Dynamic and Pathophysiology of Neuronal Networks (INSERM U667)

Directors : Pr. Jean-Michel DENIAU (Professor paris VI) & Laurent VENANCE (DR2 INSERM)

Physiology and pathophysiology of basal ganglia circuits

Our research is focused on the basal ganglia, a set of subcortical nuclei (striatum, pallidum, subthalamic nuclei and substantia nigra) implicated in the adaptive control of behaviour. Reciprocally connected with the cerebral cortex and the limbic system, the basal ganglia participate to the detection of environmental cues and to the selection of appropriate actions based on motivation and expectancy of reward. Contrary to the prefrontal cortex that acts for changing behavioural strategies, the basal ganglia contribute to the maintenance of successful actions leading to the formation of motor habits.
The pathological dysfunction of basal ganglia leads to major motor and cognitive disorders (Parkinson’s disease, choreic and dystonic involuntary movements, obsessive and compulsive disorders, Tourette’s syndrome, addiction…) for which no fully satisfying treatments are available yet. In a perspective fundamental and therapeutic, our group is particularly focused on the analysis of the functional organization of the basal ganglia network, the mechanisms of synaptic plasticity and the neurochemical processes regulating information processing in this neuronal network.
Our team studies various aspects of the anatomical organization and synaptic interactions underlying the dynamic properties of the basal ganglia network and the changes of these properties in animal models of human pathologies. In the framework of pathophysiological mechanisms, we will be focused on the motor and cognitive impairments related to basal ganglia dysfunction. In a therapeutic perspective, we seek to determine the circuits and the functional mechanisms that are essential to the control of pathological neuronal activities and the modifications by which pharmacological treatments and electrical stimulation normalise these activities. These studies will use anatomical, electrophysiological, neurochemical in vitro and in vivo approaches as well as genetically modified animals. The complementary conceptual and technical expertises of the members of the team together with the collaborations we already established with groups of mathematicians, molecular biologists and pharmaceutical industry allow us to investigate the normal and pathological functions of the BGG at the different levels of complexity of the neuronal network.

The three main programs developed in the lab are the followings:

1) The dynamic and plasticity of the corticostriatal network and its regulation by dopamine. The striatum is the main target structure of dopamine innervation in the basal ganglia. Three main aspects will be examined: the organisation and functional properties of synaptic interactions (chemical and electrical synapses) in the local striatal network, the dopaminergic regulation of corticostriatal synaptic plasticity and the neuron-glia cross-talk.

2) The anatomical organization of the basal ganglia connections.

3) The pathophysiology of motor and cognitive impairments induced by alteration of the dopaminergic transmission and the mechanisms underlying the beneficial effects of the functional therapy by deep brain stimulation. The electrophysiological and neurochemical impact of an alteration of the dopaminergic transmission (hypo et hyper) as well as the electrophysiological effects of high frequency electrical stimulation of the subthalamic nucleus and motor cortex will be studied at different levels of the cortico- basal ganglia loop circuits. In Parkinson’s disease models, we will particularly study the impact of an alteration of the dopaminergic transmission and deep brain stimulation on both the thalamo-cortical network and the integration of cerebellar commands in the motor cortex.

Publications

FINO, E., DENIAU, J.M., VENANCE, L.:
Cell-specific spike-timing-dependent plasticity in GABAergic and cholinergic interneurons in corticostriatal rat brain slices.
J. Physiol, 586.1, 265-282 (2008)

VANDECASTEELE, M., GLOWINSKI, J., DENIAU, JM, VENANCE, L.:
Chemical transmission between dopaminergic neuron pairs
PNAS, 105 n°12, 4904-4909 (2008)

DEGOS, B., DENIAU, JM, LE CAM J., MAILLY P, MAURICE N. :
Evidence for a direct subthalamo-cortical loop circuit in the rat.
Eur J Neurosci, 27, 2599-2610 (2008)

GRAS C., AMILHON B., LEPICARD E., POIREL O., VINATIER J., HERBIN M., DUMAS S., TZAVARA E., WADE M.R., NOMIKOS G., HANOUN N., SAURINI F., KEMEL M.L., GASNIER B., GIROS B., EL MESTIKAWY S. :
The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone.
Nature Neuroscience, 1-9 (2008)

TIERNEY, P.L., THIERRY, A.M., GLOWINSKI, J., DENIAU, J.M., GIOANNI, Y. :
Dopamine modulates temporal dynamics of feedforward inhibition in rat prefrontal cortex in vivo.
Cerebral Cortex, 18, 2251-2262 (2008)

VAN DONGEN Y., MAILLY, P., THIERRY, A.M., GROENEWEGEN H., DENIAU, J.M. :
Three-dimensional organization of dendrites and local axon collaterals of shell and core medium-sized spiny projection neurons of the rat nucleus accumbens.
Brain Structure Funct., 213 (1-2), 129-147 (2008)

ROBIN, K., MAURICE, N., DEGOS, B., DENIAU, JM, MARTINERIE, J., PEZARD, L.
Assessment of bursting activity and interspike intervals variability: A case study for methodological comparison.
J. Neurosci. Methods, (2009)

MEME, W., VANDECASTEELE, M., GIAUME, C., VENANCE, L.
Electrical coupling between hippocampal astrocytes in rat rain slices.
Neuroscience Research, 63, 236-243 (2009)

FINO E, PAILLE V, DENIAU JM, VENANCE L.
Asymmeric spike-timing dependent plasticity of striatal nitric oxide-synthase interneurons.
Neuroscience, 160, 744-754 (2009)

People

Directors :
Jean-Michel DENIAU, Professor Paris VI
jean-michel.deniau@college-de-france.fr

Laurent VENANCE, DR2 INSERM
laurent.venance@college-de-france.fr

Senior researchers :
Yves GIOANNI
yves.gioanni@college-de-france.fr
Marie-louise KEMEL
marie-lou.kemel@college-de-france.fr

Technicians :
Sylvie PÉREZ
Anne-Marie GODEHEU

Post-docs and students:
Vincent PAILLÉ, post-doctorant
Christelle GRAS, post-doctorant
Teresa HERERA-MORRERA, post-doctorant
Luca SALOMON, post-doctorant
Valérie GRAS, doctorant
Clémentine BOSCH, doctorant
Verena ALIANE, doctorant
Hiyui CUI, doctorant

Administrative staff :
Marie-Hélène LEVI
marie-helene.levi@college-de-france.fr
Françoise PENNARUM