News
Rhiannon Meredith awarded with VIDI grant
The project is focussed on developmental mechanisms in mouse models of mental retardation.
Mental retardation affects 2-3% of the worldwide population (WHO1997). A unifying pathological feature across many forms of mental retardation is abnormal shape of synaptic spines on neurons in the brain. Treatments are shifting from targeting comorbid symptoms such as epilepsy to focus on cognition: In Fragile X syndrome mental retardation, glutamate receptor antagonist drugs are in clinical trials for their potential neurocognitive effects. Abnormalities in spine pathology, however, are found in early postnatal development before the onset of cognitive symptoms.
In the VIDI project Rhiannon Meredith aims to resolve the development of glutamate receptor function and abnormal spine formation of individual synapses and synaptic networks to understand the mechanisms underlying early stages of retardation. In addition, she will target glutamatergic signalling during early postnatal development as potential therapeutic pathways for mental retardation treatments.
Experimental study of synaptic function in spine pathology disorders is made possible by transgenic mouse models of mental retardation, such as Fmr1-KO and MECP2 mice for Fragile X and Rett syndromes. Using the Fmr1-KO mouse, Rhiannon Meredith has previously shown that synapse pathology can be restored in young adulthood (see Meredith et al. 2007 Neuron paper). Using combined electrophysiology and multi-photon imaging, she will continue to study development of individual synapses and synaptic networks and target glutamatergic signalling in both newborn and adult mice following in vivo drug treatments. The results will enhance our understanding of glutamate receptors in spine pathologies during immature brain development, with a view to early-intervention treatment strategies in mental retardation.
The impact of this project is considerable. Indeed, development of cognitive function requires the formation and function of synaptic connections between neurons in the brain. Abnormal synaptic connections are a unifying feature of brain tissue from many different mental retardation syndromes and their corresponding transgenic mouse models. Current estimates from the World Health Organisation are that 2-3% of the world’s population, approximately 170 million people, has some form of mental retardation. This VIDI project focuses directly on using an early developmental approach to target synaptic spine pathologies underlying mental retardation and to measure the outcome of treatments during neonatal brain development, before cognitive and behavioural impairments of such syndromes are apparent.
