Prof Frank Sengpiel
We study the mechanisms of normal development of the primary visual cortex (V1) and the physiological and molecular basis of common developmental disorders of vision such as amblyopia (lazy eye). Specifically, we examine the effects of various rearing regimens on the two principal response characteristics of neurons in V1, binocularity and orientation selectivity.
The primary visual cortex (V1) is one of the most extensively studied areas of the mammalian brain. For a long time, the issue of "nature versus nurture" has been of particular interest: to what extent is the way we see the world determined by intrinsic factors such as our genes, and how far are our visual abilities shaped by the environment, that is by our own visual experience during the so-called critical period?
We visualize cortical activity by means of "optical imaging of intrinsic signals", and we image activity at the level of individual neurons by two-photon laser scanning microscopy. We can thus assess ocular dominance (OD) plasticity in response to monocular deprivation (above) and postnatal refinement of retinotopic maps in V1 (below).
We are investigating the molecular basis of normal as well as abnormal visual cortical development. Glutamate receptors and their downstream signalling pathways are known to play a key role in synaptic plasticity. We have recently studied the role of the AMPA receptor subunit GluR1 (the loss of which results in LTP/LTD deficits) in the developmental plasticity of mouse V1. We also discovered a significant strain difference in OD plasticity between two common used strains of C57BL/6 mice (Ranson, Cheetham, Fox & Sengpiel, PNAS 2012, in press).
A number of postsynaptic density proteins and downstream signalling molecules have been found to be associated with a range neurodevelopmental disorders sometimes called synaptopathies. Perhaps the best-known of these is Fragile X which is caused by a loss-of-function mutation in the FMR1 gene which codes for the protein FMRP and constitutes the most common single-gene cause of autism. Another is non-syndromic mental retardation caused by mutation of the DLG3 gene which codes for SAP-102, a membrane-associated guanylate kinase that forms part of the NMDA receptor complex. We are studying mouse models of these conditions in order to better understand their neurodevelopmental effects and to find ways to alleviate them.
BBSRC Project Grant
Cellular mechanisms of developmental plasticity in mouse primary visual cortex
EC FP7 Research Grant
EuroV1sion: Imaging function and dysfunction of neuronal circuits in visual cortex
Kevin Fox, Cardiff University, School of Biosciences
James Morgan, Cardiff University, School of Optometry & Vision Sciences
Peter Kind, University of Edinburgh, Scotland
Donald Mitchell, Dalhousie University, Halifax, Canada
James Fawcett, University of Cambridge
Research Team Members