ABSTRACT
Beginning with the pioneering work of Golgi and Ramon y Cajal, neuroscientists have focused on developing methodologies to reveal structure and function within the nervous system (Ramon y Cajal 1995). Visualization of the
14.1 Imaging the Components of the Central Nervous System 355 14.1.1 Imaging Pathological Deposits in the Alzheimer Brain 356 14.1.2 Fluorescent Proteins 358 14.1.3 Cell-Type-Specific Promoters and Viruses 359
14.2 Imaging Cellular Structures 360 14.2.1 Imaging Mitochondrial Mobility 361
14.3 Imaging Neuronal Function 362 14.3.1 Calcium Imaging 362 14.3.2 Chloride Imaging 364 14.3.3 Voltage-Sensitive Dye Imaging 364 14.3.4 Measuring Immediate Early Gene Activation 365
14.4 Other Types of Imaging 366 14.4.1 Imaging Oxidative Stress 366 14.4.2 Imaging Vascular Function 366 14.4.3 Imaging Caspase Activity 367
14.5 Conclusion 368 References 368
nervous system has allowed insight into its development, maturation, and disease. Until recently, however, structural studies were largely limited to ex vivo preparations. The advent of imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), diffuse optical tomography (DOT), photoacoustic microscopy, bioluminescence tomography, and multiphoton microscopy has enabled in vivo imaging to flourish (Garcia-Alloza and Bacskai 2004; Luker and Luker 2008; Gibson and Dehghani 2009; Yao and Wang 2011). Optical techniques in particular have developed at a rapid pace, and a variety of imaging probes suitable for use in reduced preparations as well as in intact organisms have been generated. Here, we review fluorescent probes that have been used for in vivo imaging in the central nervous system (CNS) with high-resolution optical microscopy techniques. We have been implementing multiphoton microscopy combined with cranial window approaches to image structure and function in the brain. Multiphoton microscopy allows high-resolution imaging with a spectrum of fluorescent probes in living brain at depths of several hundred microns. Because the work in our laboratory is focused on Alzheimer’s disease, we have applied many of these tools to transgenic mouse models of the disease, and begin with an introduction to imaging the pathological deposits themselves. Despite our focus on disease, the use of optical imaging probes for in vivo imaging has broad applicability to healthy brain and other neurological disorders.
