Backpropagation of action potentials generated at ectopic axonal loci: hypothesis that axon terminals integrate local environmental signals.

This review deals with the fascinating complexity of presynaptic axon terminals that are characterized by a high degree of functional distinctiveness. In vertebrate and invertebrate neurons, all-or-none APs can take off not only from the axon hillock, but also from ectopic axonal loci including terminals. Invertebrate neurons display EAPs, for instance alternating with somatic APs, during survival functions. In vertebrate, EAPs have been recorded in the peripheral and central nervous systems in time relationship with physiological or pathological neuronal activities. In motor or sensory axon, EAP generation may be the cause of motor dysfunctioning or sensory perceptions and pain respectively. Locomotion is associated with rhythmic depolarizations of the presynaptic axonal membrane of primary afferents, which are ridden by robust EAP bursts. In central axons lying within an epileptic tissue EAP discharges, coinciding with paroxysmal ECoG waves, get longer as somatic discharges get shorter during seizure progression. Once invaded by an orthodromic burst, an ectopic axonal locus can display an EAP after discharge. Such loci can also fire during hyperpolarization or the postinhibitory excitatory period of the parent somata, but not during their tonic excitation. Neurons are thus endowed with electrophysiological intrinsic properties making possible the alternate discharges of somatic APs and EAPs. In invertebrate and vertebrate neurons, ectopic axonal loci fire while the parent somata stop firing, further suggesting that axon terminal networks are unique and individual functional entities. The functional importance of EAPs in the nervous systems is, however, not yet well understood. Ectopically generated axonal APs propagate backwards and forwards along the axon, thus acting as a retrograde and anterograde signal. In invertebrate neurons, somatically and ectopically generated APs cannot have the same effect on the postsynaptic membrane. As suggested by studies related to the dorsal root reflex, EAPs may not only be implied in the presynaptic modulation of transmitter release but also contribute significantly during their backpropagation to a powerful control (collision process) of incoming volleys. From experimental data related to epileptiform activities it is proposed that EAPs, once orthodromically conducted, might potentiate synapses, initiate, spread or maintain epileptic cellular processes. For instance, paroxysmal discharges of EAPs would exert, like a booster-driver, a powerful synchronizing synaptic drive upon a large number of excitatory and inhibitory postsynaptic neurons. We have proposed that, once backpropagated, EAPs are likewise capable of initiating (and anticipating) threshold and low-threshold somatodendritic depolarizations. Interestingly, an antidromic EAP can modulate the excitability of the parent soma.(ABSTRACT TRUNCATED AT 400 WORDS)