Alain Louillot, PhD
Our work involves preclinical modelling of the pathophysiology of schizophrenia. According to contemporary conceptions, schizophrenia involves a functional dysconnection between integrative regions with a neurodevelopmental origin, resulting in dysregulation of mesencephalic dopaminergic (DA) systems. To clarify how DA systems are involved in the pathophysiology of schizophrenia, we are interested in different behavioural and neuropsychopharmacological markers that are altered in schizophrenia. We carried out a transient neonatal functional block using tetrodotoxin (TTX) in various regions, particularly in the prefrontal cortex, which are affected in schizophrenia. Our results show that neonatal inactivation of the prefrontal cortex results in the disappearance of DA responses characteristic of latent inhibition and an increase in reactivity to 2 psychotropic drugs, D-amphetamine and ketamine. These results appear relevant in the context of animal modelling for schizophrenia.
Louilot A., Jeanblanc J., Peterschmitt Y. and Meyer F, Parahippocampal Region-Dopaminergic Neuron Relationships in Latent Inhibition. Dans Latent Inhibition: Cognition, Neuroscience and Applications to Schizophrenia (R.E. Lubow & Ina Weiner, editors) (2010), pp 319-341. Cambridge University Press.
MEYER F. and LOUILOT A., Latent inhibition-related dopaminergic responses in the nucleus accumbens are disrupted following neonatal transient inactivation of the ventral subiculum. Neuropsychopharmacology (2011), 36, 1421-1432.
MEYER F. and LOUILOT A.,Early prefrontal functional blockade in rats results in schizophrenia-related anomalies in behavior and dopamine.Neuropsychopharmacology (2012), 37, 2233-2243.
USUN Y., EYBRARD S., MEYER F. and LOUILOT A., Ketamine increases striatal dopamine release and hyperlocomotion in adult rats after postnatal functional blockade of the prefrontal cortex. Behavioural Brain Research (2013), 256, 229-237.
Didier PINAULT, PhD, HDR, CR Inserm
Transition to psychotic disorders: From pathophysiology to innovative therapy
My goal is to develop, using preclinical models, innovative therapy to treat and prevent neuropsychiatric disorders. It is a conceptually- and data-driven long-term investigation based on the pathophysiological properties of neural networks. EEG combined with multisite cell-to-network exploration are implemented to measure the functional state of Cortico-Thalamo-Cortical systems under physiological, pathological, and therapeutic conditions. CTC systems are the fundamental, oscillating neural substrates of consciousness and attention-related sensorimotor and cognitive processes, and they are suitably electro-responsive to non-invasive, transcranial electrical stimulation.