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, Nardou R, Tyzio R, Chiesa M, Pons-Bennaceur A, Eftekhari S, Bui T-T, Billon-Grand M, Rasero J, Bonifazi P, Guimond D, Gaiarsa  J-L, Ferrari DC & Ben-Ari Y.

Early alterations in a mouse model of Rett syndrome: the GABA developmental shift is abolished at birth.

Sci Rep. 2019; 9: 9276.

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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

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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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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The following publication are based on studies that were made previously at the Inmed (Institut de Neurobiologie de la Méditerranée):

PREVIOUS PUBLICATIONS

Pearlstein E, Michel FJ, Save L, Ferrari DC, Hammond C.

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.

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PREVIOUS PUBLICATIONS

Pearlstein E, Gouty-Colomer LA, Michel FJ, Cloarec R, Hammond C.

Glutamatergic synaptic currents of nigral dopaminergic neurons follow a postnatal developmental sequence

Front Cell Neurosci. 2015 May 29;9:210.

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PREVIOUS PUBLICATIONS

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.

Frontiers in System Neuroscience. 2014. 8,95.

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PUBLICATIONS ANTERIEURES

Dehorter 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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PUBLICATIONS ANTERIEURES

Dehorter N, Lozovaya N, Mdzomba BJ, Michel FJ, Lopez C, Tsintsadze V, Tsintsadze T, Klinkenberg M, Gispert S, Auburger G, Hammond C.

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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PUBLICATIONS ANTERIEURES

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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PUBLICATIONS ANTERIEURES

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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PUBLICATIONS ANTERIEURES

Dehorter 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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ARCHIVES

Mechanisms of High Frequency Cerbral Stimulation

ARCHIVES

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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ARCHIVES

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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ARCHIVES

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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ARCHIVES

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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ARCHIVES

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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ARCHIVES

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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ARCHIVES

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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