Prof. Kevin Fox
Based at the Neuroscience Group, School of Biosciences
Research Keywords
Synaptic plasticity, experience-dependent plasticity, long-term memory, cortical microcircuitry, critical periods for schizophrenia.
Research Interests and Facilities
We are studying plasticity in an area of the brain that processes tactile information. We record neuronal activity and measure the way sensory processing is modified by experience (experience-dependent plasticity). We can test whether particular proteins are necessary for plasticity and we have found that a major post-synaptic protein known as CAMKII is crucial for plasticity in this area of the cortex. Studies on synaptic plasticity implicate the GluR1 subunit of the AMPA channel and neuronal Nitric oxide synthase, the enzyme that makes nitric oxide are responsible for post- and pres-synaptic components of potentiation respectively.
Plasticity is often impaired in major psychiatric conditions such as autism and schizophrenia. Our studies have shown that the schizophrenia risk gene DISC1 is required during a critical period of cortical development for normal expression of adult plasticity in the barrel cortex and are now studying this in the prefrontal cortex. We are also using forward genetic approaches to discover novel molecules involved in plasticity in collaboration with the NIMH funded Conte Centre for Plasticity and Memory, linking Cardiff University, UCLA and UCSF in a three-way collaboration. So far we have discovered two novel genes for cognitive enhancement. We are using 2-photon spine imaging to understand the relationship between structural spine plasticity and functional plasticity in these cases.
Finally, we need to understand the cortical microcircuit in order to interpret our experience-dependent plasticity studies. We are therefore pursuing optogenetic approaches to manipulate subsets of cortical and thalamic neurons during somatosensation.
Available PhD Projects
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In vivo electrophysiological assay of the role of molecular pathways for cognitive enhancement in cortical plasticity
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In vivo intracellular electrophysiological assay of plasticity in layer V intrinisic burster and regular spiking cells
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2-photon imaging of spine plasticity in mutants lacking specific aspects of synaptic plasticity
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Optogenetic analysis of intracortical pathways for plasticity in barrel cortex
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The role of DISC1 during critical periods of plasticity in barrel cortex and prefrontal cortex.
Publications
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Wright, N, Glazewski, S., Hardingham, N., Phillips, K., Pervolaraki, E. and Fox, K (2008) Laminar analysis of the role played by GluR1 in experience-dependent and synaptic depression in barrel cortex Nature Neuroscience 11(10):1140-2
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Hardingham, N, Wright, N Dachtler, J and Fox, K (2008) Sensory deprivation unmasks a PKA-dependent pathway for cortical synaptic plasticity that operates in parallel with CaMKII Neuron 60(5):861-74 doi:10.1016/j.neuron.2008.10.018
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Wilbrecht, L., Holtmaat, A., Wright, N, Fox, K. and Svoboda, K. (2010) Structural plasticity supports experience-dependent functional plasticity of cortical circuits J. Neuroscience. 30 (14):4927-4932
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Kaneko, M., Cheetham C.E.J., Lee Y.-S., Silva A.J., Stryker M.P. and Fox K. (2010) Constitutively active H-ras accelerates multiple forms of plasticity in developing visual
cortex. Proc. Natl. Acad. Sci. 107(44):19026-31 -
Hardingham, N.R., Dachtler, J., Wright, N.F., Glazewski, S., Blain, E. and Fox, K.(2011) Cortical experience-dependent plasticity acts via GluR1 and a novel NOS1 dependent synaptic mechanism . J. Neurosci. 31(31):11220-11230
Ranson, A., Cheetham, C.E., Fox, K and Sengpiel, F. (2012) Homeostatic plasticity is required for juveline but not adult ocular dominance plasticity. Proc. Natl. Acad. Sci. 109(4)1311-16 doi 10.1073/pnas.1112204109
Jacob, V., Petreanu, L., Wright., N.F., Svoboda, K., and Fox, K. (2012) Regular spiking and instrinsic bursting pyramidal cells show orthogonal forms of experience-dependent plasticity in layer V of barrel cortex. Neuron 73(2):391-404