Dr Jon Brown
Dr Jon Brown
G29,
University Walk,
Bristol
BS8 1TD
(See a map)
jon.brown@bristol.ac.uk
Telephone Number (0117) 331 1931
Organisations
Neuronal dysfunction in ageing and disease
Research overview
Research details
Neurones are connected together in complex networks which allow for the storage and retrieval of information. However under certain conditions, these networks are compromised, resulting in deficits in memory and cognitive processing. For example, in Alzheimer’s disease there is significant neuronal loss which results in profound changes to the remaining neuronal network. In contrast in schizophrenia, another condition which results in significant cognitive impairment, there are more subtle alterations in synaptic connectivity between, and within, different brain areas.
The cellular and synaptic mechanisms underlying these changes to neuronal circuitry are not well understood. The goal of our research is to elucidate the relative roles of synaptic dynamics and intrinsic firing properties in neuronal networks and how these are disturbed in disease states. We use electrophysiological techniques (whole-cell and extracellular brain slice recordings) to investigate the intrinsic and synaptic neurophysiological properties of models of disease.
Current projects:
Prefrontal and hippocampal neurophysiology in models of schizophrenia
Subtle changes in neurodevelopment, which result in biochemical, structural, neurophysiological and ultimately behavioural deficits, contribute to the symptoms of schizophrenia. In particular, cortical and limbic regions such as the prefrontal cortex and hippocampus appear to be affected. In collaboration with Pfizer, we are using a range of neurodevelopmental models of schizophrenia to investigate the neurophysiological basis of this condition, using brain slices prepared from the prefrontal cortex and hippocampus.
The neurophysiology of ageing
The normal ageing process results in changes to cognitive function which contributes to the reduced quality of life often experienced by the elderly. However, the neurophysiological bases of these impairments are not understood. In collaboration with Nina Balthasar, Neil Marrion, Richard Apps and Matt Jones, we are studying the effects of ageing on ion channel function and neuroexcitability.
Key words
Electrophysiology, synapse, excitability, networks, hippocampus, prefrontal cortex
Diseases related to this field of research
Schizophrenia, Alzheimer's disease
Processes and functions relevant to this work
Synaptic transmission, Neuronal plasticity,
Research group
Clair Booth, Timothy Church, Mai Kurihara, Charlotte Lawrenson, Sarah Scullion, Alexandra Spittle
Techniques in routine use
Brain slice electrophysiology, calcium imaging
Equipment in routine use
Electrophysiological equipment, Calcium imaging
Collaborations
Andy Randall
Nina Balthasar
Neil Marrion
Richard Apps
Matt Jones
Elek Molnar
Teaching
1st Year Neuroscience PBL
2nd and 3rd Year lectures in neuroanantomy and neurological disorders
Key publications
- Brown, J, Chin, J, Leiser, S, Pangalos, M & Randall, A 2011, ‘Altered intrinsic neuronal excitability and reduced Na+ currents in a mouse model of Alzheimer's disease’. Neurobiology of Aging, vol 32(11)., pp. 2109.e1 - 2109.e14
- Brown, J & Randall, A 2009, ‘Activity-dependent depression of the spike after-depolarization generates long-lasting intrinsic plasticity in hippocampal CA3 pyramidal neurons’. Journal of Physiology, vol 587(6)., pp. 1265 - 1281
- Chelliah, J, Randall, A & Brown, J 2009, ‘Metabotropic glutamate receptor 1 activity generates persistent, N-methyl-D-aspartate receptor-dependent depression of hippocampal pyramidal cell excitability’. European Journal of Neuroscience, vol 29(12)., pp. 2347 - 2362
- Brown, J, Booth, C & Randall, A 2011, ‘Synaptic activation of mGluR1 generates persistent depression of a fast after-depolarizing potential in CA3 pyramidal neurons’. European Journal of Neuroscience, vol 33., pp. 879 - 889
- Brown, J, Davies, C & Randall, A 2007, ‘Synaptic activation of GABAB receptors regulates neuronal network activity and entrainment’. European Journal of Neuroscience, vol 25 (10)., pp. 2982 - 2990
Latest publications
- Brown, J, Hainsworth, AH, Stefani, A & Randall, AD 2013, ‘Whole-cell patch-clamp recording of voltage-sensitive ca(2+) channel currents in single cells: heterologous expression systems and neurones’. Methods in molecular biology (Clifton, N.J.), vol 937., pp. 123-48
- Nowacki, J, Osinga, H, Brown, J, Randall, A & Tsaneva-Atanasova, K 2011, ‘A unified model of CA1/3 pyramidal cells: An investigation into excitability’. Prog Biophys Mol Biol, vol 105(1-2)., pp. 34 - 48
- Nowacki, J, Osinga, H, Brown, J, Randall, A & Tsaneva-Atanasova, K 2011, ‘Sensitivity analysis to explain the excitability in a pyramidal neuron with application to Alzheimer’s disease’. BMC Neuroscience, vol 12., pp. P342
- Booth, C, Nowacki, J, Tsaneva-Atanasova, K, Brown, J & Randall, A 2011, ‘Altered intrinsic properties and resonance in CA1 pyramidal neurons of a transgenic model of tauopathy’. in: Washington, DC: Society for Neuroscience, 2011.
- McMillan, L, Brown, J, Henley, J & Cimarosti, H 2011, ‘Profiles of SUMO and ubiquitin conjugation in an Alzheimer's disease model’. Neuroscience Letters, vol 502(3)., pp. 201 - 208
Full publications list in the University of Bristol publications system