professor of Biological Sciences at UCLA, where she leads a lab studying interactions between the gut microbiome, brain and behavior. Their research identified roles for the gut microbiome in modulating immune dysregulation and social behavior, regulating intestinal motility by controlling serotonin biosynthesis, and mediating the anti-seizure effects of the ketogenic diet.

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DIEGO V. BOHORQUEZ
DUKE UNIVERSITY
DURHAM, NC, USA
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A gut choice

7th Dec
2020

16.00 UK

11.00 Eastern

I am a neuroscientist recognized for the discovery of a neural circuit that serves as the basis of gut brain sensory transduction. At Duke University, I lead a research team built with the vision to treat the brain from the gut. Our mission is to dissect gut-brain circuits underlying behaviors to improve health (www.gutbrains.com). Beyond the laboratory, in 2015, I founded Gastronauts - a venue to disseminate knowledge on gut brain matters (www.thinkgastronauts.com).

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LISA STOWERS
SCRIPPS RESEARCH
SAN DIEGO, CA, USA
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Leveraging olfaction to understand how the brain and the body generate social behavior

30th Nov
2020

16.00 UK

11.00 Eastern

Courtship behavior is an innate model for many types of brain computations including sensory detection, learning and memory, and internal state modulation. Despite the robustness of the behavior, we have little understanding of the underlying neural circuits and mechanisms. The Stowers’ lab is leveraging the ability of specialized olfactory cues, pheromones, to specifically activate and therefore identify and study courtship circuits in the mouse. We are interested in identifying general circuit principles (specific brain nodes and information flow) that are common to all individuals, in order to additionally study how experience, gender, age, and internal state modulate and personalize behavior. We are solving two parallel sensory to motor courtship circuits, that promote social vocal calling and scent marking, to study information processing of behavior as a complete unit instead of restricting focus to a single brain region. We expect comparing and contrasting the coding logic of two courtship motor behaviors will begin to shed light on general principles of how the brain senses context, weighs experience and responds to internal state to ultimately decide appropriate action.

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LISA BEUTLER
NORTHWESTERN UNIVERSITY
CHICAGO, IL, USA
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Long-term effects of diet-induced obesity on gut-brain communication

23rd Nov
2020

16.00 UK

11.00 Eastern

Rapid communication between the gut and the brain about recently consumed nutrients is critical for regulating food intake and maintaining energy homeostasis. We have shown that the infusion of nutrients directly into the gastrointestinal tract rapidly inhibits hunger-promoting AgRP neurons in the arcuate nucleus of the hypothalamus and suppresses subsequent feeding. The mechanism of this inhibition appears to be dependent upon macronutrient content, and can be recapitulated by a several hormones secreted in the gut in response to nutrient ingestion. In high-fat diet-induced obese mice, the response of AgRP neurons to nutrient-related stimuli are broadly attenuated. This attenuation is largely irreversible following weight loss and may represent a mechanism underlying difficulty with weight loss and propensity for weight regain in obesity.

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PIERRE LÉOPOLD
INSTITUT CURIE
PARIS, FRANCE
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Adjusting organ size during Drosophila development:
how and why?

9th Nov
2020

16.00 UK

11.00 Eastern

Body and organ size are intrinsic properties of living organisms and are intimately linked to the developmental program to produce fit individuals with proper proportions. An aspect of growth control and size determination has emerged recently with the re-evaluation of classical studies on transplantation and tissue regeneration, raising questions about the determination of final tissue size, the cessation of growth and the coupling between tissue growth and the developmental program. Using the Drosophila model, we identified a neural circuitry that is required for inducing a developmental delay in conditions of tissue growth impairment, whereby the hormone Dilp8 delays maturation by acting on its receptor Lgr3 in specific brain neurons, preventing the production of the steroid hormone ecdysone. Interestingly, animals lacking Dilp8 show increased developmental noise, characterized by strong intra- and inter-individual variations in organ size. I will present our recent data addressing the mechanisms of actions of this novel hormonal circuit controlling both the coupling between organ growth and developmental time, as well as the determination of accurate final organ size.

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YOAV LIVNEH
WEIZMANN INSTITUTE OF SCIENCE
REHOVOT, ISRAEL
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Cortical estimation of current and future bodily states

2nd Nov
2020

16.00 UK

11.00 Eastern

Interoception, the sense of internal bodily signals, is essential for physiological homeostasis, cognition, and emotions. Human neuroimaging studies suggest insular cortex plays a central role in interoception, yet the cellular and circuit mechanisms of its involvement remain unclear. We developed a microprism-based cellular imaging approach to monitor insular cortex activity in behaving mice across different physiological need states. We combine this imaging approach with manipulations of peripheral physiology, circuit-mapping, cell type-specific and circuit-specific manipulation approaches to investigate the underlying circuit mechanisms. I will present our recent data investigating insular cortex activity during two physiological need states – hunger and thirst. These were induced naturally by caloric/fluid deficiency, or artificially by activation of specific hypothalamic “hunger neurons” and “thirst neurons”. We found that insular cortex ongoing activity faithfully represents current physiological state, independently of behavior or arousal levels. In contrast, transient responses to learned food- or water-predicting cues reflect a population-level “simulation” of future predicted satiety. Together with additional circuit-mapping and manipulation experiments, our findings suggest that insular cortex integrates visceral-sensory inputs regarding current physiological state with hypothalamus-gated amygdala inputs signaling availability of food/water. This way, insular cortex computes a prediction of future physiological state that can be used to guide behavioral choice.

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MICHAEL O'DONNELL
YALE UNIVERSITY
NEW HAVEN, CT, USA
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Modulation of C. elegans behavior by gut microbes

26th Oct
2020

15.00 UK

11.00 Eastern

We are interested in understanding how microbes impact the behavior of host animals. Animal nervous systems likely evolved in environments richly surrounded by microbes, yet the impact of bacteria on nervous system function has been relatively under-studied. A challenge has been to identify systems in which both host and microbe are amenable to genetic manipulation, and which enable high-throughput behavioral screening in response to defined and naturalistic conditions. To accomplish these goals, we use an animal host — the roundworm C. elegans, which feeds on bacteria — in combination with its natural gut microbiome to identify inter-organismal signals driving host-microbe interactions and decision-making. C. elegans has some of the most extensive molecular, neurobiological and genetic tools of any multicellular eukaryote, and, coupled with the ease of gnotobiotic culture in these worms, represents a highly attractive system in which to study microbial influence on host behavior. Using this system, we discovered that commensal bacterial metabolites directly modulate nervous system function of their host. Beneficial gut microbes of the genus Providencia produce the neuromodulator tyramine in the C. elegans intestine. Using a combination of behavioral analysis, neurogenetics, metabolomics and bacterial genetics we established that bacterially produced tyramine is converted to octopamine in C. elegans, which acts directly in sensory neurons to reduce odor aversion and increase sensory preference for Providencia. We think that this type of sensory modulation may increase association of C. elegans with these microbes, increasing availability of this nutrient-rich food source for the worm and its progeny, while facilitating dispersal of the bacteria.

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DANIEL MUCIDA
THE ROCKEFELLER UNIVERSITY
NEW YORK, NY, USA
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Neuro-immune interactions in the gut

19th Oct
2020

16.00 UK

11.00 Eastern

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BRAD DICKERSON
UNIVERSITY OF NORTH CAROLINA
CHAPEL HILL, NC, USA
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An evolutionarily conserved hindwing circuit mediates Drosophila flight control

12th Oct
2020

16.00 UK

11.00 Eastern

My research at the interface of neurobiology, biomechanics, and behavior seeks to understand how the timing precision of sensory input structures locomotor output. My lab studies the flight behavior of the fruit fly, Drosophila melanogaster, combining powerful genetic tools available for labeling and manipulating neural circuits with cutting-edge imaging in awake, behaving animals. This work has the potential to fundamentally reshape understanding of the evolution of insect flight, as well as highlight the tremendous importance of timing in the context of locomotion.Timing is crucial to the nervous system. The ability to rapidly detect and process subtle disturbances in the environment determines whether an animal can attain its next meal or successfully navigate complex, unpredictable terrain. While previous work on various animals has made tremendous strides uncovering the specialized neural circuits used to resolve timing differences with sub-microsecond resolution, it has focused on the detection of timing differences in sensory systems. Understanding of how the timing of motor output is structured by precise sensory input remains poor. My research focuses on an organ unique to fruit flies, called the haltere, that serves as a bridge for detecting and acting on subtle timing differences, helping flies execute rapid maneuvers. Understanding how this relatively simple insect canperform such impressive aerial feats demands an integrative approach that combines physics, muscle mechanics, neuroscience, and behavior. This unique, powerful approach will reveal the general principles that govern sensorimotor processing.

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JONATHAN KIPNIS
WASHINGTON UNIVERSITY
ST LOUIS, MO, USA
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Meningeal lymphatics and peripheral immunity in brain function and dysfunction

5th Oct
2020

16.00 UK

11.00 Eastern

Immune cells and their derived molecules have major impact on brain function. Mice deficient in adaptive immunity have impaired cognitive and social function compared to that of wild-type mice. Importantly, replenishment of the T cell compartment in immune deficient mice restored proper brain function. Despite the robust influence on brain function, T cells are not found within the brain parenchyma, a fact that only adds more mystery into these enigmatic interactions between T cells and the brain. Our results suggest that meningeal space, surrounding the brain, is the site where CNS-associated immune activity takes place. We have recently discovered a presence of meningeal lymphatic vessels that drain CNS molecules and immune cells to the deep cervical lymph nodes. This communication between the CNS and the peripheral immunity is playing a key role in neurophysiology and in several CNS disorders. Interestingly, meningeal lymphatics are impaired in aging and their dysfunction may be related to age-related cognitive decline as well as to Alzheimer’s pathology. In addition to providing new insights into age-related disorders, meningeal lymphatics may also serve as a novel therapeutic target for these diseases and are worth of in-depth mechanistic exploration.

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STEFANIE SCHIRMEIER
UNIVERSITY OF MÜNSTER
MÜNSTER, GERMANY
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Glia-neuron metabolic interactions in Drosophila

28th Sept
2020

16.00 UK

11.00 Eastern

To function properly, the nervous system consumes vast amounts of energy, which is mostly provided by carbohydrate metabolism. Neurons are very sensitive to changes in the extracellular fluid surrounding them, which necessitated shielding of the nervous system from fluctuating solute concentrations in circulation. This is achieved by the blood-brain barrier (BBB) that prevents paracellular diffusion of solutes into the nervous system. This in turn also means that all nutrients that are needed e.g. for sufficient energy supply need to be transported over the BBB. We use Drosophila as a model system to better understand the metabolic homeostasis in the central nervous system.

Glial cells play essential roles in both nutrient uptake and neural energy metabolism. Carbohydrate transport over the glial BBB is well-regulated and can be adapted to changes in carbohydrate availability. Furthermore, Drosophila glial cell are highly glycolytic cells that support the rather oxidative metabolism of neurons. Upon perturbations of carbohydrate metabolism, the glial cells prove to be metabolically very flexible and able to adapt to changing circumstances. I will summarize what we know about carbohydrate transport at the Drosophila BBB and about the metabolic coupling between neurons and glial cells. Our data shows that many basic features of neural metabolism are well conserved between the fly and mammals.

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ISAAC CHIU
HARVARD MEDICAL SCHOOL
BOSTON, MA, USA
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Neuro-immune interactions in pain and host defence

21st Sept
2020

16.00 UK

11.00 Eastern

The Chiu laboratory focuses on neuro-immune interactions in pain, itch, and tissue inflammation. Dr. Chiu’s research has uncovered molecular interactions between the nervous system, the immune system and microbes that modulates host defense. He has found that sensory neurons can directly detect bacterial pathogens and their toxins to produce pain. Neurons in turn release neuropeptides that modulate immune cells in host defense. These interactions occur at major tissue barriers in the body including the gut, skin and lungs. In this talk, he will discuss these major neuro-immune interactions and how understanding them could lead to novel approaches to treat pain or inflammation.

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IRENE MIGUEL-ALIAGA
IMPERIAL COLLEGE
LONDON, UK
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Sex, guts and babies: the plasticity of the adult intestine and its neurons

14th Sept
2020

16.00 UK

11.00 Eastern

Internal organs constantly exchange signals, and can respond with striking anatomical and functional transformations, even in fully developed organisms. We are exploring the mechanisms that drive and sustain such plasticity using the intestine and its neurons as experimental systems. I will present some of our recent work, which has characterised the enteric nervous system of Drosophila, and has explored its physiological plasticity as well as that of the intestine itself. This work has uncovered unexpected sexual dimorphisms, intestinal contributions to reproductive success and metabolic crosstalk between the gut and the brain. Interestingly, this crosstalk appears to be spatially constrained by the three dimensional arrangement of viscera, revealing a previously unrecognised layer of inter-organ signalling regulation. I may also describe our attempts to explore how broadly applicable our findings may be using mammalian systems.

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STEPHEN J. SIMPSON
CHARLES PERKINS CENTRE
UNIVERSITY OF SYDNEY, AUSTRALIA
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Towards resolving the Protein Paradox in longevity and late-life health

7th Sept
2020

10.00 UK

05.00 Eastern

Reducing protein intake (and that of key amino acids) extends lifespan, especially during mid-life and early late-life. Yet, due to a powerful protein appetite, reducing protein in the diet leads to increased food intake, promoting obesity – which shortens lifespan. That is the protein paradox. In the talk I will bring together pieces of the jigsaw, including: specific nutrient appetites, protein leverage, macronutrient interactions on appetite and ageing, the role of branched-chain amino acids and FGF-21, and then I will conclude by showing how these pieces fit together and play out in the modern industrialised food environment to result in the global pandemic of obesity and metabolic disease.

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MONICA DUS
UNIVERSITY OF MICHIGAN
ANN ARBOR, MI, USA
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Epigenetic Reprogramming of Taste by Diet.

20th July
2020

16.00 UK

11.00 Eastern

Diets rich in sugar, salt, and fat alter taste perception and food intake, leading to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons of D. melanogaster flies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Importantly, half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity.

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MICHAL SCHWARTZ
WEIZMANN INSTITUTE OF SCIENCE
REHOVOT, ISRAEL
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Novel immunotherapy to treat Alzheimer’s disease and Dementia: from curiosity-driven research to prospect of therapy

29th June
2020

16.00 UK

11.00 Eastern

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STEPHEN LIBERLES
HARVARD MEDICAL SCHOOL
BOSTON, MA, USA
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Vagal sensory neurons that guard the airways.

22nd June
2020

16.00 UK

11.00 Eastern

The vagus nerve contains a diversity of sensory neurons that detect peripheral stimuli such as blood pressure changes at the aortic arch, lung expansion during breathing, meal-induced stomach distension, and chemotherapeutics that induce nausea. Underlying vagal sensory mechanisms are largely unresolved at a molecular level, presenting tremendously important problems in sensory biology. We charted vagal sensory neurons by single cell RNA sequencing, identifying novel cell surface receptors and classifying a staggering diversity of sensory neuron types. We then generated a collection of ires-Cre knock-in mice to target each neuron type, and adapted genetic tools for Cre-based anatomical mapping, in vivo imaging, targeted ablation, and optogenetic control of vagal neuron activity. We found different sensory neuron types that innervate the lung and exert powerful effects on breathing, others that monitor and control the digestive system, and yet others that innervate that innervate the larynx and protect the airways. Together with Ardem Patapoutian, we also identified a critical role for Piezo mechanoreceptors in the sensation of airway stretch, which underlies a classical respiratory reflex termed the Hering-Breuer inspiratory reflex, as well as in the neuronal sensation of blood pressure and the baroreceptor reflex.

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