About Dr. Michael C Ashby

Our 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.Connectivity in a barrel

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).

For further information, please see: http://www.bristol.ac.uk/phys-pharm/people/michael-c-ashby/index.html

5 Selected Publications

Ashby MC., Isaac JT. (2011) Maturation of a recurrent excitatory neocortical circuit by experience-dependent unsilencing of newly-formed dendritic spines. Neuron., 70 (3) :510-21.

Matta JM., Ashby MC., 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., 70 (2) : 339-51.

Daw M., Ashby MC., Isaac JT.(2007) Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex. Nat. Neurosci., 10 (4) :453-61.

Ashby MC., Maier SR., Nishimune A., Henley JM. (2006) Lateral diffusion drives constitutive exchange of AMPA receptors at dendritic spines and is regulated by spine morphology. J. Neurosci., 26 (26) : 7046-55.

Ashby MC., De La Rue S., Ralph GS., Uney J., Collingridge GL., Henley JM. (2004) Removal of AMPARs from synapses is preceded by transient endocytosis of extrasynaptic AMPARs. J. Neurosci., 24 (22) : 5172-6.

Awards, Fellowships, and Honours

2009            Winner of NIH Fellows Award for Research Excellence
2007            Physiological Society Travel Scholarship
2006            Bristol University Young Scientist Travel Grant
2006            Society for Cell Biology Honor Fell Travel Award

Technical Expertise

• Expert in fluorescence microscopy and photostimulation techniques, including over 10 years experience in purchase, use, maintenance, construction and management of laser scanning confocal and multiphoton imaging systems, as well as conventional epifluorescence microscopes

• Highly specialised expertise in the photolysis of caged compounds and photobleaching techniques (FRAP and FLIP)

• Electrophysiology – whole cell voltage and current clamp techniques combined with fluorescence imaging in somatosensory cortex, hippocampus and in pancreatic acinar cells

• Computer programming and mathematical modeling of neuronal connectivity based on graph theory

• Molecular biology – extensive experience of standard plasmid cloning techniques, PCR, in vitro transcription and translation, production of Sindbis pseudovirus

• Biochemistry – Isolation of protein from cells, Western blotting, co-immunoprecipitation, biotinylation

• Cell and tissue culture – acute thalamocortical brain slices, dispersed hippocampal embryonic & postnatal neuronal culture, organotypic hippocampal slice culture, isolation and culture of pancreatic acinar cells

• Gene transfer – chemical transfection procedures, adenoviral and Sindbis virus, nuclear and cytoplasmic microinjection