Autapses

Abstract

What is an autapse? An unusual kind of synapse: a synapse is a specialized connection between neurons or between a neuron and a muscle, used for transmitting electrical signals, and an autapse is a self-synapse — a connection between a neuron and itself. Why are autapses unusual? Normally we think of the nervous system as a collection of neurons daisy-chained together by synapses, allowing the flow of information from place to place. Autapses are odd because they seem incestuous. Why should a neuron wish to transmit information back to itself? Self-stimulation, in the brain, as elsewhere in biology, seems unproductive. So what are autapses good for? For many years, autapses in the brain had seemed like anatomical curiosities of unknown practical utility. Quite recently, however, experiments have begun to expose ways in which autapses might play subtle, but important, roles in brain function. One kind of experiment suggests that autaptic self-inhibition might act like a pendulum in a clock, maintaining the precision with which a neuron fires trains of action potentials and thereby paces other neuronal circuits. Other experiments have suggested that autapses may allow a unique kind of regional self-control. By targeting autapses to just one or two of its dendritic branches, a neuron may custom-control parts of itself. Are there different types of autapses? As is the case for brain synapses, autapses come in two main flavors: excitatory (glutamate-releasing) and inhibitory (GABA-releasing). Apart from being reflexive, these seem to operate just like their synaptic counterparts. Autapses should not be confused with spillover transmission, whereby neurotransmitter released at some conventional synapses can spill out of the synapse and activate the releasing neuron. Spillover transmission is not regarded as autaptic because it lacks a synaptic specialization and is often slower and weaker than true autaptic transmission. How common are autapses? Anatomically, autapses are not uncommon in the brain. They have been described in a variety of brain regions, including the neocortex, hippocampus, cerebellum, substantia nigra and striatum. In most of these cases autapses are sparse. An exception is a class of inhibitory neurons in the neocortex, the so-called fast-spiking cells, which make abundant autapses. It seems sensible that autapses are more common on inhibitory neurons, because they are inherently self-limiting. In contrast, autaptic self-stimulation by an excitatory neuron (‘positive feedback’) could lead to runaway excitation and epilepsy, which is clearly not in the best interests of the brain. However, there is one big exception to all of this: autapses in cell culture. What about autapses in culture? It has been known for over 15 years that neurons grown in dissociated cell cultures can form profligate numbers of autapses, especially if they are grown in confined spaces (for example on ‘microdots’ or ‘islands’ of permissive substrate). Neither excitatory nor inhibitory neurons in culture show any reluctance to form autapses: upwards of a thousand per cell can be observed, two orders of magnitude greater than in vivo! Presumably this promiscuity is aided by the two-dimensional layout of cultures, in which a neuron's axon is much more likely to encounter its own dendrites than is the case in a three-dimensional brain. Interesting, but so what? Autapses in culture make it possible to study synaptic transmission in a single cell. This is a huge advantage for synaptic neurophysiologists. Many beautiful and important experiments have been performed using autaptic cultures.