Research Vision

Our aim is to understand how nutrition impacts brain function and energy use. We focus on how dietary manipulations (e.g. calorie restriction, high fat diet, etc) affect the cortex, which we probe in vivo using two-photon imaging and electrophysiology techniques in mice. We additionally carry out dietary manipulations and fMRI work in humans in collaboration with other labs (Farooqi, Fletcher).

We have previously demonstrated that calorie restriction reduces cortical function in mice to save energy, resulting in impaired behavioral function (Padamsey et al., 2022; PMID: 34741806). Mechanistically, these changes depend on diet-induced reductions in the levels of leptin, a hormone that is secreted by adipose tissue in proportion to fat mass. These findings reveal that peripheral metabolic state and brain function are intimately coupled.

Current we have three aims:

• Investigate how obesogenic, high-fat diets impact cortical function and energy use in mice and humans.
• Investigate the role different metabolic hormones, such as leptin and insulin, play in influencing cortical function, including in the context of obesity and type 2 diabetes, which are associated with leptin and insulin resistance.
• Investigate the molecular mechanisms through which metabolic hormones exert their impact on cortical function and energy use.

To address these aims we use a range of techniques. We employ genetic and dietary manipulations in mice, accompanied by detailed investigations of function and energy use in mouse cortex using two-photon calcium and ATP imaging, in vivo and ex vivo patch clamp electrophysiology, and combined laser doppler and haemoglobin spectroscopy in vivo. We complement these techniques with behavioral assays, RNA sequencing, molecular biology approaches, and investigations in primary neuronal culture. For experiments in humans, we employ fMRI and cognitive testing before and after dietary manipulations in collaboration with other labs.

I am always happy to hear from passionate PhD and postdoctoral candidates coming from either a neuroscience or metabolic science background.

Selected publications

*co-corresponding author

Padamsey Z.,* & Rochefort N.L*. (2023). Paying the brain’s energy bill. Current Opinion in Neurobiology. 78(102668). DOI: 10.1016/j.conb.2022.102668 PMID: 36571958

Padamsey Z.,* Katsanevaki D., Dupuy N., & Rochefort N.L*. (2022). Neocortex reduces its coding precision to save energy during food scarcity. Neuron. 110, 280-296. DOI: 10.1016/j.neuron.2021.10.024 PMID: 34741806

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Faulkner A.D. & Burgess C.R. (2022). Metabolic demands, sensory deficits: Tradeoffs in times of scarcity. Neuron. 110(2), 183-184. DOI:10.1016/j.neuron.2021.12.011. PMID: 35051362

Carlsen E.M.M & Rasmussen R.N. (2022). More than meets the eye: The metabolic state of the body shapes visual sensations. Cell Metabolism. 34(1), 9-10. DOI: 10.1016/j.cmet.2021.12.006 PMID: 34986340

Padamsey Z. & Rochefort N.L. (2020) Defying Expectations: How Neurons Compute Prediction Errors in Visual Cortex. Neuron. 6(108), 1016-1019. DOI: 10.1016/j.neuron.2020.12.005 PMID: 33357416

Padamsey Z.*, Tong., R, & Emptage, N.J.* (2019). Optical Quantal Analysis Using Ca²⁺ Indicators: A Robust Method for Assessing Transmitter Release Probability at Excitatory Synapses by Imaging Single Glutamate Release Events. Frontiers in Synaptic Neuroscience. DOI: 10.3389/fnsyn.2019.00005 PMID: 30886576

Vasquez-Lopez S.A., Turcotte R., Koren V., Ploschner M., Padamsey, Z., Booth M.J., Cizmar T., Emptage N.J. (2018). Subcellular spatial resolution achieved for deep-brain imaging in vivo using a minimally invasive multimode fiber. Light: Science & Applications 7(1), 110. DOI: 10.1038/s41377-018-0111-0 PMID: 30588295

Padamsey Z., Foster W., & Emptage, N.J. (2018). Intracellular Ca²⁺ release and synaptic plasticity: a tale of many Ca²⁺ stores. The Neuroscientist. DOI: 10.1177/1073858418785334 PMID: 30014771

Padamsey, Z*., Tong, R., & Emptage, N.J.* (2017). Glutamate is required for depression but not potentiation of long-term presynaptic function. eLife, 6, e29688. DOI: 10.7554/eLife.29688 PMID: 29140248

Padamsey, Z., McGuinness, L., Bardo, S. J., Reinhart, M., Tong, R., Hedegaard, A., Hart, M.L., Emptage, N. J. (2017). Activity- Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines. Neuron, 93(1), 132-146. DOI: 10.1016/j.neuron.2016.11.013 PMID: 27989455 (Previewed in Neuron and Science Signaling; Neuron’s Top 30 articles over 30 years; Faculty 1000 recommendation)