Quantifying neuronal structural changes over time using dynamic morphometrics

Brain circuit development involves tremendous structural formation and rearrangement of dendrites, axons, and the synaptic connections between them. Direct studies of neuronal morphogenesis are now possible through recent developments in multiple technologies, including single-neuron labeling, time-lapse imaging in intact tissues, and 4D rendering software capable of tracking neural growth over periods spanning minutes to days. These methods allow detailed quantification of structural changes of neurons over time, called dynamic morphometrics, providing new insights into fundamental growth patterns, underlying molecular mechanisms, and the intertwined influences of external factors, including neural activity, and intrinsic genetic programs. Here, we review the methods of dynamic morphometrics sampling and analyses, focusing on their applications to studies of activity-driven dendritogenesis in vertebrate systems. Advances in single-cell labeling, rapid time-lapse imaging in awake developing vertebrate brains, and software for deep feature extraction from 4D data sets now allow rich quantification of neuronal growth.Tracking growth of individual neurons has revealed mechanisms of dendritogenesis not accessible from static images of different neurons at multiple maturational stages.Multiple independent rapid neurite growth behaviors, influenced by intrinsic genetic programs and extrinsic factors, culminate in dendritic arbors with both individual-neuron and neuron-type specific patterning.Dynamic morphometrics reveals that synapse formation and maturation stabilize growing dendrites.Dual in vivo imaging of neurite growth and neural activity reveals an intertwined relationship between synaptogenesis and dendritogenesis, allowing sensory experience to sculpt both dendritic arbor growth and receptive field tuning.