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Network formation and reorganization

During development, neurons are able to form synaptic connections when their axonal and dendritic arbors come in close proximity to each other. Although many signaling mechanisms, such as chemical attraction and repulsion, are involved in steering neuronal arbors prior to synapse formation, the extent to which accidental appositions between axons and dendrites can account for synaptic connectivity remains unclear.

To explore what synaptic connectivity patterns can emerge from neuronal morphology alone, we generate in our simulation framework NETMORPH (Koene et al., 2009) cortical networks of morphologically realistic neurons among which synapses are formed when axonal and dendritic branches come within a threshold distance of each other.

Synapse formation is also modulated by electrical activity. In particular, the formation of axonal boutons and dendritic spines, the pre- and postsynaptic parts of synapses, is regulated by electrical activity—not only during development but also in the adult brain. For example, persistent alterations in afferent activity to the cortex, such as those caused by retinal lesions, trigger extensive spine dynamics, leading to a massive reorganization of cortical synaptic connectivity.

The principles governing these structural changes are, however, poorly understood. From the way electrical activity influences neurite outgrowth and spine and bouton formation, we hypothesize that neurons try to maintain their average level of electrical activity at a particular set-point (homeostatic regulation).

To examine whether homeostatic rules for spine and bouton formation (homeostatic structural plasticity) may guide the development and reorganization of cortical synaptic connectivity, we use our model of structural plasticity (MSP; Butz et al., 2008; Van Ooyen, 2011), in which each neuron creates new spines and boutons when its level of electrical activity is below a homeostatic set-point and deletes spines and boutons when activity is above the set-point or below a certain minimum level. Spine and bouton formation depend solely on the neuron's own activity level, and synapses are formed by merging spines and boutons independently of activity. Recently, MSP has been implemented in the neuronal network simulator NEST to study structural plasticity in large-scale neuronal networks (Diaz-Pier et al., 2016).

MSP, which simulates the dynamics of spine and bouton formation, was partly derived from a less detailed model of homeostatic structural plasticity that uses circular neuritic fields to emulate the activity-dependent growth of axons and dendrites. This latter model was used to study network assembly (e.g., Van Ooyen et al., 1995) and retinal mosaic formation (Eglen et al., 2000; see movies) and more recently also the development of self-organized criticality (Tetzlaff et al., 2010; Kossio et al., 2018). A new book chapter (Van Ooyen and Butz-Ostendorf, 2019) reviews model studies that show that activity-dependent neurite outgrowth can build critical networks.

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