- Unit7 Mar 2014
Unit director Peter Somogyi receives Honorary Doctorate from the University of Zurich. Prof Dr Michael Hengartner the President greeted Peter as the latest Honorary Doctor of the prestigious University of Zurich. The title will be bestowed on him in a ceremony Dies Academicus on the 26th of April. Peter collaborated with world leading neuroscientists the late Peter Streit and the current head of the Department of Pharmacology and Toxicology Prof Jean-Marc Fritschy. Prof Hengartner wrote “I take great pleasure in informing you of the decision of the Faculty of Medicine to award you an honorary doctorate. This high distinction recognizes and honors your outstanding achievements in research on neuronal circuits in the cerebral cortex “. In his acceptance letter Peter replied: “I am delighted to learn that the Faculty of Medicine recommended the awarding of an honorary doctorate to me of you esteemed University, which I hold in the highest regard”.
- Unit4 Mar 2014
Marco Bocchio wins the Gotch Memorial Prize 2013 for the best DPhil Transfer Status report of an Oxford graduate student in the field of Physiology. The award is £1,000.
The title of his transfer report is "Serotonergic neuromodulation of the mouse amygdala".
Recent studies in animals and humans have proven that serotonergic neurotransmission in the Basolateral Amygdala (BLA) is a critical component for the regulation of emotional behaviour and psychiatric disorders. However, the effects of serotonergic transmission on BLA neuronal network are currently poorly understood.
The report investigates the effect of serotonin (5-Hydroxytriptamine, 5-HT) on:
1) GABAergic interneurons (INs) innervating Principal Neurons (PNs) of the Basal Amygdala in mice overexpressing the serotonin transporter (5-HTT OE), an animal model displaying reduced anxiety; and 2) neurons of the Lateral Amygdala (LA) expressing neuronal nitric oxide synthase (nNOS), a cell type displaying Low-threshold Spiking (LTS) features.
The experiments described hereby show that overexpression of 5-HTT leads to a deficit in GABAergic INs activation in the Basal Amygdala (BA), namely reduced inhibition onto PN.
Additionally, 5-HT elicits a switch from tonic firing to burst firing of nNOS+ neurons of the LA, potentially driven by hyperpolarization. This contrasts with the known depolarizing action of 5-HT on other GABAergic populations investigated so far. The description of the anatomical aspects and electrophysiological responses of nNOS+ neurons is also addressed. Results suggest that this cell population is likely to be formed by long-range GABAergic projection neurons, the presence of which has never been reported in the BLA.
- Unit7 Feb 2014
Members of the Magill and Bolam Basal Ganglia Labs attended the Gordon Research Conference on “Basal Ganglia Cells and Circuits in Health and Disease”, which was held in Ventura, California, from the 2nd – 7th February 2014. This is a new meeting that brings together leading groups to discuss the latest advances in the field of basal ganglia research, with a view to promoting discussion of unpublished data and fostering cross-cutting collaborations. Further emphasis was placed on showcasing developments that have translational significance. The meeting consisted of daily symposia and poster sessions.
The latest discoveries from the Unit’s Basal Ganglia Labs were well represented through symposium talks by Paul Bolam, Peter Magill and Juan Mena-Segovia.
Other lab members presented the following posters:
Daniel Dautan, Icnelia Huerta-Ocampo, Ilana Witten, Karl Deisseroth, Paul Bolam, Todor Gerdjikov & Juan Mena-Segovia. “A major external source of cholinergic innervation of the striatum and nucleus accumbens originates in the brainstem”
Albert Souza, Ilana B. Witten, Karl Deisseroth, J. Paul Bolam, Todor V Gerdjikov & Juan Mena-Segovia. “Dopamine neurons of the ventral tegmental area are differentially modulated by brainstem cholinergic pathways"
Paul D. Dodson, Ian C. Duguid, J. Paul Bolam & Peter J. Magill. “Distinct firing patterns of prototypic and arkypallidal neurons of the GPe during movement”
Farid Garas, Andrew Sharott & Peter J. Magill. “Molecular markers of novel populations of striatal interneurons”
Kouichi C. Nakamura, Andrew Sharott, Nicolas Mallet & Peter J. Magill. “Neuronal activity in the motor thalamus of dopamine-intact and Parkinsonian rats"
Federica Vinciati, Andrew Sharott, Kouichi C. Nakamura & Peter J. Magill. “In vivo electrophysiological properties of neurochemically-identified striatal neurons in dopamine-intact and Parkinsonian rats”
- Unit23 Jan 2014
The hippocampus contains more than 20 types of inhibitory interneurons that express different proteins and impinge on different regions of pyramidal cells to regulate spatiotemporal integration of EPSPs and define temporal windows for spiking. Neurogliaform cells (NGFCs) form synapses on the distal tufts of pyramidal cell apical dendrites alongside excitatory inputs from the entorhinal cortex. NGFCs express neuronal nitric oxide synthase (nNOS), are often synaptically coupled, and fire during theta oscillations . Li et al. published a “featured article” in the Journal of Neuroscience (34(4):1280-1292, 2014) reporting a novel physiological action mediated by this interneuron type. They found that when theta-associated activity patterns were evoked in NGFCs in hippocampal slices of rat or mouse, the cells showed a transient reduction in unitary IPSP amplitude. This “firing-induced suppression of inhibition” (FSI) required back-propagation of action potentials, calcium influx through L-type calcium channels, nNOS activity, and activation of NO-sensitive guanylyl cyclase (NO-sGC) receptors, which are present on presynaptic terminals. FSI also indirectly increased the amplitude of EPSPs. Thus FSI may enhance spatial and temporal summation of excitatory inputs to NGFCs, regulating their inhibition of pyramidal cells. More in general, this work demonstrates: 1) retrograde signaling initiated by “in vivo firing pattern”, 2) interneuron back-propagation detected with fast time resolution voltage imaging, and 3) physiological role for nNOS expressed by specific interneuron types.
- Unit6 Jan 2014
Mark is a current student on the MSc Neuroscience course, joining the Bolam group under the supervision of Dr Mena-Segovia for 3 months. His project aims to characterise the physiological effects of cholinergic transmission in the basal ganglia using juxtacellular recordings and neuroanatomical techniques. Mark received his BSc in Pharmacology from Newcastle University, where he studied the effects of early-life stress on gamma oscillations in the basolateral amygdala.Related Group :
- Unit6 Jan 2014
Miss Fahrat is visiting the laboratory from January until July 2014 to study GABAergic inhibitory interneurons in the hippocampus. For the visit, she was awarded a stipend from Higher Education Commission of Pakistan. Her visit is part of her Ph.D. in National University of Sciences and Technology in Islamabad, Pakistan.
- Unit18 Dec 2013
The Unit held its Winter Science Day on Wednesday 18th December 2013. 67 Unit members and visitors attended, including guest speakers Prof. John Jefferies and Prof. Matthew Walker. There were 12 oral presentations and 9 posters describing on-going projects and plans for the future. This Science Day was also a celebration of both the Unit's 25th year, and the Centenary of the MRC.
- Unit29 Oct 2013
Use of stem cells for dopamine cell replacement in Parkinson's disease.
Anders gave an inspiring lecture plotting the history of cell transplantation studies. He took us from the very beginnings of the field in the seventies and eighties describing his early studies in animal models, through the first clinical trials in Parkinson's disease and more recent data on the use of stem cell and strategies for the conversion of stem cell into dopamine neurons. We all look forward to the culmination of this work when trials of stem cell-derived dopamine neurons can be used in the treatment of Parkinson's disease.
The Lecture each year celebrates the vision of the previous Chair of Pharmacology and founding Director of the Unit, Prof. A. David Smith, currently Honorary Associate Director and Emeritus Professor, and the successful conclusion of the last quinquennial scientific review of the Unit.
To commemorate the lecture Prof. Björklund received a laser-engraved cherry-wood plaque, designed by Unit Artist, Ben Micklem, illustrating aspects of Anatomical Neuropharmacology at Oxford from molecules to the brain.
- Unit21 Oct 2013
Tim Viney and his colleagues established that GABAergic axo-axonic interneurons, which only innervate the axon initial segments of pyramidal cells, are inhibited in the CA3 area of the hippocampus during so-called sharp wave-ripple events (SWRs). These SWRs represent population bursts of pyramidal cells and are initiated in the CA3 area. Axo-axonic cells, which activate GABA-A receptors, were previously discovered by members of the MRC Unit. Pyramidal cells fire sequentially during active behaviour and these sequences are replayed in a time-compressed manner during slow wave sleep and awake consummatory behaviour; at times when hippocampo-neocortical readout and memory consolidation take place. The paper also reports a selective GABAergic input to axo-axonic cells from the medial septum, and that some GABAergic medial septal neurons are activated during SWRs. The authors hypothesize that the silencing of the axo-axonic cells during SWRs enables the pyramidal cells to discharge and replay the sequences of action potentials formed by connections when the animal was awake.
The discovery that axo-axonic cells are silenced during the replay of memory traces reveals the cellular mechanism of how withdrawal of inhibition at the strategic subcellular location, the axon initial segment of pyramidal cells, assists in memory consolidation. The results contribute to defining the chronocircuit of the brain, which is the mission of the Unit.
Viney, T.J.*, Lasztóczi, B.*, Katona, L.*, Crump, M.G.*, Tukker, J.J., Klausberger, T. & Somogyi, P. (2013) Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells in vivo. Nat. Neurosci. doi:10.1038/nn.3550.
*equal first authors.
- Unit21 Oct 2013
Ms Maysa Falah has joined the Lamsa laboratory as a research student. Maysa graduated from the University of Science and Technology in Jordan and received her MSc degree in the Department of Pharmacology, University of Oxford under supervision of Professor Trevor Sharp. During her Master’s Maysa studied mechanisms of depression in Parkinson ’s disease. In her thesis, Maysa investigates excitatoxic role of NMDAR hyperfunction in human hippocampal sclerosis. Her thesis project (started in 2013) is a collaboration between The Nuffield Department of Clinical Neurosciences and the Department of Pharmacology, University of Oxford, and is co-supervised by Dr. Arjune Sen and Dr. Karri Lamsa.