Beginning at the end: repetitive firing properties in the final common pathway

Abstract

Since the early 20th century, it has been recognized that motoneurons must fire repetitive trains of action potentials to produce muscle contraction. In 1932, Sir John Eccles, together with Hebbel Hoff, found that action potential spike trains in motor axons were produced by "rhythmic centres", which were within the motoneurons themselves. Two decades later, Eccles attended a Cold Spring Harbor Symposium in NY, USA entitled "The Neuron". Two of the many notable presentations at this symposium were juxtaposed: one by Eccles from the University of Otago, Dunedin, NZL, and the other by J. Walter Woodbury and Harry Patton from the University of Washington, Seattle, USA. Both presentations included data obtained using sharp microelectrodes to study the intracellularly recorded potentials of cat motoneurons. In this review, I discuss some of the events leading up to and surrounding this jointly accomplished advance and proceed to discussion of subsequent studies over 5+ decades that have made use of intracellular recordings from motoneurons to study their repetitive firing behavior. This begins with early descriptions of primary and secondary range firing, and continues to the discovery of dendritic persistent inward currents and their relation to plateau potentials, synaptic amplification, and motoneuronal firing. Following a brief description of the possible mechanisms underlying spike frequency adaptation, I discuss the modulation of repetitive firing properties during various motor behaviors. It has become increasingly clear that the central nervous system has exquisite control of the repetitive firing of motoneurons. Eccles' work laid the foundation for the present-day study of these processes.

Fig. 1

A reproduction of Fig. 35 in Eccles and Hoff (1932). The original figure legend read: “Schematic representation of rhythmic discharge and the action of a single antidromic impulse” (p. 507). The associated text read: “The production of a rhythmic reflex discharge according to the conditions postulated is illustrated in Fig. 35, where intensities of c.e.s. are plotted as ordinates against time as absicssae. OF is the line of zero intensity of c.e.s. According to the fourth assumption the intensity of c.e.s., OA, at the point A just after a reflex discharge, equals half the threshold intensity OL. As a result of its uniform production and spontaneous subsidence, c.e.s. is represented as increasing in intensity during normal rhythm along the line AM to again attain threshold at M, where the next reflex discharge is set up. The intensity of c.e.s. falls from M to B, and then increases along the line BN, till at N another reflex discharge is set up, with a consequent fall of c.e.s. to C followed by an increase to P, and so on. By assumption an antidromic impulse acting at a point D, Fig. 35, inactivates an intensity. . . of c.e.s., as shown by the line DE, and c.e.s. then increases along the line ER to regain a threshold intensity at R, where a reflex discharge is set up” (pp. 507–509). The text also provided a mathematical description of these relations and a derivation of the relationship between T2 and T1. Reprinted with permission of the publisher.

Fig. 2

A reproduction of Figs. 1 and 2 in Brock et al. (1951a). These are the first known illustrations of an intracellular record from a vertebrate central neuron. The original figure legend read: “Figs. 1 and 2. Intracellular action potentials of motoneurons as described in the text. Potential and time scales common to both figures.” (p. 15). Their Fig. 1 illustrates orthodromically evoked APs evoked by stimulation of group I afferents, with the EPSP shown below. Their Fig. 2 illustrates an antidromically evoked AP, with the dotted line demonstrating a superimposed orthodromic spike. Reprinted with permission of the publisher.

Fig. 3

A reproduction of Figs. 2 and 8 in Kernell (1965b) demonstrating primary and secondary range firing in a cat motoneuron. The plot in his Fig. 2 is of steady-state firing frequency vs. injected current, and the numbers are the slopes of the primary and secondary range of firing in Hz/nA. His Fig. 8 is a schematic f–I graph demonstrating the primary and secondary ranges for first interval vs. steady-state firing. Reprinted with permission of the publisher.

Fig. 4

A reproduction of Fig. 2A in Hounsgaard et al. (1984) demonstrating sustained firing in a cat motoneuron. The discharge was produced by a short pulse of depolarizing current injection and terminated by a hyperpolarizing pulse. The authors demonstrated that the self-sustained discharge was due to an underlying plateau potential. Reprinted with permission of the publisher.