The research activities of the Neuroscience subject group are aimed at understanding the structure, function and development of the nervous system, and the causes of various neurological disorders. The molecular and cellular mechanisms of learning and memory are one major focus of this subject group. Professors Paul Benjamin, Michael O'Shea and George Kemenes collaborate to produce a systems level understanding of how memories are made in an invertebrate model system. Recent achievements include unravelling the electrical and molecular changes that underlie memory formation in the neuronal network that mediates feeding behaviour in the pond snail, Lymnaea stagnalis (Wan et al., J Neuroscience 2010; Nikitin et al., Current Biology 2008). These changes are conserved across different phylogenetic groups and therefore of direct relevance to how learning occurs in man. The activities of the learning and memory team are complimented by internal collaborations with Dr. Sergie Korneev whose interests include understanding how the gene encoding inducible nitric oxide synthase, an enzyme that regulates the production of the diffusible, gaseous neurotransmitter nitric oxide, is regulated by anti-sense RNA transcripts. The timed regulation of the expression of such transcripts underlies long-term memory formation (Korneev et al., J Neuroscience 2005). Additional and more recent interests of Dr. Korneev include understanding how anti-sense transcripts regulate the differentiation of stem cells into neurons. Dr. Majid Hafezparast also has a keen interest in stem cells and is focused on understanding the genetic and molecular basis of motor neuron disease. He has shown that mutations in cytoplasmic dynein, a protein required for axonal transport, lead to neurodegeneration and has established a link between altered dynein function and the amelioration of disease phenotypes in a mouse model of motor neuron disease (Hafezparast et al., Science 2003; El-Kadi et al, J Biological Chemistry 2010). By taking advantage of novel advances in stem cell biology, Hafezparast's group have recently reprogrammed skin fibroblasts, thereby enabling them to generate millions of motor neurons from mouse models for the study of motor neuron disease. Dr. Kevin Staras is using real time imaging techniques and correlative electron microscopy to study the function of synapses, focusing especially on those in the hippocampus, a region of the central nervous system involved in long-term memory formation. Dr. Staras is studying the feedback mechanisms that control synaptic vesicle release (Branco and Staras, Nature Neuroscience 2009) and has recently discovered the existence of a vesicle superpool, a population of synaptic vesicles that is rapidly shared between the multiple synapses that a single axon can make within the brain (Staras et al., Neuron 2010). Dr. Staras also collaborates actively with members of the subject group working on learning and memory in invertebrates, and is working with Dr. Majid Hafezparast on vesicle trafficking in normal and diseased neurones. Dr. Elizabeth Somerville is a behavioural neuroscientist and has a particular interest in the neural mechanisms of feeding and associated behaviours in mammals (Pulman et al., Pharmacology, Biochemistry & Behavior 2010). Dr. Somerville actively collaborates with members of the School of Psychology.
Hearing Research is a second major focus of the Neuroscience subject group. Professor Corne Kros uses the patch clamp technique to study ribbon synapses and ion channels in sensory hair cells, and is studying the biophysical properties the hair-cell's mechanotransduction channels. He has recently shown that these channels are the route whereby the ototoxic aminoglycoside antibiotics enter and selectively accumulate in hair cells leading to their death (Marcotti et al., J Physiology 2005). Professor Ian Russell uses a variety of electrophysiological techniques and laser interferometry to analyse function of normal and genetically modified mouse cochleae, and is interested in the mechanisms underlying noise- and drug-induced deafness. His research interests also include the mechanisms of echolocation in bats, and the biophysics of insect audition. His recent achievements include discovering an auditory mechanism for species and sexual recognition by mosquitoes (Pennetier et al., Current Biology 2010), and providing further evidence that the electromotile properties of hair cells underlie cochlear amplification (Mellado-Lagarde et al., Nature Neuroscience 2008). Dr. Andrei Lukashkin is a biophyicist and a modeller with an interest in how distortion product otoacoustic emissions, sounds that are generated by the ear, are produced. He has recently provided direct evidence for power amplification in the cochlear (Lukashkin et al., Current Biology 2007). Professor Guy Richardson studies the molecular and cellular basis of hearing and deafness. He is studying and developing mouse models for various forms of human hereditary deafness, and is using cochlear cultures to study damage repair mechanisms in sensory hair cells (Goodyear et al, J Neuroscience 2008). Guy Richardson has ongoing collaborations with both Professors Kros and Russell. Dr. Mark Maconochie is the fifth principal investigator of the Hearing Research team. His interests lie in the mechanisms of inner ear development, with a focus on how signalling through the fibroblast growth factor and insulin growth factor signalling pathways regulate the genesis of auditory and vestibular neurons (Zelarayan et al., Developmental Biology 2007).
The research activities of the Neuroscience Subject Group are funded by programme and project grants from The Wellcome Trust, The MRC and the BBSRC.
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