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shown to be an experimentally amenable model system even for the study of such
quintessential human physiological traits as alcoholism, drug abuse, and sleep [ 63 ].
Rodents, being mammals, have a brain structure that is similar but much smaller
than the human brain, and that therefore can be used to study cortical networks.
The mouse brain is an attractive model system to study, for example, the visual
system, due to the abundant availability of genetic tools allowing monitoring and
manipulating certain cell types or circuits [ 38 ]. The whisker-barrel pathway of the
rat is a relatively small and segregated circuit that is amenable to studying sensory
information processing at the molecular/synaptic, cell, and circuit/region levels.
21.3 Imaging Modalities Employed in Connectomics
We nowprovide an overviewof imagingmodalities that are used in obtaining connec-
tivity information. They differ in the spatial and temporal resolution at which connec-
tivity is captured. At the macroscale there is a wide range of structural and functional
imaging modalities, with applications in medical settings and anatomical research.
Functional imaging modalities include electroencephalography (EEG), magnetoen-
cephalography (MEG), functional magnetic resonance imaging (fMRI), and positron
emission tomography (PET). Modalities such as single-photon emission computed
tomography (SPECT) and magnetic resonance imaging (MRI) provide structural
information on the macroscale. Section 21.4 gives a detailed introduction to the rel-
evant modalities in the context of connectomics. At the mesoscale , light microscopy
(LM) techniques provide sufficient resolution to image single neurons. Most light
microscopy techniques focus on structural imaging. Techniques such as wide-field
fluorescence microscopy allow for the imaging of living cells, and computational
optical sectioning microscopy techniques [ 17 ] enable non-destructive acquisition
of 3D data sets. Section 21.5 provides further details about light microscopy tech-
niques. At the microscale , the sufficient resolution is offered by electron microscopy
techniques (EM) such as Transmission Electron Microscopy (TEM) and Scanning
Electron Microscopy (SEM). These methods require technically complex speci-
men preparation and are not applicable to live cell imaging. Imaging of 3D vol-
umes requires ultra-thin sectioning of the brain tissue followed by computational
realignment of the acquired images into one image volume [ 46 ]. More information
about electron microscopy in the connectomics setting can be found in Sect. 21.6 .
Figure 21.1 provides an overview of the different imaging modalities and their spatial
and temporal resolution.
21.4 Macroscale Connectivity
First, we discuss the main acquisition techniques for revealing macroscopic func-
tional and structural connectivity. We start with MEG and EEG, as these were used
for functional connectivity before fMRI, then diffusion-weighted MRI for structural
 
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