We continue to study the synaptic circuitry of neocortex and hippocampus and the pre- and post-synaptic determination and localization of function. Dual/triple intracellular recordings with pharmacology and biocytin-labelling of connected neurones in brain slices detail the properties of synaptic connections and investigate underlying mechanisms. Morphological analyses investigate the specificity with which cells of a particular class in a given layer select target other neurones.

Current Projects :

2008-2013 Mechanisms underlying synapse-specific clustering of GABA_A receptors   Funded by  MRC.  Co-PIs Dr J. Jovanovic, Dr A Mercer and Pr FA Stephenson

On each side of a synapse, proteins cluster into highly specific, complex functional units. Synaptic proteins are highly specialised components. We know something of their structures, their interactions with each other and that subtly different components are used by different types of synapse. What we do not yet understand is how they are selected and inserted at just the right place, or how each combination of components leads to one set of distinctive functional properties. A first requirement  is for two neurones, one on either side of the synapse, is to recognise each other, but  how does it do it? Sheer complexity has, until recently, precluded a deeper understanding. The tools needed to probe further are however, becoming available and with them, new insight into the mechanisms that underlie this precision.

2011-2014 Selective targeting of synapses to specific dendritic locations and their modulation by voltage-gated channels. Funded by the MRC. Co-PIs Dr A Ruiz and Dr M Shah

Evidence for specificity in the properties of synaptic connections is growing, though we know less about the smaller dendritic branches of pyramidal cells and how the properties of postsynaptic dendritic compartments shape individual synaptic inputs and their summation with events from neighbouring synapses. Many different mechanisms contribute to dendritic properties; mechanisms that may be differentially expressed in different pyramidal cells, different dendrites and dendritic compartments. We will test the hypothesis that each class of synaptic input to a given class of postsynaptic cell is distributed over a highly specific region of dendritic space that is homogeneous in its active and passive properties, involves only certain types of dendrites and is at a given electrotonic distance from the soma. 

International Collaboration :

The Human Brain Project  European Commission FET Flagship Programme. Led by Prof Henry Markram and co-directors Prof's Richard Frackowiak and Karlehinz Meier and federating more than 80 European and international research institutions.

The goal of the Human Brain Project is to pull together all our existing knowledge about the human brain and to reconstruct the brain, piece by piece, in supercomputer-based models and simulations. The models offer the prospect of a new understanding of the human brain and its diseases and of completely new computing and robotic technologies. On January 28, the European Commission supported this vision, announcing that it has selected the HBP as one of two projects to be funded through the new FET Flagship Program.