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Dynamic regulation of cortical information processing and energy expenditure by food availability

Reference	BB/T007907/1
Principal Investigator / Supervisor	Dr Nathalie Louise Isabelle Rochefort
Co-Investigators / Co-Supervisors	Dr Zahid Padamsey
Institution	University of Edinburgh
Department	Centre for Discovery Brain Sciences
Funding type	Research
Value (£)	506,753
Status	Current
Type	Research Grant
Start date	01/10/2020
End date	05/01/2024
Duration	39 months

Abstract

Electrical signalling in neuronal networks is energetically costly. Scarcity of food throughout evolution has sculpted efficient information coding strategies in the brain to optimize energy usage. However, it remains unclear whether these neuronal coding strategies are fixed, or whether they are dynamically regulated by resource availability in the environment. We predict that food restriction decreases information processing in order to save energy. To test this, we will use the mouse primary visual cortex (V1) as a model system to understand how food availability affects information processing and energy consumption in cortical networks. Our preliminary two-photon Ca2+ imaging data show that food restriction broadens orientation and spatial tuning of V1 layer 2/3 neurons, in awake mice. These changes correlate with a decreased ability to decode natural scenes using V1 activity, consistent with a decrease in network information processing. We will test whether these changes are associated with energy savings (i.e. reduced ATP consumption), how they are mediated by cellular/synaptic changes, and whether they correlate with visual discrimination deficits. Our study has four aims: 1) characterize the effect of food restriction on V1 response properties and information coding using two-photon Ca2+ imaging, 2) characterize the impact of food restriction on ATP expenditure of V1 neurons in vivo using ATP sensors and whole-cell recordings 3) characterize the cellular/synaptic electrophysiological properties underlying food restriction-induced changes in V1 processing and energy consumption using in vivo whole-cell recordings 4) assess the behavioural significance of food restriction on visual perception. These results will reveal fundamental principles by which energy availability regulates cortical function. This will be critical for understanding how diet regulates brain function, and ultimately for optimizing diets for life-long cognitive function.

Summary

What we eat greatly impacts our brain function. Most people have experienced the feeling of being less able to concentrate or getting grumpy when they are hungry. This is because our brains need many calories to function. Despite only comprising 2% of the body mass, the brain utilizes 20% of the energy we consume daily, meaning that, by weight, it is the most energetically expensive organ. When food intake is reduced, organs such as muscles, reduce their performance in order to save energy. We predict that the brain is no different, and that when food intake is reduced, the brain should similarly reduce its performance in order to save energy. We will test this prediction in mice, as an animal model of mammalian brain function that allows us to study the cellular mechanisms underlying this process. To do so, we will reduce the calorie intake of mice by 20-25% and will record the activity of neurons within their brain, specifically within the visual cortex, which processes visual information. Our preliminary data show that calorie restriction reduces the function of the visual cortex, in line with our prediction. In our study, we will further explore these changes, and examine if they help the brain to save energy when calorie intake is reduced. We next want to understand the molecules and hormones responsible for linking changes in caloric intake with changes in brain function. Finally, we want to understand to what extent reductions in brain function during calorie restriction actually impact behaviour. Specifically, in our study, we will test how reductions in the function of the visual cortex during calorie restriction affect visual ability in mice. Overall, our study will help us to understand how calorie intake impacts brain function and energy consumption. This work will be important for understanding how best to adapt human diet to improve life-long cognitive function, which would benefit quality of life and economic productivity, and would reduce health costs. Our study may also reveal potential drug targets for improving brain function and energy use.

Impact Summary

Diet has a profound impact on human health and cognitive function. Our study explores the impact of food availability on cortical information processing and energy consumption. Critically, it will establish a mechanistic and theoretical framework for understanding the impact of caloric intake on cognitive function, with the overarching hypothesis that the brain regulates information processing to maintain energy homeostasis. Such a framework has the potential to provide a clear understanding of how and why diet impacts brain function. This would be important for understanding how best to design human diet to improve life-long cognitive function, which would benefit quality of life and economic productivity, and would reduce health costs. Our study may also reveal potential drug targets for improving brain function and energy use. Our work, therefore, will be of benefit to members of the health & pharmaceutical industry, policy makers, medical professionals, nutritionists, and the general public. 1) Health & pharmaceutical industry - Our study, by providing mechanistic insight into how cortical networks regulate information processing and energy consumption, offers the avenue for the development of pharmaceutical and medical interventions for improving cognitive function. For example, we will test the prediction that pharmacological augmentation of leptin signalling should improve cortical network processing. Such findings would provide insight as to why obesity, which is associated with leptin insensitivity, can be associated with cognitive dysfunction. This could motivate pharmacological solutions to obesity-related cognitive dysfunction. 2) Policy makers - Our work will provide a basis for studies in humans, which would have the potential to directly impact Obesity and Healthy Eating policies in the UK. 3) Medical professionals, nutritionists, and the general public - In the long-term, by contributing to our understanding of how diet impacts brain activity, ourstudy stands to benefit the quality of life of the general public. Our findings will also have more immediate benefits to medical professionals, nutritionists, and the general public, by increasing awareness of the intimate link between diet and cognitive function. This will be important for informing members of the public about healthy eating and its impact on quality of life.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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