FUNDAMENTAL RESEARCH

Our working hypothesis is that the identification of dysfunctions of basal ganglia network during development allows understanding the dysfunctions which will appear later in this network during motor pathologies. The main idea is that electrical signals which announce the disease to come, are present very early, perhaps even years before the expression of the disease in humans. We therefore want to identify the early, in utero and postnatal, functional signatures of late (Parkinson’s disease) or less late (Rett syndrome) diseases that affect basal ganglia. This involves recording the developmental, embryonic and postnatal, activities of these networks, in control and pathological situations.

Our previous studies confirm this hypothesis.

In the dorsal striatum, the electrophysiological signatures of the symptomatic period of Parkinson’s disease in the 6-hydroxydopamine mouse model, such as the dysfunction of the striatum interneurons which use GABA (gamma-aminobutyric acid) as the only neurotransmitter (Dehorter et al, 2009), or as a co-neurotransmitter with acetylcholine (Lozovaya et al, 2018) are already present in the asymptomatic period of the disease, 6 to 9 months before the first motor signs, in the genetic model PINK1-/- mouse (Dehorter et al, 2012).

Similarly, The expression of glutamate NMDA receptor subunits is disturbed in dopaminergic neurons of the substantia nigra in the perinatal period, in the PINK1-/- mouse model of Parkinson’s disease (Ferrari et al, 2012, Pearlstein et al, 2015, 2016) and the change of polarity of GABA action in newborn hippocampal neurons is absent in the mouse genetic model (MeCP2) of Rett syndrome (Lozovaya et al, 2019).

PUBLICATIONS

Lozovaya N, Eftekhari S, Cloarec R, Gouty-Colomer LA, Dufour A, Riffault , Billon-Grand M, Pons-Bennaceur A, Oumar N, Burnashev N, Ben-Ari Y, Hammond C.

GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease.

Nature Communications. 2018. 9(1),1-14.

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MICROREVIEW

Lozovaya N, Ben-Ari Y, Hammond C.

Striatal dual cholinergic /GABAergic transmission in Parkinson disease: friends or foes?

Cell Stress, Vol. 2, No. 6, pp. 147 – 149.

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PUBLICATIONS

Gouty-Colomer LA, Michel FJ, Baude A, Lopez-Pauchet C, Dufour A, Cossart R, Hammond C.

Mouse subthalamic nucleus neurons with local axon collaterals.

Journal of Comparative Neurology. 2018. 526(2), 275-284.

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