BACKGROUND:​

 

Obesity is a complex, multifaceted disorder. Whilst genetic predisposition to weight gain is a major factor, the main reason for the overwhelming increase in the prevalence of obesity is the change in our environment. With increased sedentary lifestyle and consumption of processed, high-fat, calorie-dense foods, prevalence of obesity has doubled in the last few decades, reaching epidemic proportions.

 

The way we eat is tightly regulated by the brain. Different brain regions and neuronal circuits function to integrate the food cues coming from the environment and the nutritional signals released from our peripheral organs. My PhD project aims to study these circuits, define their molecular signatures and describe their role in the regulation of appetite and the way we interact with food. These characterisations will help understanding whether there are discrete brain circuits driving specific behaviours, including abnormal feeding behaviours, such as overeating or binge eating.

 

The brainstem and the hypothalamus are key brain structures involved in the detection of nutritional cues, whilst cortical and subcortical regions incorporate signals we receive from our environment. During my project I will investigate how environmental signals and homeostatic cues are integrated by neural networks to feeding behaviour and how manipulation of these signals and cues affects it. This way, we hope to understand how social settings or highly palatable foods affect our feeding behaviour, for example, why we might choose to consume food although we are feeling sated, when people we are surrounded by do so, or why we would eat a dessert even after a large meal.

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METHODOLOGY:​

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My research involves designing studies that combine behavioural neuroscience with molecular biology and endocrinology. To untangle these neuronal circuits l will perform my investigations taking advantage of the latest state-of-the art technology to manipulate neuronal activity, such as light- or drug mediated activity manipulation with optogenetics and chemogenetics; and real-time neuronal activity recording using fibre photometry. A battery of histological techniques such as IHC or FISH, will aid me to profile the molecular characteristics of these neuronal networks. In addition to this, I will use open-source software to design custom packages to acquire animal movements, detect specific behavioural features or analyse environmental interactions. Moreover, I am also interested in understanding whether these neuronal circuits and conducts present a sexual dimorphism.

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RESULTS:​

 

The purpose of my preliminary research using fluorescence and chromogenic immunohistochemistry of whole mouse brains is to create a map of neuronal activation patterns upon stimulation with different homeostatic and environmental factors. I will use this information to identify potential regions integrating multimodal information and will investigate their role in driving feeding behaviours.

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Figure 1: Neuronal activation in mouse brain tissue. Chromogenic and fluorescence immunohistochemistry using cFos, a marker of neuronal activation. A) A’) Arcuate nucleus of the hypothalamus, involved in detection of nutritional cues; B) Dorsal brainstem; B’) Nucleus of the solitary tract within the brainstem, imperative for nutritional cue integration and receiving nutritional signals from the gut via the vagal afferents (gut-brain axis).

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​​​​​​​​​FUTURE WORK: 

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I will shortly begin experimental work on my animal model, with fibre photometry and optogenetics, to identify neurones integrating selected environmental factors, which will validate the open-source software code workflow I have been working on and provide me with preliminary results which I will expand on in the future.

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FUNDED BY:​​

 

De Morentin Lab, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds 

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​​​CONTACT: 

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