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Final Report Summary - PVPITM (Gain controls in parallel visual pathways of the mouse)

Goals of the research project
The overall goal of this project was to understand how nerve cells - in the parts of the brain that receive inputs from the eye - respond to visual patterns. Particularly we wanted to know how the visual response of these nerve cells is regulated. How visual response is regulated is important, because the regulatory processes can prevent or accentuate both how we perceive and how we unconsciously respond to visual patterns. It is believed that disorders in these regulatory mechanisms may be important in several eye and brain disorders. Understanding these regulatory mechanisms may therefore open avenues to new therapies and diagnostic tools for visual and other brain disorders.

Work carried out
The research in this project involved measuring the activity of nerve cells in the brain areas that are the major targets of the eye's output, using the mouse as an experimental model. Measurements were made in anaesthetised animals, and in awake animals, while they viewed a computer screen that displayed visual patterns. We were able to measure the response of individual nerve cells and characterise the way in which they responded to these patterns. We used simple models of nerve cell function to explain these responses, and understand how these cells 'interpret' visual images. In addition to these measurements, we developed new behavioural tests that allow us to show how mice respond to visual stimuli, providing a potential link between nerve cell activity and behavioural responses. We also helped develop functional magnetic resonance imaging to measure the distribution of visually-evoked activity across the mouse brain, and allow comparison with similar measures in human brain.

Main results and conclusions
Our recordings show the presence and impact of regulatory mechanisms in the primary brain target of the mouse eye - the mid-brain superior colliculus - as well as the secondary visual pathway that passes through the thalamus to the cerebral cortex. The recordings have demonstrated that even in the mid-brain these regulatory mechanisms are often tuned for the spatial form of simple patterns and that this tuning is stronger during wakefulness than during anaesthesia. Additionally we find evidence for (temporal) mechanisms that reduce responses to repeated presentations of stimuli. These regulatory mechanisms therefore profoundly influence the signals that are carried by nerve cells in the visual system - they reduce responses to visual patterns that are expected, or that are the same as their surroundings. The regulatory mechanisms must influence how easy it is to see and respond to visual objects (that is, how salient they are). Unexpectedly, we find that nerve cells that show strong spatial regulatory mechanisms also show strong temporal regulatory mechanisms, and that the effect of these mechanisms can be dissociated. Our results therefore reveal mechanisms in evolutionary-conserved visual pathways that may be important in helping the brain detect and respond to salient objects in the environment, and suggest dedicated pathways through the brain that carry signals about salience. These results therefore provide fundamental knowledge about key determinants of visual sensitivity. We hope that in the longer term our results will help understanding of how to detect and treat abnormal function of the visual system.

Potential impact
In addition to the knowledge gained, the impact of this work to date includes the synthesis of a model of gain controls in visual (and wider) sensory processing, a new test of visual behaviour in animals, new fMRI methods for helping translate knowledge from animal models to humans, and potentially new avenues for understanding the impact of neurodegeneration on brain function. This career reintegration grant has also enabled integration of Dr Solomon's research programme into Europe, by helping him develop research networks in his host institution (UCL) and more broadly, providing him a research base with which to secure a permanent position, and facilitating successful grant applications to the Biotechnology and Biological Sciences Research Council, the Wellcome Trust, and Research to Prevent Blindness. This grant also supported the training of exceptional young European researchers including the PhD candidature of Ms Gioia De Franceschi (now continuing her scientific career as a postdoctoral researcher in Switzerland), postdoctoral researcher Dr Amalia Papanikoloau (who has developed her skill base by training in cellular recording methods) and Erasmus+ student Mr Risto Jamul (now a PhD student at Kings College in London).

Website: Information about the aims of the grant, the funding provided, and publications arising are published on-line on the laboratory website (http://solomonlab.info/#/menu/)

Reported by

UNIVERSITY COLLEGE LONDON
United Kingdom

Subjects

Life Sciences
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