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Dr Michael Ashby
Dr Michael Ashby
Area of research
How early life experience guides the formation of synapses and circuits in the neocortex
My research addresses the development of brain circuitry early in life, when anatomical and synaptic plasticity coordinate dramatically to produce functional circuits in the mammalian cortex. Using high resolution optical stimulation and recording combined with molecular, genetic and electrophysiological methods, I aim to define how neonatal sensory experience influences the normal and pathological cortical circuit development that underlies lifelong brain function.
This is an example of the type of connectivity map generated using 2-photon stimulation and patch clamp electrophysiology to detect and measure synaptic connections. Each sphere represents a neuron inside the barrel structure that is found in the sensory cortex. The green neuron was recorded during the experiment and is shown here with all its dendrites. The other neurons were stimulated during the experiment to find those that make synaptic connections with the recorded cell. Only a small proportion of cells, those shown in colour, are connected. This type of map tells us about rates of connectivity, the properties of those synapses and the geometric relationship between connected cells. Comparing these maps at different stages of early postnatal development allows us to understand the processes involved in the formation of circuitry in the sensory cortex (Ashby & Isaac 2011, Neuron 70:510-521).
Activities / Findings
- Sensory experience controls circuit maturation by determining synaptic glutamate receptor content
- Local excitatory microcircuit in the barrel cortex have a highly recurrent, 'small-world' architecture
- There is a dissociation between anatomical and functional maturation of dendritic spines that is controlled by sensory experience
- Development of a 2-photon-based optical stimulation method for circuit mapping at the single cell level
MBChB Level 2
Neurons, glia and neural circuits
Pharmacology and treatment of dementia
Treatment of movement disorders
- Jackson, J, Witton, J, Johnson, JD, Ahmed, Z, Ward, M, Randall, AD, Hutton, ML, Isaac, JTR, O'Neill, MJ & Ashby, MC, 2017, Altered synapse stability in the early stages of tauopathy. Cell Reports, vol 18., pp. 3063-3068
- Ashby, M & Isaac, J, 2011, Maturation of a recurrent excitatory neocortical circuit by experience-dependent unsilencing of newly-formed dendritic spines. Neuron, vol 70., pp. 510 - 521
- Ashby, M, Maier, S, Nishimune, A & Henley, J, 2006, Lateral diffusion drives constitutive exchange of AMPA receptors at dendritic spines and is regulated by spine morphology. Journal of Neuroscience, vol 26 (26)., pp. 7046 - 7055
Read more >
- Tigaret, CM, Olivo, V, Sadowski, JHL, Ashby, MC & Mellor, JR, 2016, Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity. Nature Communications, vol 7.
- Wilkinson, KA, Ashby, MC & Henley, JM, 2014, Validity of pHluorin-tagged GluA2 as a reporter for AMPA receptor surface expression and endocytosis. Proceedings of the National Academy of Sciences of the United States of America, vol 111., pp. E304
- González-González, I, Jaskolski, F, Goldberg, Y, Ashby, M & Henley, J, 2012, Chapter six - Measuring membrane protein dynamics in neurons using fluorescence recovery after photobleach. Methods in Enzymology, vol 504., pp. 127 - 146
- Matta, J, Ashby, M, Sanz-Clemente, A, Roche, K & Isaac, J, 2011, mGluR5 and NMDA receptors drive the experience- and activity-dependent NMDA receptor NR2B to NR2A subunit switch. Neuron, vol 70., pp. 339 - 351
- Ashby, M, Daw, M & Isaac, J, 2008, AMPA Receptors. in: RW Gereau, GT Swanson (eds) The Glutamate Receptors. Humana Press, pp. 1 - 44
- Daw, M, Ashby, M & Isaac, J, 2007, Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex. Nature Neuroscience, vol 10(4)., pp. 453 - 461
- Isaac, J, Ashby, M & Mcbain, C, 2007, The Role of the GluR2 Subunit in AMPA Receptor Function and Synaptic Plasticity. Neuron, vol 54., pp. 859 - 871
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