Imaging the Brain in Action: Real-Time Voltage- Sensitive Dye Imaging of Sensorimotor Cortex of Awake Behaving Mice

In: In Vivo Optical Imaging of Brain Function. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2009. Chapter 6.


Electrophysiological measurements have demonstrated that information can be processed on the time scale of milliseconds in the mammalian brain. Neuronal electrical changes are probably the fastest events occurring in the nervous system, and they are likely to orchestrate many of the subsequent slower events, such as changes in second-messenger concentration, structural alterations, and regulation of gene expression. Whereas electrophysiological recordings from individual electrodes have revealed many important aspects of brain function, it is also clear that complex neuronal processing of information does not derive from the activity of individual neurons, but rather results from the concerted actions of many neurons distributed across different brain areas. Indeed, considerable progress has been made toward increasing the number of electrodes in electrophysiological recordings in order to begin to understand the coordinated function of neuronal networks [1–2]. Despite these very important technical developments, it remains clear that the spatial organization of neuronal electrical activity will be difficult to study with electrophysiological approaches, even using arrays of more than 100 electrodes. Optical methods allow high-resolution imaging and therefore provide a useful tool to explore the spatial distribution of neuronal activity, especially in superficial brain structures such as the cerebral cortex. Indeed, quite remarkably, there are intrinsic changes in reflected light from the cortical surface, which can be easily measured and provide high spatial resolution maps of cortical organization [3–6]. However, these intrinsic changes in light absorption and scattering of brain tissue do not relate directly to neuronal electrical activity, but instead result primarily from hemodynamic changes, in a similar way to the BOLD fMRI signal. In order to make optical measurements that relate directly to electrical activity, it has so far proven necessary to apply dyes that change their absorption or emission spectra in a manner depending upon membrane potential. Such compounds are termed voltage-sensitive dyes.

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