About Dr. Olivier Manzoni

Work in the laboratory focuses on the role of hub proteins/supramolecular complexes in the etiology of neuropsychiatric diseases. Our research strategy is to analyze the mechanisms and the functions of synaptic signalosome in neuronal integration in pathophysiological conditions using animal model of neuropsychiatric diseases (depression, mental retardation, autism, drug addiction).

Major neuropsychiatric disorders including mental retardation, autism, schizophrenia, depression and addiction are accompanied by alterations of the very substrates of the neural code.

At the synaptic level, the neural code is processed by postsynaptic molecular machines made of macromolecular complexes complexes of interacting proteins organized into a scale-free network.

The “small world” nature of multiprotein complexes implies highly organized interconnected structures where changes in one protein can readily alter the functions of many others. Therefore, proteins with the higher number of connections, the so-called “hub proteins” are of particular significance to network integrity and synaptic plasticity.

Synaptic plasticity underlies dynamic changes in neural networks that are triggered by environmental stimuli and individual experiences. Such dynamic changes are fundamental to normal brain functions. From early development to adulthood, synaptic plasticity is necessary to learn new abilities, form new memories and generate new adaptive behaviors.

Aberrant synaptic transmission and/or plasticity participate to the etiology of neuropsychiatric diseases: disruption of a molecular cog of the synaptic machine causes or result in deficits in synaptic plasticity and leads to abnormal information processing.

The concept that major brain diseases are either caused by or result in deficits in synaptic plasticity is supported by the observation that most synaptic hub proteins (e.g. NMDAR, mGluR1/5) are involved in psychiatric and/or neurodegenerative disease.

Most neuropsychiatric disorders are accompanied by significant social, emotional and cognitive problems. Surprisingly, the neuronal substrates of emotional perturbation are seldom studied in the context of these pathologies.

Specific Projects

Regulation of mood and emotion is critical for mental health. Major neuropsychiatric disorders including mental retardation, autism, schizophrenia, depression and addiction are accompanied by significant social, emotional and cognitive problems. Surprisingly, the neuronal substrates of emotional perturbation are seldom studied in the context of these pathologies. In neuropsychiatric diseases, disruption of a molecular cog of the synaptic machine causes or result in deficits in synaptic plasticity (SP) and leads to abnormal information processing.

Our specific goal is to unravel synaptic dysfunctions and propose new therapeutic venues for synaptopathies. Our integrated approach is composed of three lines of research:
-Audit of physiological synaptic networks
-Identification of synaptopathies in neuropsychiatric diseases
-Rescue.

For more information, please go to: http://www.inmed.fr/en/en-physiopathologie-de-la-plasticite-synaptique

A full publication record can be found here.