Activity-Dependent Neurite Outgrowth: Implications for Network Development
Arjen van Ooyen
PhD thesis, University of Amsterdam, The Netherlands, 1995
197 pages
Empirical studies have shown that neuronal electrical activity influences
neurite outgrowth. High activity levels cause neurites to retract, whereas low levels allow further
outgrowth. The aim of this thesis is to explore, by means of computational models, the implications of
activity-dependent neurite outgrowth for neuronal morphology and network development.
To model the spatial extent of neurites, we provide each neuron with a circular neuritic field, the size of which depends on the neuron's own level of electrical activity. When activity is lower than a homeostatic set-point ε, the neuritic field expands, and when activity is higher than ε, the field retracts. Neurons connect synaptically when their neuritic fields overlap, with a connection strength proportional to the area of overlap. By adjusting the size of its neuritic field, each neuron effectively attempts to reach activity level ε, at which point neuritic field size and synaptic connectivity no longer change.
In Chapter 2, we study actvity-dependent outgrowth in purely excitatory networks, and show that one of the implications of actvity-dependent outgrowth is a transient overshoot of synaptic connectivity during development. Overshoot of connectivity is a characteristic feature of nervous system development, in vivo as well as in vitro.
In Chapter 3, we consider a purely excitatory network in which the value of ε varies among neurons. This variability gives rise to complex oscillations in both electrical activity and synaptic connectivity, the time scale of which is determined by the slow time scale of neurite outgrowth. Slow fluctuations in firing rate have indeed been observed in cerebral cortex cells, both in vivo and in vitro.
In Chapter 4, we show that even without such slow intrinsic processes, long periods of high network activity can alternate with long periods of low activity, as a result of spontanously firing cells interfering with activity patterns.
In Chapter 5, we examine activity-dependent outgrowth in networks that contain both excitatory and inhibitory cells (mixed networks). Although there are no intrinsic differences between the growth properties of both cell types, their neuritic fields nevertheless differentiate, with the neuritic fields of inhibitory cells becoming smaller than those of excitatory cells. In the cerebral cortex, the dendritic and axonal fields of inhibitory neurons are indeed smaller, on the whole, than those of excitatory cells.
Both purely excitatory and mixed networks are capable of self repair. After cell loss (stroke, neurodegeneration), the electrical activity of the remaining cells falls below ε, triggering neuritic field outgrowth and formation of connections until activity is restored.
In Chapter 6, we show that in contrast to purely excitatory networks, mixed networks have multiple equilibrium states. The network's initial conditions determine which equilibrium state is reached. Perhaps counter-intuitively, too much inhibition during early development prevents the normal pruning of connections and results in a network with high connectivity and epileptic-like electrical activity. Another implication of multiple equilibrium states is the presence of critical periods for pruning.
In Chapter 7, we study a growth function in which neurite retraction also occurs below a minimal level of electrical activity. This leads to a wider range of behaviours during network development, with the possibility of transient growth followed by total loss of connectivity in parts of the network.
Taken together, our results suggest that activity-dependent neurite outgrowth (a form of homeostatic structural plasticity) has considerable potential to control neuronal morphology and network connectivity.
Full text of whole thesis (PDF)
Book contents:
Cover material
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Glossary
[Full text: PDF]References
[Full text: PDF]Samenvatting
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[Full text: PDF]Dankwoord
[Full text: PDF]Curriculum Vitae
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