Experience-dependent plasticity modulating cognitive deficits in schizophrenia

We have demonstrated that onset and progression of Huntington’s disease, an autosomal dominant disorder previously considered the epitome of genetic determinism, as well as other brain disorders, can be beneficially modulated by environmental stimulation. Environmental factors also modulate cortical development and several pathways that are key to the genesis of psychiatric symptoms.

Cognitive dysfunction appears as a core feature of psychiatric disorders such as schizophrenia. There is a need for better understanding of cognitive impairments in rodent models of psychiatric disorders in order to elucidate the pathogenic mechanisms and to develop more effective therapies.

We propose that an intra-neuronal signaling pathway, which includes specific glutamate receptors, as well as brain-derived neurotrophic factor (BDNF), is required for experience-dependent maturation and plasticity of inter-neuronal circuitry in the neocortex and hippocampus.

We will carry out behavioural, cellular and molecular analysis of wild-type and gene-edited mice, following specific environmental manipulations, to establish the effect of environmental modulators on these molecular mediators in cortical plasticity and associated aspects of behaviour and cognition.

Key references

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• Burrows EL, McOmish CE, Buret LS, Van den Buuse M, Hannan AJ. Environmental enrichment ameliorates behavioral impairments modeling schizophrenia in mice lacking metabotropic glutamate receptor 5. Neuropsychopharmacology 2015;40:1947-56.