The molecular determinants of synaptic plasticity
Synaptic plasticity entails the change in function and morphology of the sites of excitatory neurotransmission known as dendritic spines. Accumulating evidence indicates that the structure and function of these dendritic spines needs to be coordinated for proper cognitive function, learning and memory as well as information storage. However, the molecular mechanisms that link these processes are incompletely understood. Aberrant alterations of dendritic spine morphology and synaptic plasticity contribute to the pathogenesis of neuropsychiatric diseases such as autism spectrum disorders and schizophrenia. The scope of the EU-funded MORPHINGSYNAPSES (The coordination of dendritic spine morphogenesis and function during synaptic plasticity and pathology) project was to study dendritic spine morphology and assess genetic risk factors in neuropsychiatric diseases. For this purpose, researchers used cutting edge imaging techniques and focused on two proteins: ankyrin-G – a key bipolar/schizophrenia risk gene and cadherin-10 – a risk factor for autism. By structured-illumination microscopy (SIM) and contrary to previous belief, researchers were able to define synaptic nanodomains of ankyrin-G. These alongside other proteins, localised to the dendritic spine. Results showed that ankyrin-G had an important function in maintaining dendritic spine morphology and synaptic plasticity. In parallel, scientists characterised the cellular function of cadherin-10, and found it to be located at both excitatory and inhibitory synapses. Taken together, MORPHINGSYNAPSES activities led to the identification of novel players in synaptic morphology and plasticity. Considering the implication of these proteins in neuropsychiatric disorders, these findings could help understand the molecular aetiology of these diseases and also serve as therapeutic targets.
Keywords
Synaptic plasticity, dendritic spine, cognitive function, ankyrin-G, cadherin-10, neuropsychiatric disorders
