PhD: Lionel Froux

Properties of the cortico-subthalamic synapse : an optogenetic study

Defended on November 7, 2014

 

Basal ganglia (BG) are a group of subcortical nuclei involved in action selection and in cognitive and motivational aspects of motor behavior. Dopamine is essential for proper functioning of BG. The cortico-subthalamic (cortico-STN) synapse is a glutamatergic (excitatory) synapse involved in signal transmission from cortex to subthalamic nucleus (STN). The cortico-STN synapse is the first synapse in the hyperdirect pathway, one of the three pathways of BG. Even if the cortico-STN pathway is involved in “go-no-go” tasks (stopping of an already started motor act) and in the beneficial effects of the high frequency stimulation of the STN on Parkinsonian symptoms, properties of the cortico-STN synapse are not well described. The lack of data is due, at least in part, to the specific anatomy of the cortico-STN pathway which does not allow the use of standard methods in vitro. The use of optogenetics allowed us to circumvent this issue. By coupling this approach with electrophysiology on brain slices in rodents, we show that dopaminergic D5 receptors stimulation reduces glutamatergic transmission at cortico-STN synapses. We also show that short-term plasticity properties of this synapse reduce the influence of high frequency cortical inputs on the STN. Our findings indicate that optogenetics enables studying the cortico-STN synapse in vitro and contributes to improving our knowledge of the properties of the synapse.

Keywords: basal ganglia, subthalamic nucleus, hyperdirect pathway, dopamine D5 receptor, optogenetics, patch-clamp.  

Publications

Chetrit J, Taupignon A, Froux L, Morin S, Bouali-Benazzouz R, et al. (2013) Inhibiting subthalamic D5 receptor constitutive activity alleviates abnormal electrical activity and reverses motor impairment in a rat model of Parkinson’s disease. J Neurosci 33: 14840-14849.

Lionel Froux, Diana Suarez-Boomgaard, Jérôme Baufreton, Alicia Rivera, Maurice Garret, and Anne Taupignon, Dopamine receptor activity in the subthalamic nucleus. Neuromethods. Acceptée, à paraitre.

Froux L., Lebon-Jego M., Boomgard-Suarez D., Morin S., Rivera A., Miguelez C., Normand E., Baufreton J., Taupignon A., Cortico-subthalamic synapses with low-pass filter properties are negatively controlled by post-synaptic D5 receptors. En préparation.

Jury

  • Laurent Groc
  • Denis Hervé
    DR, INSERM, Paris
  • Paolo Gubellini 
    CR, CNRS, Marseille
    Stéphane Palfi
    PUPH, Université Paris
  • Nicolas Maurice
    CR, CNRS, Marseille
  • José-Luis Lanciego
    PU, Universidad de Navarra, Pampelune, Espagne
  • Anne Taupignon
    MC- PhD, IMN

Directrice de thèse

Anne Taupignon
Maître de conférence – PhD
UFR Sciences pharmaceutiques, Université de Bordeaux
Team : Synaptic and Cellular Dynamics of Neuronal Networks

Last update: 7 November 2014