Professor Frank Sengpiel FLSW, DPhil Oxon

Professor Frank Sengpiel

FLSW, DPhil Oxon

Head of Neuroscience Division, Professor of Neuroscience

School of Biosciences

Email:
sengpielf@cardiff.ac.uk
Telephone:
+44(0) 29 2087 5698
Location:
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX

Research Overview

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.

Research over the past 20 years has identified a large number of molecules and pathways that are involved in developmental plasticity as well as in the regulation of the critical period during which the cortex is particularly susceptible to being shaped by sensory experience and indeed requires appropriate experience to develop normally. Glutamate receptors and their downstream signalling pathways play a key role in synaptic plasticity. Gene defects affecting some of the associated postsynaptic proteins have been shown to cause neurodevelopmental disorders (also known as synaptopathies) such as Fragile X. We study developmental plasticity in V1 in models of those disorders using functional brain imaging methods, namely optical imaging of intrinsic signals and two-photon laser scanning microscopy.

Public Engagement

I am the academic lead for public engagement of the Neuroscience & Mental Health Research Institute. Among other things, I have instigated the participation of Cardiff University in the annual Brain Awareness Week (BAW) and have talked on BBC Radio Wales about the brain in the run-up to this event. I have organised an annual public lecture in neuroscience since 2010. I also take part in the annual "Learn about Life" event aimed at primary school children. Finally, I have initiated participation in the international Brain Bee competition (aimed at senior secondary school pupils, GCSE to A level), for which the first Welsh championship was held in 2011.

The biggest event in 2013 and 2014 has been the Brain Games held at the National Museum during BAW. The Brain Games – originally funded by a Wellcome Trust Engaging Science award - is a competitive event aimed at 8-11 year olds, where children collected points for taking part in a number of brain-related activities that showed an aspect of the brain studied at Cardiff. Prior to the event, we ran assemblies in 6 local primary schools, and launched a 'brain art' competition the winner of which was chosen by the public at the Brain Games. We are now planning to repeat the Brain Games in March 2015, and to take our assembly to every primary school in the Cardiff area.

  • Diploma in Biology, Ruhr University, Bochum, Germany (1989)
  • DPhil in Physiology, University of Oxford (1994)
  • Junior Research Fellow, Magdalen College, Oxford (1993-1996)
  • Research Fellow, Max-Planck Institute of Neurobiology, Munich (1996-2000)

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 V1 in response to monocular deprivation (above) and recovery from it (below). We have recently shown that spending a week in total darkness speeds up this recovery (Fig. 1; Erchova et al. 2017, Phil Trans R Soc Lond B)

Fig. 1: Time course of OD index as a measure of recovery from MD, obtained by chronic imaging of mice with (+DE) and without a week of dark exposure (-DE2)

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 studied the role of the AMPA receptor subunit GluA1 (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).

A number of postsynaptic density proteins and downstream signalling molecules have been found to be associated with a range neurodevelopmental disorders sometimes called synaptopathies. We are studying mouse models of these conditions in order to better understand their neurodevelopmental effects and to find ways to alleviate them.

Finally, we are interested in both how visual information is fed forward from V1 to higher visual areas as well as non-visual areas, and how feedback from other cortical areas influences information processing in V1. In order to investigate these questions we study neuronal responses in mice performing behavioural tasks on which they have been trained (Fig. 2.)

Fig.2: A: Schematic of the visual discrimination task. The mouse was placed on a locked cylindrical treadmill while the right visual cortex was imaged using two-photon microscopy. Visual gratings appeared on the ipsilateral side to imaging in the focused task and both the ipsilateral and contralateral sides during the divided attention task. B: The behavioural programme consisted of a quiescent phase which was re-set if the animal licked the spout, a tone and then the onset of the visual stimulus 1 second after. The visual stimulus drifted for four seconds and the animal was only required to respond in the final half, referred to as the response window. C: Performance increased as training days increased, reaching high performance at day seven and consistently staying above this thereafter. D: Raster plots how that lick behaviour is different when animals are trained between the Go (top) and Nogo (bottom) conditions.

Active Grants

BBSRC Project Grant
Homeostatic plasticity in mouse visual cortex (PI)

BBSRC Project Grant

Stimulus processing and control by the retrosplenial cortex (CoI)

Wellcome Trust 4-year PhD programme

Integrative Neuroscience (CoI)

Collaborators

Adam Ranson, Cardiff University, School of Medicine

John Aggleton, Cardiff University, School of Psychology

Seralynne Vann, Cardiff University, School of Psychology

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

Research Team Members

Asta Vasalauskaite, Eluned Broom, Michal Milczarek, Fangli Chen, Stephanie Bagstaff, Mariangela Lemoli