Steps in the production of motoneuron spikes

1. Spikes evoked in spinal motoneurons by antidromic stimulation normally present an inflection in their rising phase. A similar inflection is present in spikes evoked by direct stimulation with short pulses. 2. In either case the inflection becomes less prominent if the motoneuron membrane is depolarized and more prominent when it is hyperpolarized. Both antidromic and direct spikes may fall from the level of the inflection thus evoking a "small spike" only if sufficient hyperpolarization is applied. Similar events occur when antidromic or direct spikes are evoked in the aftermath of a preceding spike. 3. Spikes evoked by direct stimuli applied shortly after firing of a "small spike" may also become partially blocked at a critical stimulus interval. At shorter intervals, however, spike size again increases and no inflection can be detected in the rising phase. 4. When a weak direct stimulus evokes a small spike only, a stronger stimulus may evoke a full spike. Curves of the strength of the stimuli required for eliciting small or full spikes have been constructed in a number of conditions. 5. To explain the results it is assumed that threshold of the major portions of the soma membrane is higher than the threshold of the axon, the transition occurring over a finite area near the axon hillock. Following antidromic or direct stimulation, soma excitation is then initiated in the region of the axon hillock. Spread of activity towards the soma occurs at first slowly and with low safety factor. At this stage block may be easily evoked. Safety factor for propagation increases rapidly as the growing impulse involves larger and larger areas of the soma membrane so that, once the critical areas are excited, activation of the remaining portions of the soma membrane will suddenly occur.     

Identification of Active Membrane Areas in the Giant Neuron of Aplysia

Intracellular and extracellular potentials were simultaneously recorded from the soma and different parts of the axon of the giant cell of Aplysia. Evidence was obtained that for all modes of stimulation the spike originates in the axon at some distance from the cell body. The conduction of the spike is blocked at a distance of 200 to 300 µ from the soma for the antidromic spike, closer to the soma for an orthodromic spike. This event is recorded in the soma as a small or A spike. After some delay, a spike is initiated in the resting part of the axon and in the axon hillock; the soma is invaded only afterwards. The response of these three parts of the neuron is recorded in the soma as the big or S spike.     

Site of Origin and Propagation of Spike in the Giant Neuron of Aplysia

The form and time sequence of spikes generated by orthodromic, antidromic, and direct stimulation and during spontaneous activity have been studied with intracellular electrodes simultaneously introduced in the soma and in different parts of the axon of the giant nerve cell of Aplysia. Evidence was obtained that under normal conditions of excitability, the spike originates at some distance from the soma in an axonal region with a higher excitability surpassing that of the surrounding membranes. Between the trigger zone and the soma is situated a region of transitional excitability where the conduction of the spike towards the soma may be blocked at a functionally determined and variable locus. The cell body is electrically excitable, but has the highest threshold of all parts of the neuron. The inactivation or even the removal of the cell body does not suppress synaptic transmission.     

Modes of Initiation and Propagation of Spikes in the Branching Axons of Molluscan Central Neurons

A study has been made of Aplysia nerve cells, mainly in the pleural ganglia, in which the main axon divides into at least two branches in the neighbourhood of the soma. Conduction between these branches was investigated by intracellular recordings from the soma following antidromic stimulation via the nerves containing the axonal branches. It has been shown that transmission between separate branches need not involve discharge of the soma but only of the axonal region between the soma and the origin of the branches. In some cells, the spike may fail to invade the other axonal branch, whereas transmission in the opposite direction is readily achieved. Often spikes in none of the branches are transmitted to the others, unless facilitated. Indications about the geometry of the neuron in the vicinity of the soma may be obtained from the study of the relative size of the A spikes originated in different branches. These observations, together with the presence of different sizes of A spikes, produced by orthodromic stimulation, provide evidence that spikes initiated at separate axonal "trigger zones" of Aplysia neurons may be conducted selectively to the effectors or other neurons innervated by the particular branch.     

Impulse Origin and Propagation in a Bipolar Sensory Neuron

Intracellular recording techniques were used to study electrical activity in bipolar sensory cells associated with crayfish tactile receptors. Several lines of evidence indicate that spikes evoked by natural stimulation of the receptor originate at a dendritic locus. Although overshooting spikes are recorded in the soma in response to both natural and antidromic stimulation receptor potentials are observed only rarely, and, when present, their amplitude is less than 5 mv. Impulses propagating centrifugally into the soma following antidromic stimulation always exhibit an inflection in the rising phase of the spike; however, orthodromic spikes are usually uninflected. Occasionally, orthodromic responses (in the soma) exhibit rather unusual wave forms. Such spikes evoked by natural stimuli are indistinguishable from those elicited electrically in the dendrite, but they do not resemble antidromic impulses. Because the axonal and dendritic boundaries of the soma have a low safety factor for spike transmission, at high frequencies invasion of the soma by dendritic spikes is impeded and often blocked. The soma region can thus act as a low-pass filter. The significance of this self-limiting mechanism for the behavior of the animal is not known; it is suggested, however, that this impediment is a potentially critical one, and may, in other situations, have encouraged the evolution of alternative arrangements.     

Corticofugal postsynaptic influences on red nucleus neurons

The responses of red nucleus neurons to stimulation of the sensorimotor cortex was studied on nembutal-anesthetized cats. Most of the rubrospinal neurons were identified according to their antidromic activation. Stimulation of the sensorimotor cortex was shown to evoke in the red nucleus neurons monosynaptic excitatory potentials with a latency of 1.85 msec, polysynaptic excitatory potentials (EPSP), and inhibitory postsynaptic potentials (IPSP) with a latency of 9–24 msec. The EPSP often produced spikes. The probability of generation of spreading excitation is greater with motor cortex stimulation. The monosynaptic EPSP are assumed to arise under the influence of the impulses arriving over the corticorubral neurons as a result of excitation of axodendritic synapses. The radial type of branching of red nucleus neurons facilitates the transition from electrotonically spreading local depolarization to an action potential triggered by the initial axonal segment. Polysynaptic EPSP and IPSP seem to be a result of activation of fast pyramidal neurons whose axon collaterals are connected via interneurons with the soma of the red nucleus neurons.L. A. Orbeli Institute of Physiology of the Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 43–51, January–February, 1971.     

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.     

Electrophysiological features of facial motoneurons in cats

Antidromic activation of facial motoneurons in cats during stimulation of different branches of the facial nerve was studied by intracellular recording. Time and amplitude characteristics of individual components of the antidromic action potentials were analyzed and fast and slow after-potentials distinguished. Correlation was found between the duration of the descending phase of the SD spike, duration of its after-hyperpolarization, and the spike conduction time along the axon. Data were obtained to show absence of a recurrent collateral pathway in motoneurons of the facial nucleus. The functional significance of the after-potentials is discussed.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 10, No. 3, pp. 261–270, May–June, 1978.     

A re-excitation mechanism for strychnine-induced doublets in molluscan neurons

The effects of strychnine on Aplysia R2 neurons were evaluated using simultaneous intracellular recordings of the soma and axon potentials. 1 mM strychnine produced a slight enlargement of the somatic spike and a large increase of the axon spike duration. Following direct stimulation, the soma displayed depolarizing afterpotentials ( DAPs ) which might trigger extra-spikes, both produced electronically by long-lasting axon spikes. Cobalt suppressed both the axon spike lengthening and the somatic extra-spikes or DAPs , and induced large depolarizing shifts in the soma. The region of largest spike lengthening (proximal axon) had a large density of Ca channels. The different effects of strychnine on the soma and on the axon were assumed to result from a selective blockage of the V-dependent K channels which would predominate in the axon whereas Ca-activated K channels would predominate in the soma.     

Electrophysiological investigation of the cat ciliary ganglion

Electrical responses of some nerves of the ciliary ganglion to stimulation of its other nerves were recorded, and intracellular recordings were also made from neurons of the ganglion (in situ). The overwhelming majority of preganglionic fibers terminate synaptically on neurons of the ganglion. Postganglionic fibers leave in the lateral and medial ciliary nerves, in which the velocity of conduction of excitation ranges from 1.9 to 9.0 m/sec. A few preganglionic fibers pass through the ciliary ganglion into the lateral ciliary nerve, giving off collaterals to neurons of the ganglion, so that stimulation of the lateral ciliary nerve evokes a response in the medial ciliary nerve (preganglionic axon reflex). The resting potential of neurons of the ciliary ganglion is 57±2.8 mV, and their action potential 68±3.6 mV. Single orthodromic stimulation usually evokes a single action potential in a neuron. The amplitude of the EPSP is increased during hyperpolarization of the postsynaptic membrane, confirming the chemical nature of synaptic transmission in the ganglion. The antidromic response consists of an IS-component and spike. The spike is followed by after-hyperpolarization, with a mean amplitude equal to 31% of the spike amplitude, and the time taken for it to fall to one–third of its initial amplitude is 75–135 msec.A. A. Bogomolets' Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 1, pp. 101–108, July–August, 1969.     

Antidromic indentification of hypothalamic neurosecretory cells in rats

Characteristics of antidromic action potentials of neurons of the paraventricular and supraoptic nuclei of the rat hypothalamus were studied during stimulation of the hypothalamo-hypophyseal tract by stimuli of varied amplitude and frequency. Step-like changes were found in spike latency in response to an increase in strength (up to 1.5–2.5 thresholds) or frequency (over 100 Hz) of stimulation, as well as cases with variation of the degree of division of the peak into A and B components. Injection of leu-enkephalin analog into the third ventricle or intravenous injection of NaCl solution (1 M) caused reversible changes in the level of excitability of antidromically activated neurons: leu-enkephalin mainly increased the latent period and threshold of action potential generation and reduced the reproducible frequency of stimulation to 10 Hz, whereas NaCl had the opposite effect. The results indicate that when the adopted criteria of antidromic identification of neurosecretory cells are used the level of their excitability must be taken into account.A. A. Ukhtomskii Physiological Research Institute, A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 14, No. 6, pp. 585–591, November–December, 1982.     

Electrical Properties of the Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria

In the Squilla heart ganglion, the pacemaker is located in the rostral group of cells. After spontaneous firing ceased, the electrophysiological properties of these cells were examined with intracellular electrodes. Cells respond to electrical stimuli with all-or-none action potentials. Direct stimulation by strong currents decreases the size of action potentials. Comparison with action potentials caused by axonal stimulation and analysis of time relations indicate that with stronger currents the soma membrane is directly stimulated whereas with weaker currents the impulse first arises in the axon and then invades the soma. Spikes evoked in a neuron spread into all other neurons. Adjacent cells are interconnected by electrotonic connections. Histologically axons are tied with the side-junction. B spikes of adjacent cells are blocked simultaneously by hyperpolarization or by repetitive stimulation. Experiments show that under such circumstances the B spike is not directly elicited from the A spike but is evoked by invasion of an impulse or electrotonic potential from adjacent cells. On rostral stimulation a small prepotential precedes the main spike. It is interpreted as an action potential from dendrites.     

Connections of neurons of the cat somatosensory cortex with the thalamic relay nuclei

Of 103 neurons in the rostral part of the posterior sigmoid gyrus of the cat cortex 30 responded to stimulation of the ventro-posterolateral and ventrolateral nuclei of the thalamus (VPL and VL), 42 responded to stimulation of VL only, and 31 to stimulation of VPL only. It was shown by intracellular recording that stimulation of VPL induces a spike response with or without subsequent IPSPs in some neurons and an initial IPSP in others. The spike frequency of single neurons reached 60/sec, but the IPSP frequency never exceeded 10–20/sec. Stimulation of VL was accompanied by: a) antidromic spike responses; b) short-latency monosynaptic EPSPs and spikes capable of following a stimulation frequency of 100/sec; c) long-latency polysynaptic EPSPs and spikes appearing in response to stimulation at 4–8/sec; d) short-latency IPSPs; e) long-latency IPSPs increasing in intensity on repetition of infrequent stimuli. It is concluded that the afferent inputs from the relay nuclei to neurons of the somatosensory cortex are heterogeneous. An important role is postulated for recurrent inhibition in the genesis of the long-latency IPSPs arising in response to stimulation of VL, and for direct afferent inhibition during IPSPs evoked by stimulation of VPL. It is shown that the rostral part of the posterior sigmoid gyrus performs the role of somatic projection and motor cortex simultaneously.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 4, No. 3, pp. 245–255, May–June, 1972.     

Projections from the ventral subiculum to supraoptical hypothalamic region neurons not responding to stimulation of the hypophyseal pedunculus

Effects of subiculum stimulation on spike activity of neurons localized in the supraoptical nucleus (SON) and perinuclear region were studied in experiments on rats; special attention was paid to neurons that did not respond to stimulation of the hypophyseal pedunculus. With rare exception, the SON cells did not respond to subiculum stimulation; 47% of neurons in the perinuclear region were activated after subiculum stimulation, whereas in 15% the frequency of spike activity decreased. Some neurons were found in the perinuclear region that responded to subiculum stimulation by antidromic spike generation.Organization of the studied afferent input to neurons of the supraoptical region and probability of interconnections between investigated structures are discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 4, pp. 253–257, July–August, 1993.     

Physiological characteristics and reflex activation of DUM (octopaminergic) neurons of locust metathoracic ganglion

Intracellular recordings were made from single or pairs of somata of the dorsal unpaired median (DUM) neurons of the metathoracic ganglion of the locust Schistocerca gregaria and the grasshopper Romalea microptera, during reflex actions, direct electric excitation and orthodromic and antidromic neural stimulation. Some, possibly all, of these neurons are unique, identifiable individuals in regard to their targets, which are specific peripheral muscles. Their physiological properties and the ways they are activated synaptically are, however, similar. Large, overshooting action potentials, comprising three components, occur. The first component in time is small and represents an excitatory synaptic potential for orthodromic stimulation or an axon spike (AS) for antidromic stimulation, electrotonically conducted into the soma. The second component is larger, being an electrotonically conducted integrating segment spike (ISS). The final component is the soma spike (SS). Neither AS nor ISS have a late positive phase, but there is a large, prolonged one for SS. The latter, combined with rapid accommodation, determine a low maximum firing rate for the neurons. Most nerves entering the ganglion make excitatory inputs onto each DUM neuron, which is readily driven to spike by electric excitation of either connective. There is a great deal of spontaneous excitatory synaptic input to each DUM neuron and a high proportion of it is common. Although there is no detectable electrical coupling between the cells, there is about 30% synchronous firing, apparently due to the common inputs; independent excitation and inhibition also occur. All sensory modalities tested have inputs to the neurons, which tend to fire constantly at a low rate (1 per 3–4 sec). In reflex actions, DUM neurons tend to fire before motor output occurs. It is suggested that the cells will be found to have many functions serving a general role comparable to that achieved by the release of adrenaline in vertebrates.     

Sharpness of Spike Initiation in Neurons Explained by Compartmentalization

In cortical neurons, spikes are initiated in the axon initial segment. Seen at the soma, they appear surprisingly sharp. A standard explanation is that the current coming from the axon becomes sharp as the spike is actively backpropagated to the soma. However, sharp initiation of spikes is also seen in the input–output properties of neurons, and not only in the somatic shape of spikes; for example, cortical neurons can transmit high frequency signals. An alternative hypothesis is that Na channels cooperate, but it is not currently supported by direct experimental evidence. I propose a simple explanation based on the compartmentalization of spike initiation. When Na channels are placed in the axon, the soma acts as a current sink for the Na current. I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage.     

Unit responses of the first and second somatosensory areas to stimulation of the ventroposterior thalamic nucleus

Single unit responses of the first (SI) and second (SII) somatosensory areas to stimulation of the ventroposterior thalamic nucleus (VP) were investigated in cats immobilized with D-tubocurarine. In response to VP stimulation 12.0% of reacting SI neurons and 9.5% of SII neurons generated an antidromic spike. In most antidromic responses of both SI and SII neurons the latent period did not exceed 1.0 msec. The minimal latent period of spike potentials during orthodromic excitation was 1.5 msec in SI and 1.7 msec in SII. Neurons with an orthodromic spike latency of not more than 3.0 msec were more numerous in SI than those with a latency of 3.1–4.5 msec. The ratio between the numbers of neurons of these two groups in SII was the opposite. In SII there were many more neurons with a latency of 5.6–8.0 msec than in SI. EPSPs appeared after a latent period of 1.1–9.0 msec in SI and of 1.4–6.6 msec in SII. The latent period of IPSPs was 1.5–6.8 msec in SI and 2.2–9.4 msec in SII. The relative importance of different pathways for excitatory and inhibitory influences of VP on SI and SII neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 2, pp. 115–121, March–April, 1976.     

A prolonged,voltage-dependent calcium permeability revealed by tetraethylammonium in the soma and axon of Aplysia giant neuron

The soma but not the axon of the giant neuron, R2, of Aplysia can generate an all-or-none Ca spike in Na-free or TTX-containing medium (Junge and Miller, 1974). Extracellular axonal recordings made at several distances from the soma provide evidence that the transition in ability to fire a spike in Na-free medium occurs within the first 250 μm of the axon. Application of 25 mM TEA-Br to the bathing medium causes a more than tenfold increase in the duration of the somatic action potential. The duration of the axonal action potential in TEA decreases with distance from the soma. At distances greater than 3 mm from the soma this concentration of TEA causes little or no increase in the duration of the axon spike. The effect of 25 mM TEA on both the soma and proximal axon is blocked reversibly by 30 mM CoCl₂ or 1 mM CdCl₂. The duration of the somatic action potential in TEA increases with an increase in Ca concentration of the bath. At a constant concentration of Na, the voltage level of the somatic plateau increases with Ca concentration in the manner predicted for a Ca electrode. In the presence of 11 mM Ca²⁺ the potential of the plateau is relatively insensitive to Na concentration. The TEA plateau in R2 reveals a prolonged voltage-dependent permeability to Ca. The duration of the plateau may indicate the degree of Ca activation during a spike.     

Depolarization of primary afferents during fictitious scratching in thalamic cats

The dorsal cord and dorsal root potentials were recorded in immobilized thalamic cats during fictitious scratching evoked by mechanical stimulation of the ear. Depolarization of primary afferents was shown to be simulated by the central scratching generator. Antidromic spike discharges appeared at the peak of the primary afferent depolarization waves in certain afferent fibers. Similar discharges arise in the resting state in response to stimulation of limb mechanoreceptors. It is suggested that during real scratching primary afferent depolarization and antidromic spikes evoked by it may effectively modulate the level of the afferent flow to spinal neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 2, pp. 173–176, March–April, 1978.     

Electrotonic interaction between secondary neurons of the carp olfactory bulb

Responses of secondary neurons of the carp olfactory bulb evoked by electrical stimulation of the olfactory tract were investigated by intracellular recording. In most neurons spike responses were identified as antidromic. Their latent periods varied from 2.5 to 55 msec. Two other types of responses of secondary neurons had constant latent periods: the pseudo-antidromic spike and a fast low-amplitude depolarization potential. It is concluded that these responses are generated by the antidromic spike of a neighboring neuron, connected electrotonically with the recorded neuron.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 490–496, September–October, 1976.