MRC Grant Success for Enrico Bracci

We are pleased to announce that Dr Enrico Bracci has won a grant from MRC with a RC contribution of  £428,336.05.  This grant will employ one full time PDRA and one full time technician on the grant.  Please see the abstract below:

How do nitrergic interneurons control corticostriatal communication?

The basal ganglia are a group of brain nuclei essential for motor control. The striatum is the largest and most complex of these nuclei, and plays an essential role in the basal ganglia communication with other brain areas such as the cerebral cortex and the thalamus. When things go wrong in the striatum, devastating neurological consequences emerge; Parkinson's disease and Huntington's disease are two examples of striatal  malfunctioning. In Parkinson's disease patients find it very hard to execute movement, while in Huntington's disease patients cannot suppress unwanted movements. The compulsive elements of drug addiction are also thought to result from aberrant memories stored in the striatum. Therefore, understanding the way in which the striatum operates is essential to understand how motor control is accomplished in healthy people and why things go wrong in many neurological diseases. The striatum comprises tens of thousands of neurons interconnected in a complex manner. If we want to understand the way in which this nucleus carries out its computations, we have to understand first how striatal neurons process information coming from the cerebral cortex. This communication takes place through chemicals known as neurotransmitters. In the last twenty years it has become clear that nitric oxide acts as a neurotransmitter in the brain and in the striatum in particular. We know that nitric oxide is necessary for the normal operation of the striatum, and in particular for some forms of long-term synaptic plasticity, which is the cellular basis of motor learning. There is also evidence that nitric oxide signalling is altered in Parkinson's disease. However, how nitric oxide produced by the striatum controls the flow of information reaching the striatum from the cerebral cortex remains unclear. The main obstacle to obtaing this information has been that nitric oxide is only produced by a small number of specialised neurons that are difficult to identify and record from. This has now changed thanks to the introduction of transgenic mice in which the nitric oxide producing neurons of the striatum express a green fluorescent protein. Using these mice, it is possible to visually identify these neurons and study their interactions with other neurons. We will investigate these interactions using a sophisticated electrophysiological technique known as "paired recordings" in which two neurons are simultaneously monitored and stimulated electrically, so that their communication becomes apparent. We will also use other transgenic mice in which the nitrergic interneurons can be stimulated with flashes of light to investigate what happens when many of these nitrergic interneruons are activated simultaneously. These experiments will significantly improve our knowledge of the striatum and therefore provide new tools to understand and counteract the symptoms of neurological diseases caused by its malfunctioning.