Dr Enrico Bracci
The University of Sheffield
Sheffield S10 2TP, UK
Tel: (+44) 0114 222 6593
Fax: (+44) 0114 276 6515
The basal ganglia are subcortical brain nuclei involved in motor control and action selection. The striatum is the main input nucleus of the basal ganglia and converts cortical inputs into an output that is eventually fed back to the cortex through other basal ganglia and thalamic nuclei. This loop is believed to provide permissive or non-permissive signals to cortical assemblies bidding for action. A crucial step to understand this system is to unravel the information processing that takes place in the striatum. We investigate the striatal microcircuits, using single and paired whole-cell recordings as main experimental tools. We have been pursuing three lines of investigation:
|Neuromodulation of striatal networks. We have shown (together with other groups) that striatal interneurons, rather than projection cells, are the main target for extrinsic neuromodulators such as dopamine and serotonin. For instance, we demonstrated that GABAergic interneurons are excited by dopamine and that both cholinergic interneurons and fast-spiking GABAergic interneurons are excited by serotonin. We have also shown that the acute effects of ethanol on the striatum are largely mediated by striatal interneurons. We are currently using transgenic models to investigate how neurotransmitters act on nitric oxide producing interneurons.||Excitatory GABA interactions. We have shown that the interactions between striatal projection neurons, traditionally considered to be inhibitory, can actually be excitatory in certain circumstances. In particular GABAergic synapses can facilitate firing of the postsynaptic cell if appropriately timed with a glutamatergic input. Furthermore, projection neurons can facilitate glutamatergic inputs to other projection neurons through release of neuropeptides. We are currently investigating the micro-architecture of these interactions.|
Presynaptic interactions between striatal neurons. Our experiments have revealed that striatal neurons affect other striatal neurons not only through direct synaptic connections, but also by affecting their synaptic inputs through activation of presynaptic receptors. We have developed a new experimental protocol based on paired recordings and stimulation of afferent fibres, and are able to investigate the extent and time course of these presynaptic interactions in the striatum. In particular, we showed that cholinergic interneuron can depress the glutamatergic inputs of projection neurons and that some projection neurons facilitate glutamate release into neighbouring projection neurons through release of substance P, while other projection neurons inhibit glutamate release by activating presynaptic opioid receptors. We are currently investigation the role of nitric oxide in mediating presynaptic interactions. We are also collaborating with Kevin Gurney and Paul Overton to make sense of how these presynaptic interactions affect the dynamics of the striatal network and its ability to carry out action selection.
- MRC "How do nitrergic interneurons control corticostriatal communication?". E. Bracci. (2013) £428K.
- Wellcome Trust “Presynaptic interactions in the striatum investigated with paired recordings”. E. Bracci. (2009) £345K.
- Royal Society “Exploring the functional topography of somatosensory corticostriatal projections.” E. Bracci (2006). £14K.
- Wellcome Trust “The architecture of the GABAergic circuits in the striatum and its dopaminergic modulation”. E. Bracci (2004). £324K
- Royal Society “Epileptiform activity in the striatum”. E. Bracci (2003) £15K.
- Ritchie Smith (PhD Student)
- Christopher Logie (PhD Student)
- Rasha El Ghaba (PhD Student)
A list of key publications can be found below. For a full list of publications please click here
- Logie C, Bagetta V & Bracci E (2013) Presynaptic control of corticostriatal synapses by endogenous GABA. Journal of Neuroscience, 33(39), 15425-15431.
- Blomeley CP & Bracci E (2011) Opioidergic interactions between striatal projection neurons.. J Neurosci, 31(38), 13346-13356.
- Blomeley CP, Cains S, Smith R & Bracci E (2011) Ethanol affects striatal interneurons directly and projection neurons through a reduction in cholinergic tone.. Neuropsychopharmacology, 36(5), 1033-1046.
- Blomeley CP, Kehoe LA & Bracci E (2009) Substance P mediates excitatory interactions between striatal projection neurons.. J Neurosci, 29(15), 4953-4963.
- Pakhotin P & Bracci E (2007) Cholinergic interneurons control the excitatory input to the striatum.. J Neurosci, 27(2), 391-400.