Staff Profile
Dr Faye McLeod
Epilepsy Research Institute UK Fellow
- Telephone: 01912085340
- Personal Website: https://www.researchgate.net/profile/Faye-Mcleod
- Address: Rm MG160
Biosciences Institute
Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
My principal research interests focus on the regulation of synaptic connectivity in health and disease. Efficient synaptic communication is fundamental for every brain process. Dynamic structural and functional changes at the synapse are essential for the formation and refinement of neuronal networks. Importantly, mutations in genes linked to synapse formation and maintenance are associated with diseases of neurodevelopmental origin including epilepsy and autism spectrum disorders (ASD). Consequently, it is essential to understand the mechanisms that modulate the growth and maintenance of synapses in the healthy and diseased brain.
Using a multidisciplinary approach combining cellular biology, live imaging, and electrophysiology techniques in rodent models, I have established how a major class of synaptic modulators, Wnt secreted proteins, function at the synapse and respond to neuronal activity in the developing and mature nervous system. My research has been fundamental in establishing how Wnts contribute to synaptic plasticity and synapse integrity. However, not all findings in rodent model systems can be directly translatable to humans. Therefore, it is crucial to develop and use alternative approaches which can address these fundamental differences. I have established an optimised system which preserves developing and mature human cortical tissue in culture for days to weeks. Utilising this in vitro translational technique, I now aim to study how dysfunction in pre- and postsynaptic proteins cause epilepsy and ASD in humans.
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Articles
- Parrish RR, MacKenzie-Gray Scott C, Jackson-Taylor T, Grundmann A, McLeod F, Codadu NK, Calin A, Alfonsa H, Wykes RC, Voipio J, Trevelyan AJ. Indirect Effects of Halorhodopsin Activation: Potassium Redistribution, Nonspecific Inhibition, and Spreading Depolarization. Journal of Neuroscience 2023, 43(5), 685-692.
- Martin-Flores N, Podpolny M, McLeod F, Workman I, Crawford K, Ivanov D, Leonenko G, Escott-Price V, Salinas PC. Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer’s disease, restores synapse integrity and memory in a disease mouse model. Elife 2023, 12, RP89453.
- Zaaimi B, Turnbull M, Hazra A, Wang Y, Gandara C, McLeod F, McDermott EE, Escobedo-Cousin E, Idil AS, Bailey RG, Tardio S, Patel A, Ponon N, Gausden J, Walsh D, Hutchings F, Kaiser M, Cunningham MO, Clowry GJ, LeBeau FEN, Constandinou TG, Baker SN, Donaldson N, Degenaar P, O'Neill A, Trevelyan AJ, Jackson A. Closed-loop optogenetic control of the dynamics of neural activity in non-human primates. Nature Biomedical Engineering 2023, 7, 559-575.
- McLeod F, Dimtsi A, Marshall AC, Lewis-Smith DJ, Thomas R, Clowry GJ, Trevelyan AJ. Altered synaptic connectivity in an in vitro human model of STXBP1 encephalopathy. Brain 2023, 146(3), 850-857.
- McLeod F, Boyle K, Marzo A, Martin-Flores N, Moe T, Palomer E, Gibb A, Salinas PC. Wnt signalling through nitric oxide synthase promotes the formation of multi-innervated spines. Frontiers in Synaptic Neuroscience 2020, 12, 575863.
- Redlingshöfer L, McLeod F, Chen Y, Camus MD, Burden JJ, Palomer E, Briant K, Dannhauser PN, Salinas PC, Brodsky FM. Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo. PNAS 2020, 117(38), 23527-23538.
- Ferrari M, Bernis M, McLeod F, Podpolny P, Coullery R, Casadei I, Salinas P, Rosso S. Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK. Journal of Cell Science 2018, 131(13), jcs216101.
- McLeod F, Bossio A, Sibilla S, Ciani L, Hannan S, Wilson G, Smart T, Gibb A, Salinas P. Wnt signalling mediates LTP-dependent spine plasticity and AMPAR localization through Frizzled-7 receptors. Cell Reports 2018, 23, 1060-1071.
- McLeod F, Marzo A, Galli S, Salinas P. Evaluation of synapse number in acute hippocampal rodent brain slices. Journal of Visualized Experiments 2017, 128, e56153.
- Marzo A, Galli S, Lopes D, McLeod F, Podpolny M, Segovia-Roldan M, Ciani L, Cacucci F, Gibb A, Salinas P. Reversal of synapse degeneration by restoring Wnt signaling in the adult hippocampus. Current Biology 2016, 26(19), 2551-2561.
- Ciani L, Marzo A, Boyle K, Stamatakou E, Lopes D, Anane D, McLeod F, Rosso S, Gibb A, Salinas P. Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1. Nature Communications 2015, 6, 8302.
- McLeod F, Ganley R, Williams L, Selfridge J, Bird A, Cobb SR. Reduced seizure threshold and altered network oscillatory properties in a mouse model of Rett syndrome. Neuroscience 2013, 231, 195-205.
- Weng SM, McLeod F, Bailey ME, Cobb SR. Synaptic plasticity deficits in an experimental model of rett syndrome: long-term potentiation saturation and its pharmacological reversal. Neuroscience 2011, 180, 314-321.
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Review
- McLeod F, Salinas P. Wnt proteins as modulators of synaptic plasticity. Current Opinion in Neurobiology 2018, 53, 90-95.