The regulation of dendritic arbor development and plasticity by glutamatergic synaptic input: a review of the synaptotrophic hypothesis

Abstract

The synaptotropic hypothesis, which states that synaptic inputs control the elaboration of dendritic (and axonal) arbors was articulated by Vaughn in 1989. Today the role of synaptic inputs in controlling neuronal structural development remains an area of intense research activity. Several recent studies have applied modern molecular genetic, imaging and electrophysiological methods to this question and now provide strong evidence that maturation of excitatory synaptic inputs is required for the development of neuronal structure in the intact brain. Here we critically review data concerning the hypothesis with the expectation that understanding the circumstances when the data do and do not support the hypothesis will be most valuable. The synaptotrophic hypothesis contributes at both conceptual and mechanistic levels to our understanding of how relatively minor changes in levels or function of synaptic proteins may have profound effects on circuit development and plasticity.

Figure 1. Dendritic arbor growth and synapse maturation are concurrent

The diagram shows an immature neuron with a simple dendritic arbor and excitatory synapses which are predominated by NMDA-type glutamate receptors. As the neuron matures, the dendritic arbor becomes more complex and the synapses mature by adding AMPA-type glutamate receptors.

Figure 2. Expression of peptides corresponding to the C terminal of glutamate receptor subunits decreases the amplitude of spontaneous miniature synaptic currents (A) and alters the dendritic arbor development of optic tectal neurons (B)

Gray lines in A are data from neurons expressing GluR1 (top) and GluR2 C terminal peptides (bottom). Black lines are from GFP-expressing control neurons. Adapted from Haas et al. (2006).

Figure 3. Blocking glutamatergic synapse maturation prevents experience-dependent dendritic arbor growth

Control GFP-expressing neurons increase the relative rate of dendritic arbor growth as a result of 4 h of enhanced visual experience. Neurons expressing the AMPAR C terminal peptides do not respond to the visual stimulation with an increased growth rate.

Figure 4. The synaptotrophic hypothesis states that synaptic inputs drive the development of the dendritic arbor

Interfering with synapse maturation prevents normal dendritic arbor growth and would be predicted to affect circuit function.