, 2010), biophysically realistic computational modeling, and potential connectivity mapping. By reproducing branch topology and meandering, digital reconstructions faithfully capture both global properties and local features of neurons. Thus, digital reconstructions recapitulate the functional essence of neuronal morphology (Figure 3). Results obtained in cellular anatomy with the aid of digital reconstructions include comparative

morphological characterizations of neurons, quantification of changes during development and pathology, determination of the genetic underpinning of neuronal structure, and establishment of general principles underlying neural circuitry. Moreover, three-dimensional tracing is now routinely employed to implement detailed computational simulations of biophysical mechanisms underlying growth and electrophysiological activity. Early neuronal digital reconstructions were primarily used for quantitative morphological Ivacaftor in vitro description of axons and dendrites in a range of species (Halavi et al., 2012). Neuronal reconstructions have been employed in direct comparative studies across species VX-770 (Chmykhova et al., 2005), cell types (Bui et al., 2003; Andjelic et al., 2009), and hemispheres (Hayes and Lewis, 1996). Morphological investigations have also led to the discovery of new neuron types (e.g., Le Magueresse et al., 2011). Additionally, digital reconstructions can quantify morphological aberrations in pathological

conditions, experience-dependent morphological changes, and morphological changes during development. Finally, the ever-increasing use of transgenic mice has vastly expanded research on the genetic factors in axonal and dendritic morphology,

including protein regulation in the maturation and specification of neuron identity (Franco Sitaxentan et al., 2012; Sulkowski et al., 2011; Michaelsen et al., 2010). Statistical distributions of geometrical features extracted from digital reconstructions have aided the search for general principles underlying dendritic and axonal branching (Cuntz et al., 2008; Wen and Chklovskii, 2008; Snider et al., 2010; Teeter and Stevens, 2011) and computation (Seidl et al., 2010). Virtually embedding three-dimensional tracings in a template atlas of the brain enables analysis of system stereology, such as space occupancy (Oberlaender et al., 2012; Ropireddy et al., 2012). In recent years, whole-brain 3D atlases have been acquired along with internally registered neuronal reconstructions in several insect models, constituting important progress toward the generation of comprehensive connectivity maps in these species (Kvello et al., 2009; Wei et al., 2010; Rybak et al., 2010; Chiang et al., 2011). Even the morphological reconstructions of a handful of individual neurons can allow derivation of potential connectivity patterns by computational analysis of the spatial overlap between axons and dendrites (Stepanyants et al., 2002).