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).
GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease.
Nature Communications. 2018. 9(1),1-14.
Plus d'informationsParkinson disease: a tale of three neurotransmitters.
Atlas of Science.
Plus d'informationsLozovaya 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.
Plus d'informationsGouty-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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The following publication are based on studies that were made previously at the Inmed (Institut de Neurobiologie de la Méditerranée):
Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1-/- Mouse Model of Parkinson’s Disease.
Front Cell Neurosci. 2016 Jun 23;10:168.
Plus d'informationsGlutamatergic synaptic currents of nigral dopaminergic neurons follow a postnatal developmental sequence
Front Cell Neurosci. 2015 May 29;9:210.
Plus d'informationsCarron R, Filipchuck A, Nardou R, Singh A, Michel FJ, Humphries MD, Hammond C.
Early hypersynchrony in juvenile PINK1 -/- motor cortex is rescued by antidromic stimulation.
Frontiers in System Neuroscience. 2014. 8,95.
Plus d'informationsDehorter N, Hammond C.
Giant GABAA receptor mediated currents in the striatum, a common signature of Parkinson’s disease in pharmacological and genetic rodent models
Basal Ganglia 2014 Apr :197-201.
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(article en anglais)
Subthalamic lesion or levodopa treatment rescues giant GABAergic currents of PINK1-deficient striatum.
J Neurosci. 2012 Dec 12;32(50):18047-53.
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(article en anglais)
Dehorter N, Vinay L, Hammond C and Ben-Ari Y.
Timing of developmental sequences in different brain structures: physiological and pathological implications
Eur J Neurosci. 2012 Jun;35(12):1846-56.
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(article en anglais)
Ferrari DC, Mdzomba BJ, Dehorter N, Lopez C, Michel FJ, libersat F, Hammond C.
Midbrain dopaminergic neurons generate calcium and sodium currents and release dopamine in the striatum of pups.
Front Cell Neurosci. 2012 Mar 8;6:7.
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Plus d'informationsDehorter N, Guigoni C, Lopez C, Hirsch J, EusebioA, Ben-Ari Y, Hammond C.
Dopamine-deprived striatal GABAergicinterneurons burst and generate repetitive gigantic IPSCs in medium spiny neurons.
J Neurosci. 2009 Jun 17;29(24):7776-87.
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(article en anglais)
Carron R, Filipchuck A, Nardou R, Singh A, Michel FJ, Humphries MD, Hammond C.
Early hypersynchrony in juvenile PINK1−/− motor cortex is rescued by antidromic stimulation
Front Syst Neurosci. 2014; 8: 95.
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Carron R, Chaillet A, Filipchuck A, Pasillas-Lepine W, Hammond C.
Closing the loop of deep brain stimulation.
Front Syst Neurosci. 2013 Dec 20;7:112.
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Carron R, Chabardes S, Hammond C.
Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts
Neurochirurgie. 2012 Aug;58(4):209-17
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Ammari R, Bioulac B, Garcia L, Hammond C.
The Subthalamic Nucleus becomes a Generator of Bursts in the Dopamine-Depleted State. Its High Frequency Stimulation Dramatically Weakens Transmission to the Globus Pallidus
Front Syst Neurosci. 2011; 5: 43.
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Hammond C, Ammari R, Bioulac B, Garcia L.
Latest View on the Mechanism of Action of Deep Brain Stimulation
Mov Disord. 2008 Nov 15;23(15):2111-21.
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Garcia L, D’Alessandro G, Bioulac B, Hammond C.
High-frequency stimulation in Parkinson’s disease: more or less?
Trends Neurosci. 2005 Apr;28(4):209-16.
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Garcia L, Audin J, D’Alessandro G, Bioulac B, Hammond C.
Dual Effect of High-Frequency Stimulation on Subthalamic Neuron Activity
J Neurosci. 2003 Sep 24;23(25):8743-51.
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