Institute of Neuroscience

Staff Profile

Dr Faye McLeod

Research Associate

Research

My principle research interests focus on the regulation of synaptic connectivity in health and disease. The brain is shaped by both its inherited genetic code and the environment. The latter leads to neuronal activity induced changes at the synapse essential for brain development and maturation. The ability of synapses to dynamically respond to various stimuli results in long lasting structural and functional modifications. This is the fundamental basis of synaptic plasticity and the cellular correlate of learning and memory. Significant progress has been made in understanding the intracellular pathways underlying this process. Nonetheless, the role that synaptic modulators play is still poorly understood.

Wnt secreted proteins

Using a multidisciplinary approach combining cellular biology, live imaging and electrophysiology techniques, I have established how a major class of synaptic modulators, Wnt secreted proteins, function at the synapse and respond to neuronal activity. Pre-synaptically, I show that Wnts contribute to the activity-dependent release of glutamate. Post-synaptically, through Frizzled 7 receptors, Wnts increase spine growth and AMPAR recruitment during synaptic plasticity. I identify that Wnt7a mediates these effects, is regulated by neuronal activity and is required for activity-mediated multiple innervation of spines. Furthermore, I have demonstrated an imperative role for Wnts in the maintenance of synapses in the adult hippocampus. Collectively, my research has been fundamental in establishing how Wnts contribute to synaptic plasticity and synapse integrity.

Current research

I am now developing an optimised system which preserves developing and mature human cortical tissue in culture for days to weeks. Utilising this technique to study how synaptic structure and function are affected upon regulation of the Wnt pathway could provide a valuable translational model for multiple neurological diseases including neurodevelopmental disorders and epilepsy. This current work is also funded by CANDO ("Controlling Abnormal Network Dynamics with Optogenetics", see http://www.cando.ac.uk/), a project aiming to develop a cortical implant for optogenetic neural control of focal epilepsy.

 

Publications

  • Ferrari M, Bernis M, McLeod F, Podpolny P, Coullery R, Casadei I, Salinas P, Rosso S. Frizzled-7, as a Wnt7b receptor, modulates dendrite development of hippocampal neurons through Ca2+/Calmodulin-dependent protein kinase II. Journal of Cell Science 2018, 131.
  • McLeod F, Salinas P. Wnt proteins as modulators of synaptic plasticity. Current Opinion in Neurobiology 2018, 53, 90-95.
  • 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. J Vis Exp 2017, 128.
  • 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.
  • 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.