School of Medical Sciences


Basal Ganglia Neurophysiology Laboratory

Prinicpal investigators


Summary of research


The main aim of our research is to characterise the mechanisms of neuronal damage in models of Parkinson's disease (PD), and to study the alterations in neuronal activity within the basal ganglia circuit of the brain.

Basal ganglia are deep brain structures formed by several interconnected groups of nerve cells vital for movement. We are particularly interested in the function of two parts of the basal ganglia: the nigro-striatal pathway and the subthalamic nucleus, both strongly affected in PD. Our overall objective is to find new therapeutic strategies based on improved understanding of pathophysiology of affected neurons in these structures.

The main experimental techniques include electrophysiology (e.g., patch-clamping), optogenetics (e.g., channelrhodopsin-assisted circuit mapping; CRACM), electrochemistry (cyclic voltammetry), ion imaging (e.g., calcium imaging) and neuropharmacology. In collaboration with Dr P Kallingappa, we have developed a genetic knockout of the dopamine transporter (DAT) which plays the key role in controlling the action of the neurotransmitter dopamine strongly dysregulated in PD.

Recent and current research projects


  • The role of the dopamine transporter (DAT) and Uptake -2 (Oct and PMAT) in the control of extracellular dopamine levels after genetic inactivation of DAT.
  • Effects of L-DOPA and dopamine on dopaminergic neurons in the nigro-striatal pathway in normal conditions and in models of PD.
  • Optogenetic study of the internal connectivity of neurons in the subthalamic nucleus (STN).
  • The role of endocannabinoids in the function of nigral dopaminergic neurons.
  • Effects of neurotoxins and oxidative stress on dopaminergic and noradrenergic neurons in the Substantia Nigra and the Locus Coeruleus.
  • The mechanism and the role of ‘Spreading Depression’ in damage of nigral dopaminergic neurons.
     

Team members and collaborations


Principal Investigators

Members

Collaborators

Facilities / technology platform

  • Electrophysiology (patch-clamping, intracellular recording with sharp microelectrodes, extracellular recording)
  • Live cell imaging
  • Neuroanatomical techniques
  • Single cell labeling with fluorescent markers
  • Monitoring of ROS production and of mitochondrial membrane potential
  • Microfluorometry (calcium imaging in neurons with fura-2 in brain slices)
  • Measurement of stress-induced cell swelling (tissue impedance and intrinsic optical signals)
  • Immunocytochemistry and Western blotting
  • Pharmacological studies of receptor/channel function
  • Organotypic slice cultures (hippocampus and midbrain)
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