Title: Neurophysiology of behaviour
Funder: The Francis Crick Institute

Abstract: Understanding how complex behaviour emerges from the properties of molecules, cells and ensembles of cells is one of the key challenges in neuroscience. The first part of the Neurophysiology of Behaviour laboratory tackles this question employing the olfactory system of mice as a model system. To understand how smells are processed we modify specific selected brain areas - in particular the olfactory bulb - using transgenic mice, pharmacological tools or targeted virus injections. We then probe how these specific modifications alter the neural networks and the resulting cellular function and physiology in vivo during behavioural tasks using whole-cell patch-clamp recordings, 2-photon microscopy and unit recordings. Ultimately, we perform quantitative behavioural tasks in such modified mice. We combine volume electron microscopic analysis of the olfactory bulb (using serial block-face scanning electron microscopy of columes of up to 0.2 mm^3) with functional analysis in vivo in order to delineate the underlying anatomical substrate and provide a mechanistical basis for our understanding of physiological responses. Combining these genetic, physiological, anatomical and behavioural techniques with computational modelling approaches we aim to elucidate the cellular basis of olfactory behaviour and ultimately more general complex behaviours. A second part of the Neurophysiology of Behaviour Laboratory aims to develop tools to enable large-scale electrophysiological recordings to benefit both basic neuroscience research and neuroprosthetics. Current electrical recording technologies in neuroscience are held back by the difficulty of fabrication. An electrode is connected to a plug, which is connected to a pre-amplifier, which is connected to digitization equipment. These components are fabricated separately and then assembled by hand, limiting their minimum size. For that reason, the number of simultaneously recorded neurons have in the past not scaled with Moore’s law (doubling every 2 years), as it arguably should, but far slower (doubling every 7 years). While there are some systems under development aimed at locally multiplexing of neural signals, they are still generally based on specialized hardware unlikely to scale efficiently. To overcome this, we develop technology around easily tailored bundles of glass-sheathed metal microwires. These mechanically connect to the surface of a camera chip readout integrated circuit (ROIC). By harnessing the already highly-developed microscale electronic readouts and amplifiers for each pixel in the ROIC, we aim to record from up to 106 individual wire elements. These pixels will be mated to glass-sheathed gold microwires 5-30 µm in diameter which can be inserted into the brain and individually addressed. This part of the lab strongly benefits from collaborations with material scientists, engineers, and computational neuroscientists, enabling us to develop all necessary components that will make it possible to obtain unprecedented amounts of data about neural activities in vivo.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL