Generator processes of repetitive activity in a pacinian corpuscle

Response patterns resulting from repetitive mechanical stimulation of the corpuscle depend on (1) the time course of recovery of the generator potential, on (2) the recovery of critical firing height, and on (3) the stimulus strength/generator potential function. By either augmenting stimulus frequency at constant strength, or by reducing strength at constant frequency, a sequence of propagated potentials is turned into a pattern of alternating regenerative and generator responses. In such a pattern an extra impulse can be set up whenever an extra stimulus produces a generator potential of enough amplitude to reach the firing height of the corresponding period. The new requirements of firing height introduced by the refractory trail of the extra impulse determine resetting of periodicity and appearance of a "compensatory pause." The decay time of the single generator potential is independent of stimulus duration. This is interpreted as a factor determining receptor adaptation. Upon repetitive stimulation at intervals above ½ decay time of the single generator potential, a compound generator potential is built up which shows no spontaneous decline. However, in spite of being considerably greater than the firing height for single impulses, the constant level of depolarization of the compound generator potential is unable to produce propagated potentials. A hypothesis is brought forward which considers the generator potential to arise from membrane units with fluctuating excitability scattered over the non-myelinated nerve ending.     

The refractory state of the generator and propagated potentials in a pacinian corpuscle

A propagated potential produced in the Pacinian corpuscle in response to mechanical stimuli leaves a refractory state of 7 to 10 msec. duration. The refractory state is presumably produced at the first intracorpuscular node of Ranvier. The recovery of receptor excitability for producing an all-or-none response to mechanical stimulation follows the same time course as that of the electrically excited axon. Upon progressive reduction of stimulus interval (mechanical), the propagated potential falls progressively to 75 per cent of its resting magnitude and becomes finally blocked within the corpuscle. A non-propagated all-or-none potential, presumably corresponding to activity of the first node, is then detected. The critical firing level for all-or-none potentials increases progressively during the relative refractory period of the all-or-none potential, as the stimulus interval is shortened. Thus generator potentials up to 85 per cent of a propagated potential can be produced in absence of all-or-none activity. Generator potentials show: gradual over-all increase in amplitude and rate of rise as a function of stimulus strength; constant latency; and spontaneous fluctuations in amplitude. A generator potential leaves a refractory state (presumably at the non-myelinated ending) so that the amplitude of a second generator response which falls on its refractory trail is directly related to the time elapsed after the first generator response and inversely to its amplitude. The generator potential develops independently of any refractory state left by a preceding all-or-none potential.     

Electrical Characteristics of Insect Mechanoreceptors

External direct coupled recordings from the neurons of the mechanosensory hairs of insects show nerve impulses and graded slow potentials in response to deformation of the hair. These slow potentials or receptor potentials are negative going, vary directly with the magnitude of the stimulus, and show no overshoot when returning to baseline. The impulses have an initial positive phase which varies in size directly with the amplitude of the receptor potential. The receptor potential is related to the generator potential for the impulse in that it must attain some critical level before impulses are produced, and the frequency of impulses varies directly with amplitude of the receptor potential. The receptor potential does not return to the baseline after each impulse. In some receptors static deformation of the hair will maintain the receptor potential. It appears likely that both the receptor potential and the variation in size of the impulses are caused by a change in conductance of the cell membrane at the receptor site, and that the receptor potential originates at a site which is not invaded by the propagated impulses.     

II. Post-Tetanic Potentiation and Depression of Generator Potential in a Single Non-Myelinated Nerve Ending

Repetitive activity at the non-myelinated ending of Pacinian corpuscles leaves the following after-effects: (1) With certain parameters of repetitive mechanical stimulation of the ending a depression in generator potential is produced. The effect is fully reversible and has low energy requirements. The effect is a transient decrease in responsiveness of the receptor membrane which is unrelated to changes in resting membrane potential. It appears to reflect an inactivation process of the receptor membrane. Within certain limits, the depression increases as a function of strength, frequency, and train duration of repetitive stimuli. (2) With other, more critical parameters of repetitive stimulation a hyperpolarization of the ending and of the first intracorpuscular Ranvier node may be produced. This leads to respectively post-tetanic potentiation of generator potential and increase in nodal firing threshold. The balance of these after-effects determines the threshold for the production of nerve impulses by adequate (mechanical) stimulation of the sense organ. The after-effects of activity at the node can be elicited by dromic (mechanical) stimulation of the ending, as well as by antidromic (electric) stimulation of the axon; the after-effects at the ending can only be produced by dromic and not by antidromic stimulation.     

Excitability changes in the crustacean motor axon following activity

It has been shown experimentally that the crustacean motor axon is supernormally excitable following a train of action potentials (Zucker 1974). Such a phenomenon can lead to recruitment of terminals which are unexcited at low rates of stimulation. Although currents underlying the crustacean motor axon have been characterized (Connor et al. 1977), it is not known whether this membrane model accounts for a supernormal period, what might cause superexcitablity in this model, or how excitability might change during repetitive stimulation. In present study, it is demonstrated that the crustacean motor axon model does predict a supernormal period, that the supernormal period results from slow recovery from inactivation of the transient potassium, or A, current, and that supernormal excitability is enhanced by repetitive stimulation.     

Synaptic inhibition in an isolated nerve cell

Following the preceding studies on the mechanisms of excitation in stretch receptor cells of crayfish, this investigation analyzes inhibitory activity in the synapses formed by two neurons. The cell body of the receptor neuron is located in the periphery and sends dendrites into a fine muscle strand. The dendrites receive innervation through an accessory nerve fiber which has now been established to be inhibitory. There exists a direct peripheral inhibitory control mechanism which can modulate the activity of the stretch receptor. The receptor cell which can be studied in isolation was stimulated by stretch deformation of its dendrites or by antidromic excitation and the effect of inhibitory impulses on its activity was analyzed. Recording was done mainly with intracellular leads inserted into the cell body. 1. Stimulation of the relatively slowly conducting inhibitory nerve fiber either decreases the afferent discharge rate or stops impulses altogether in stretched receptor cells. The inhibitory action is confined to the dendrites and acts on the generator mechanism which is set up by stretch deformation. By restricting depolarization of the dendrites above a certain level, inhibition prevents the generator potential from attaining the "firing level" of the cell. 2. The same inhibitory impulse may set up a postsynaptic polarization or a depolarization, depending on the resting potential level of the cell. The membrane potential at which the inhibitory synaptic potential reverses its polarity, the equilibrium level, may vary in different preparations. The inhibitory potentials increase as the resting potential is displaced in any direction from the inhibitory equilibrium. 3. The inhibitory potentials usually rise to a peak in about 2 msec. and decay in about 30 msec. After repetitive inhibitory stimulation a delayed secondary polarization phase has frequently been seen, prolonging the inhibitory action. Repetitive inhibitory excitation may also be followed by a period of facilitation. Some examples of "direct" excitation by the depolarizing action of inhibitory impulses are described. 4. The interaction between antidromic and inhibitory impulses was studied. The results support previous conclusions (a) that during stretch the dendrites provide a persisting "drive" for the more central portions of the receptor cell, and (b) that antidromic all-or-none impulses do not penetrate into the distal portions of stretch-depolarized dendrites. The "after-potentials" of antidromic impulses are modified by inhibition. 5. Evidence is presented that inhibitory synaptic activity increases the conductance of the dendrites. This effect may occur in the absence of inhibitory potential changes.     

Further study of soma,dendrite, and axon excitation in single neurons

The present investigation continues a previous study in which the soma-dendrite system of sensory neurons was excited by stretch deformation of the peripheral dendrite portions. Recording was done with intracellular leads which were inserted into the cell soma while the neuron was activated orthodromically or antidromically. The analysis was also extended to axon conduction. Crayfish, Procambarus alleni (Faxon) and Orconectes virilis (Hagen), were used. 1. The size and time course of action potentials recorded from the soma-dendrite complex vary greatly with the level of the cell's membrane potential. The latter can be changed over a wide range by stretch deformation which sets up a "generator potential" in the distal portions of the dendrites. If a cell is at its resting unstretched equilibrium potential, antidromic stimulation through the axon causes an impulse which normally overshoots the resting potential and decays into an afternegativity of 15 to 20 msec. duration. The postspike negativity is not followed by an appreciable hyperpolarization (positive) phase. If the membrane potential is reduced to a new steady level a postspike positivity appears and increases linearly over a depolarization range of 12 to 20 mv. in various cells. At those levels the firing threshold of the cell for orthodromic discharges is generally reached. 2. The safety factor for conduction between axon and cell soma is reduced under three unrelated conditions, (a) During the recovery period (2 to 3 msec.) immediately following an impulse which has conducted fully over the cell soma, a second impulse may be delayed, may invade the soma partially, or may be blocked completely. (b) If progressive depolarization is produced by stretch, it leads to a reduction of impulse height and eventually to complete block of antidromic soma invasion, resembling cathodal block, (c) In some cells, when the normal membrane potential is within several millivolts of the relaxed resting state, an antidromic impulse may be blocked and may set up within the soma a local potential only. The local potential can sum with a second one or it may sum with potential changes set up in the dendrites, leading to complete invasion of the soma. Such antidromic invasion block can always be relieved by appropriate stretch which shifts the membrane potential out of the "blocking range" nearer to the soma firing level. During the afterpositivity of an impulse in a stretched cell the membrane potential may fall below or near the blocking range. During that period another impulse may be delayed or blocked. 3. Information regarding activity and conduction in dendrites has been obtained indirectly, mainly by analyzing the generator action under various conditions of stretch. The following conclusions have been reached: The large dendrite branches have similar properties to the cell body from which they arise and carry the same kind of impulses. In the finer distal filaments of even lightly depolarized dendrites, however, no axon type all-or-none conduction occurs since the generator potential persists to a varying degree during antidromic invasion of the cell. With the membrane potential at its resting level the dendrite terminals contribute to the prolonged impulse afternegativity of the soma. 4. Action potentials in impaled axons and in cell bodies have been compared. It is thought that normally the over-all duration of axon impulses is shorter. Local activity during reduction of the safety margin for conduction was studied. 5. An analysis was made of high frequency grouped discharges which occasionally arise in cells. They differ in many essential aspects from the regular discharges set up by the generator action. It is proposed that grouped discharges occur only when invasion of dendrites is not synchronous, due to a delay in excitation spread between soma and dendrites. Each impulse in a group is assumed to be caused by an impulse in at least one of the large dendrite branches. Depolarization of dendrites abolishes the grouped activity by facilitating invasion of the large dendrite branches.     

Responses of motoneurons undergoing chromatolysis

The delayed and asynchronous firing of chromatolytic motoneurons in response to group I afferent volleys is shown to be evoked monosynaptically, there being an abnormally long and variable delay between onset of monosynaptic action and generation of impulse discharge. Intensity of monosynaptic excitatory action is reduced, and considerable variability in the form of successively evoked postsynaptic potentials is often observed. No evidence has been found for the development of excitatory group I polysynaptic pathways. Reduction in responsiveness of finer dendrites is indicated by the feeble "d" response evoked by an antidromic volley in a chromatolytic motor nucleus. Antidromic impulses appear to invade the cell bodies and coarse dendrites, but die out at points short of the normal extent of dendritic invasion. Vigorous firing of Renshaw cells can be elicited by antidromic volleys. Chromatolytic motoneurons appear to maintain reasonably normal resting membrane potentials, but are more susceptible to damage than are normal cells. Action potentials are large and usually overshoot the resting potential level. Post spike potentials are similar to those of normal cells except for a less prominent, or absent, early phase of depolarisation. In contrast with the reduced responsiveness of peripheral dendrites, there is a lowered threshold for antidromic and segmental reflex synaptic activation of the more central regions, probably the cell bodies and nearby coarse dendrites, of motoneurons undergoing chromatolysis.     

Multiple spike initiation zones in a neuron implicated in learning in the leech: a computational model

Sensitization of the defensive shortening reflex in the leech has been linked to a segmentally repeated tri-synaptic positive feedback loop. Serotonin from the R-cell enhances S-cell excitability, S-cell impulses cross an electrical synapse into the C-interneuron, and the C-interneuron excites the R-cell via a glutamatergic synapse. The C-interneuron has two unusual characteristics. First, impulses take longer to propagate from the S soma to the C soma than in the reverse direction. Second, impulses recorded from the electrically unexcitable C soma vary in amplitude when extracellular divalent cation concentrations are elevated, with smaller impulses failing to induce synaptic potentials in the R-cell. A compartmental, computational model was developed to test the sufficiency of multiple, independent spike initiation zones in the C-interneuron to explain these observations. The model displays asymmetric delays in impulse propagation across the S–C electrical synapse and graded impulse amplitudes in the C-interneuron in simulated high divalent cation concentrations.     

The generation of action potentials in the terminals of the Schaffer collaterals during long-term potentiation in the CA1 region of the hippocampus]

Experiments were performed in rat hippocampal slices. Activity of individual CA3 pyramidal neurons and field potentials in the CA1 areas were recorded extracellularly. The collision technique was applied to detect the antidromic origin of the background action potentials in the somata of CA3 neurons. Threshold stimulation of terminals of the Schaffer collaterals in the stratum radiatum of the CA1 area was applied to study their excitability during the CA1 long-term potentiation. During the long-term potentiation, antidromic action potentials appeared in the somata of the CA3 neurons. The obtained evidence suggests that the synaptic potentiation is accompanied by an enhancement of axon terminal excitability resulting in generation of the action potentials.     

Digital Computer Solutions for Excitation and Propagation of the Nerve Impulse

The Hodgkin-Huxley model of the nerve axon describes excitation and propagation of the nerve impulse by means of a nonlinear partial differential equation. This equation relates the conservation of the electric current along the cablelike structure of the axon to the active processes represented by a system of three rate equations for the transport of ions through the nerve membrane. These equations have been integrated numerically with respect to both distance and time for boundary conditions corresponding to a finite length of squid axon stimulated intracellularly at its midpoint. Computations were made for the threshold strength-duration curve and for the repetitive firing of propagated impulses in response to a maintained stimulus. These results are compared with previous solutions for the space-clamped axon. The effect of temperature on the threshold intensity for a short stimulus and for rheobase was determined for a series of values of temperature. Other computations show that a highly unstable subthreshold propagating wave is initiated in principle by a just threshold stimulus; that the stability of the subthreshold wave can be enhanced by reducing the excitability of the axon as with an anesthetic agent, perhaps to the point where it might be observed experimentally; but that with a somewhat greater degree of narcotization, the axon gives only decrementally propagated impulses.     

Excitability Changes of the Mauthner Cell during Collateral Inhibition

Excitability changes during collateral inhibition of the goldfish Mauthner cell (M cell) were measured directly by stimulating the cell with current pulses applied through an intracellular electrode. Excitability was suppressed during the extrinsic hyperpolarizing potential (EHP) as well as during the collateral IPSP. The inhibitory effect of the EHP was shown to be comparable in intensity to the effect of the IPSP. Excitability changes in the M cell during collateral IPSP depended on changes in the membrane conductance as well as in the membrane potential. Some simple equations are advanced which describe the excitability change during the IPSP in terms of changes in membrane potential and conductance. It was also found that invasion of antidromic impulses into the M cell was suppressed during the EHP, but not during the collateral IPSP. Conductance increase during the IPSP did not interfere with the invasion of antidromic impulses.     

In Vivo Studies on Fast and Slow Muscle Fibers in Cat Extraocular Muscles

In anesthetized in vivo preparations, responses of two types of extraocular muscle fibers have been studied. The small, multiply innervated slow fibers have been shown to be capable of producing propagated impulses, and thus have been labeled slow multi-innervated twitch fibers. Fast and slow multi-innervated twitch fibers are distinguished by impulse conduction velocities, by ranges of membrane potentials, by amplitudes and frequencies of the miniature end plate potentials, by responses to the intravenous administration of succinylcholine, by the frequency of stimulation required for fused tetanus, and by the velocities of conduction of the nerve fibers innervating each of the muscle fiber types.     

Physiology of Photoreceptor Neurons in the Abdominal Nerve Cord of the Crayfish

Nerve fibers which respond to illumination of the sixth abdominal ganglion were isolated by fine dissection from connectives at different levels in the abdominal nerve cord of the crayfish. Only a single photosensitive neuron is found in each connective; its morphological position and pattern of peripheral connections are quite constant from preparation to preparation. These cells are "primary" photoreceptor elements by the following criteria: (1) production of a graded depolarization upon illumination and (2) resetting of the sensory rhythm by interpolated antidromic impulses. They are also secondary interneurons integrating mechanical stimuli which originate from appendages of the tail. Volleys in ipsilateral afferent nerves produce short-latency graded excitatory postsynaptic potentials which initiate discharge of one or two impulses; there is also a higher threshold inhibitory pathway of longer latency and duration. Contralateral afferents mediate only inhibition. Both inhibitory pathways are effective against both spontaneous and evoked discharges. In the dark, spontaneous impulses arise at frequencies between 5 and 15 per second with fairly constant intervals if afferent roots are cut. Since this discharge rhythm is reset by antidromic or orthodromic impulses, it is concluded that an endogenous pacemaker potential is involved. It is postulated that the increase in discharge frequency caused by illumination increases the probability that an inhibitory signal of peripheral origin will be detected.     

Electrical signs of impulse conduction in spinal motoneurons

An analysis has been made of the electrical responses recorded on the surface and within the substance of the first sacral spinal segment when the contained motoneurons are excited by single and repeated antidromic ventral root volleys. A succession of negative deflections, designated in order of increasing latency m, i, b, d, has been found. Each of those deflections possesses some physiological property or properties to distinguish it from the remainder. Indicated by that fact is the conclusion that the successive deflections represent impulse conduction through successive parts of the motoneurons that differ in behavior, each from the others. Since the spinal cord constitutes a volume conductor the negative deflections are anteceded by a positive deflection at all points except that at which the axonal impulses first enter from the ventral root into the spinal cord. Frequently two or more negative deflections are recorded together in overlapping sequence, but for each deflection a region can be found in which the onset of that deflection marks the transition from prodromal positivity to negativity. Deflection m is characteristic of axonal spikes. Latent period is in keeping with known axonal conduction velocity. Refractory period is brief. The response represented by m is highly resistant to asphyxia. Maximal along the line of ventral root attachment and attenuating sharply therefrom, deflection m can be attributed only to axonal impulse conduction. Deflection i is encountered only within the cord, and is always associated with a deflection b. The i,b complex is recordable at loci immediately dorsal to regions from which m is recorded, and immediately ventral to points from which b is recorded in isolation from i. Except for its great sensitivity to asphyxia, deflection i has properties in common with those of m, but very different from those of b or d. To judge by properties i represents continuing axonal impulse conduction into a region, however, that is readily depolarized by asphyxia. Deflection b possesses a unique configuration in that the ascending limb is sloped progressively to the right indicating a sharp decrease in velocity of the antidromic impulses penetrating the b segment. A second antidromic volley will not conduct from i segment to b segment of the motoneurons unless separated from the first by nearly 1 msec. longer than is necessary for restimulation of axons. This value accords with somatic refractoriness determined by other means. Together with spatial considerations, the fact suggests that b represents antidromic invasion of cell bodies. Deflection d is ubiquitous, but in recordings from regions dorsal and lateral to the ventral horn, wherein an electrode is close to dendrites, but remote from other segments of motoneurons, d is the initial negative deflection. In latency d is variable to a degree that demands that it represent slow conduction through rather elongated structures. When associated with deflection b, deflection d may arise from the peak of b with the only notable discontinuity provided by the characteristically sloped rising phase of b. Deflection d records the occupation by antidromic impulses of the dendrites. Once dendrites have conducted a volley they will not again do so fully for some 120 msec. Embracing the several deflections, recorded impulse negativity in the motoneurons may endure for nearly 5 msec. When the axonal deflection m is recorded with minimal interference from somatic currents, it is followed by a reversal of sign to positivity that endures as long as impulse negativity can be traced elsewhere, demonstrating the existence of current flow from axons to somata as the latter are occupied by impulses. Note is taken of the fact that impulse conduction through motoneurons is followed by an interval, measurable to some 120 msec., during which after-currents flow. These currents denote the existence in parts of the intramedullary motoneurons of after-potentials the courses of which must differ in different parts of the neurons, otherwise nothing would be recorded. The location of sources and sinks is such as to indicate that a major fraction of the current flows between axons and somata. For approximately 45 msec. the direction of flow is from dendrites to axons. Thereafter, and for the remaining measurable duration, flow is from axons to dendrites.     

Centrifugal effects on amacrine cells in the frog's retina

The effect of electrical stimulation of the optic nerve on various cells in the frog's retina was investigated by two methods: by the histochemical method (measurement of the amount of RNA in separate cells), and by intracellular recording of potentials. Rhythmic (5 per sec) stimulation of the nerve induced an increase in the amount of RNA in ganglion cells, and especially in amacrine cells. The level of RNA in bipolar and horizontal cells did not change. The results of the experiment indicate that in frogs (as in birds) centrifugal effects are produced through amacrine cells. In electrophysiological experiments reactions to stimulation of the nerve were manifested only in ganglion and amacrine cells. In the ganglion cells that was an antidromic impulse, but sometimes also a delayed impulse, which was evidently the result of secondary excitation of the cell. In amacrine cells the response consisted of a short excitant postsynaptic potential with a discharge of impulses superimposed on it. Data are presented indicating the existence of amacrine cells of different types, probably fulfilling different functions.Institute of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 3, pp. 293–300, May–June, 1971.     

Reflection of the plastic properties of 2 neurons with a common monosynaptic input in the statistical characteristics of their impulse activity

Changes of cross-correlation histograms (CCH) of impulse trains and of mean interspike intervals (ISI) of neurones N1 and N2 with a common monosynaptic excitatory or inhibitory-excitatory input from N3, at changes of efficiency of interneuronal connections, neurone excitability and summate action on them of independent random afferent synaptic inflows were studied by methods of mathematical and biomathematical modelling of neuronal interaction. It was shown that the increase of amplitude of the central peak (trough) of a normalized CCH of N1-N2 accompanied by reduction of mean ISI of N1 and N2, is either a sign of an increase of the amplitude of postsynaptic potentials of N1 and N2 elicited by impulses of the nonrecorded N3 or a sign of an increase of mean ISI of N3.     

Effect of a volatile anesthetic upon presynaptic excitability in mammalian hippocampus

Changes in presynaptic terminal axon excitability produced by enflurane in the rat hippocampal slice preparation were investigated by stimulation of Schaeffer collateral terminal axons and by recording single unit antidromic action potentials. Stimulating pulses were preceded by conditioning hyperpolarizing or depolarizing current pulses. A plot of net threshold for action potential generation against the conditioning pulse yields an "accommodation curve;" changes in this curve can be used to assess the mechanism by which changes in excitability are produced. Enflurane, at a concentration equivalent to approximately equal to 1.3 times the minimum alveolar concentration, reduced excitability of terminal axons and increased accommodation in a manner consistent with a possible change in the inactivation of gNa.     

Excitability of septo-hippocampal axon terminals: changes as a function of the level of neuronal activity

The septo-hippocampal terminals were electrically stimulated at the level of the gyrus dentatus in urethane anesthetized rats and antidromic responses were recorded in the medial septum. The excitability of the terminals was assessed by the threshold of terminal antidromic activation. An increase in the discharge frequency of the septal neurons following a microiontophoretic application of glutamate to their soma induced an increase in the antidromic activation threshold, i.e. a decrease in excitability of the terminals. An application of GABA which inhibited septal neuronal activity, induced a decrease in the antidromic activation threshold, i.e. an increase in the terminal excitability of septo-hippocampal neurons. These results are discussed in the light of the presynaptic autoreceptor hypothesis.     

Potentials of spinal motoneurons in cats with experimental tetanus

Potentials of motoneurons of the lower segments of the spinal cord were recorded with the aid of intracellular microelectrodes in experiments on cats with induced tetanus produced by injection of tetanus toxin (1500–2000 mouse LD₅₀) into the extensor muscles of the left shin. Neither afferent volleys of impulses in cutaneous and muscle nerves, nor antidromic volleys in the corresponding ventral roots, produced IPSPs in motoneurons of the extremity into which toxin was injected. The form both of antidromic peak potentials and of monosynaptic EPSPs in motoneurons in which IPSPs were blocked by tetanus toxin did not differ from the form of corresponding potentials of motoneurons in normal cats. The values of threshold depolarization for peak discharges during synaptic and direct stimulation were equal in tetanus and control motoneurons. Resistance and time constant values of the membrane in "tetanus" motoneurons did not differ from the corresponding values for "control" motoneurons.N. I. Pirogov Second Medical Institute, Moscow. Translated from Neirofiziologiya, Vol. 1, No. 1, pp. 25–34, July–August, 1969.