Neuronal Networks Research Group

Sik-Neuronal-networks-picture

 

Group leader: Professor Attila Sik

Overview

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.

Current Projects 

  • 2009-2013 Mechanisms of mesial temporal lobe epilepsy, MRC, co-PI £650,000, Jefferys, Sik
  • 2011-2014 Importance of long-range inhibitory connections in hippocampal network oscillations, MRC, £680,000, PI
  • 2012-2013 Society, Single cell gene delivery in vivo using magnetic nanoparticles, The Royal Society, £6,000, PI
  • 2012-2015 Neural mechanisms of memory updating, BBSRC, £515,663, Lee and Sik
  • 2012-2015 High throughput electrocardiogram recording of zebrafish embryos, British Heart Foundation, New Horizons Grant, £301,840, PI
  • 2013-2015 Novel computational neuronal oscillation to elucidate pathological brain state, The Royal Society, International Exchanges NSFC (China), £12,000, PI
  • 2014-2018 Midbrain dopamine systems and control of bladder function, MRC, £530,960 PIs: Lovick and Sik
  • 2014-2016 Functional and structural changes of brain circuitry in altered oxygen conditions, Marie Curie Fellowship, £309,000

Recent Publications

Staff

Principal Investigators
Professor John Jefferys
Dr Martin Vreugdenhil
Dr Michael Lacey
Dr Emil Toescu

Internal Collaborators
Dr Andrew Powell - School of Clinical and Experimental Medicine, College of Medicine and Dental Sciences

Honorary Staff
Professor John Coote

Postdoctoral Researchers
Dr Andor Magony
Richard Barrett
Jozsef Pal (commences Sept 2014)