Electrophoretic migration due to postsynaptic potential gradients: Theory and application to autonomic ganglion neurons and to dendritic spines

Abstract

A postsynaptic mechanism for transforming electrical activity at a synapse into structural modifications near the synapse is proposed. The firing of a synapse produces a postsynaptic potential which is attenuated as it spreads electrotonically into other parts of the neuron. The potential difference so generated gives rise to an intraneuronal electric field, and permits the electrophoretic migration of charged metabolites, both along the inner surface of the membrane and in the cytoplasm. Estimates of the sizes of these fields suggest that they can play a significant role in locally organizing the distribution of the charged species, thus allowing differential biochemical activity at different synaptic locations. The mechanism is applied first to the innervation pattern found in ciliary ganglion neurons by Purves and Hume [(1981) J. Neurosci. 1, 441–452]. They showed that although ganglionic neurons are multiply innervated in early postnatal life, adult neurons are innervated such that the number of separate pre-ganglionic axons is approximately proportional to the number of major ganglionic dendrites. It is demonstrated how electrophoretic competition can result in individual dendrites establishing individual domains of innervation. The electrophoretic mechanism is next applied to dendritic spines. Theoretical calculations are presented which show that synaptic activity at a spine head can establish large electric fields along the spine, whereas synaptic activity at the base of the spine generates very small electric fields in the spine. The thinner the spine, the stronger the fields. If one assumes that these electric fields can lead to electrophoretic migration of charged metabolites necessary for either synaptic stabilization or enhancement, significant accumulation should occur within spines. Because the electric fields are small along the spine when electrical activity is generated elsewhere in the neuron, charged metabolites should not easily be drawn out of a spine. As a result, it is proposed that dendritic spines provide an anatomical means to reduce competition between neighboring afferent inputs. It is also shown how two other sets of experimental observations illustrate the electrophoretic effect. They are calcium action potentials in growth cone areas and membrane heterogeneity in myelinated axons.