The mechanisms behind normal and abnormal brain functions are the consequence of interaction between neurons and neurons and glial cells. The goal is to understand the structure and function of the networks in health and diseases.
Our research group
In the laboratory we combine a wide array of anatomical and electrophysiology methods with molecular biology tools and behavioural analysis to investigate the structural-functional relationship of neuronal networks in the cortex, hippocampus, and in several subcortical structures. The level of analysis spans from cell cultures, through slice cultures and anaesthetised animals to freely moving animals. We investigate the composition of hippocampal and cortical network focusing mainly inhibitory neurons and the mechanism that renders the healthy network to epileptic. Our other interest is the effect of oxygen change on brain activity, and the distribution of various ions in the brain in normal and abnormal condition. We also interested in the underlying neuronal mechanism of social behaviour.
Cognitive function depends on precise network dynamics, including those in the “gamma band” (about 40 Hz). Cognition is impaired with normal ageing. We have shown impaired gamma oscillations in old brains. We also have shown that ageing is associated with impaired mitochondrial function in the old neurons, which, with altered Ca2+ homeostasis, contributes to decreased neuronal homeostatic reserve, and increased neuronal vulnerability and risk of neurodegeneration.
Cognition also is impaired in X-linked mental retardation, where we found disruption of synaptic transmission at the frequencies of gamma-band oscillations.
Cognitive functions are also altered in schizophrenia. We use animal models like intrauterine MAM and acute ketamine or PCP to induce psychotic behaviours where we aim to link changes in oscillations to changes in perception and other aspects of cognition. In vitro studies are used to understand underlying mechanisms.
Importance of long-range inhibitory connections in hippocampal network oscillations (Sik, Medical Research Council)
Single cell gene delivery in vivo using magnetic nanoparticles (Sik and Dobson (University of Florida, USA) Royal Society)
High throughput electrocardiogram recording of zebrafish embryos (Sik, Muller, Egginton and Tarte, British Heart Foundation)
Midbrain dopamine systems and control of bladder function (Lovick and Sik, Medical Research Council)
Ward KC, Khattak HZ, Richardson L, Lee JL and Vreugdenhil M (2013) NMDA receptor antagonists distort visual grouping in rats performing a modified two-choice visual discrimination task. Psychopharmacology (Berl) [Epub ahead of print]
Kovács K, Basu K, Rouiller I and Sík A (2013) Regional differences in the expression of K+-Cl– 2 cotransporter in the developing rat neocortex, Brain structure and function [in press]
Powell AD, Gill KK, Saintot PP, Jiruska P, Chelly J, Billuart P and Jefferys JGR (2012) Rapid reversal of impaired inhibitory and excitatory transmission but not spine dysgenesis in a mouse model of mental retardation. J Physiol 590:763-76
Lu CB, Jefferys JGR, Toescu EC and Vreugdenhil M (2011) In vitro hippocampal gamma oscillation power as an index of in vivo CA3 gamma oscillation strength and spatial reference memory. Neurobiol Learning & Memory 95:221-230
Kroeger D, Tamburri A, Amzica F and Sík A (2010) Activity dependent layer-specific changes in the extracellular chloride concentration and chloride driving force in the rat hippocampus. J Neurophysiology 103:1905-1914
Professor John Jefferys
Dr Martin Vreugdenhil
Dr Michael Lacey
Dr Emil Toescu
Dr Andrew Powell - School of Clinical and Experimental Medicine, College of Medicine and Dental Sciences
Professor John Coote
Dr Andor Magony