United Kingdom Research and Innovation, Medical Research Council and King's College London
Uwe Drescher, Professor of Molecular Neurobiology – Centre for Neurodevelopmental Disorders
Photograph of Uwe Drescher

Uwe Drescher

Professor of Molecular Neurobiology

Research overview

One approach to better understand the aetiology of autism spectrum disorder (ASD) is to take genes with changes identified in people with autism, generate mice mirroring these genetic differences, and analyse functionally and structurally the neural circuits that result. We are working on an understanding of structural changes in neural connectivity in mice mutant for the high confidence ASD gene Cntnap2, a member of the neurexin family. Cntnap2 is involved in the stabilisation of synapses, while other members of the neurexin family typically have synaptogenic activities.

We focus our analyses on parts of the medial prefrontal cortex and somatosensory cortex - regions believed to function as hubs to integrate neural circuits controlling social behaviours. We study the development of circuits in these areas from the postnatal period to adult mice which enables us to detect transient defects in neural circuit development. To facilitate our analysis, we have generated Cntnap2 mutant mice in which a small fraction of pyramidal neurons from layers 2/3 and 5 are specifically labelled, allowing high-resolution analyses of excitatory neural circuits, projection patterns, and synaptic connectivities.

We have found that transient disturbances in the density and form of dendritic spines of layer 2/3 and layer 5 pyramidal neurons affects the balance between excitation and inhibition in these areas. We are now focussing on a disruption of long-range projection patterns of these pyramidal neurons. To understand the defects on a molecular level, we are also investigating the hypothesis that spine pruning is disrupted due to a disturbance of microglia function and/or neuronal autophagy in Cntnap2 mutant mice and if changes in the inhibitory circuitry occur. 

Selected Publications

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