scholarly journals THE REFRACTORY STATE OF THE GENERATOR AND PROPAGATED POTENTIALS IN A PACINIAN CORPUSCLE

1958 ◽  
Vol 41 (4) ◽  
pp. 805-824 ◽  
Author(s):  
Werner R. Loewenstein ◽  
Rafael Altamirano-Orrego

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.

1958 ◽  
Vol 41 (6) ◽  
pp. 1245-1265 ◽  
Author(s):  
Werner R. Loewenstein ◽  
Raquel Rathkamp ◽  

The sensory nerve ending in the Pacinian corpuscle is surrounded by a non-nervous capsular structure which occupies about 99.9 per cent of the corpuscle's entire mass. After extirpation of practically all of the non-nervous structure, the sense organ's remains continue to function as a mechano-receptor, namely to produce generator and all-or-nothing potentials in response to mechanical stimuli. Compression of the first intracorpuscular node of Ranvier abolishes the production of "all-or-nothing" potentials in the corpuscle. Graded generator potentials constitute then the only response to mechanical stimulation. This reveals that the first node is the site of origin of the all-or-nothing potential and that the non-myelinated ending is incapable of producing all-or-nothing responses in response to mechanical stimulation. Compression of the entire length of non-myelinated ending suppresses the production of generator potentials. Partial compression of the ending abolishes mechano-responsiveness only of the compressed part. The intact remains of the ending continue to give generator potentials upon mechanical stimulation. This suggests that the generator potential arises at functionally independent membrane parts distributed all over the non-myelinated nerve ending. 24 to 36 hours after denervation of the corpuscle by transection of its sensory axon, no sign of electric activity is detected. Failure of mechano-reception at the nerve ending precedes that of conduction at the degenerating myelinated axon.


1960 ◽  
Vol 43 (5) ◽  
pp. 981-998 ◽  
Author(s):  
W. R. Loewenstein ◽  
N. Ishiko

It has previously been shown that the site of production of the generator potential in Pacinian corpuscles is the receptor membrane of the non-myelinated ending, and the site of initiation of the nerve impulse, the adjacent (first) Ranvier node. Effects of membrane polarization of these sites were studied in the present work. Nerve ending and first Ranvier node were isolated by dissection, electric activity was recorded from, and polarizing currents were passed through them. All observations were done at steady levels of polarization, seconds after onset of current flow. The following results were obtained: The amount of charge transferred through the excited receptor membrane is a function of the electrical gradients across the membrane. The generator potential in response to equal mechanical stimuli increases with resting potential of the receptor membrane. The refractory state of the generator potential is not affected by polarization. The electrical threshold for impulse firing at the first Ranvier node (measured by the minimal amplitude of generator potential which elicits a nodal impulse) is nearly minimal at normal resting potential of the node. Both, hyperpolarization and depolarization lead to a rise in nodal threshold. For any level of polarization of nodal and receptor membrane, the threshold for production of impulses by adequate (mechanical) stimulation appears determined by the generator potential-stimulus strength relation and by the electrical threshold of the node.


1958 ◽  
Vol 41 (4) ◽  
pp. 847-856 ◽  
Author(s):  
Werner R. Loewenstein

A period of supernormal excitability is left by a propagated impulse in a Pacinian corpuscle. The increase in excitability is found 6 to 10 msec. after an impulse occurs in the corpuscle. Supernormality is produced by either mechanically elicited dromic impulses, or by electrically excited antidromic impulses. Generator potentials do not cause supernormality. Local potentials discharged spontaneously by the corpuscle, and which fall on the supernormal trail left by an antidromic impulse, become enhanced in amplitude, an eventually are turned into propagated dromic potentials. The supernormal period is interpreted as caused by a negative after-potential left at the first intracorpuscular node of Ranvier which outlasts both the recovery time of the firing level and that of the generator potential during the corpuscle's relative refractory period.


2016 ◽  
Vol 30 (4) ◽  
pp. 141-154 ◽  
Author(s):  
Kira Bailey ◽  
Gregory Mlynarczyk ◽  
Robert West

Abstract. Working memory supports our ability to maintain goal-relevant information that guides cognition in the face of distraction or competing tasks. The N-back task has been widely used in cognitive neuroscience to examine the functional neuroanatomy of working memory. Fewer studies have capitalized on the temporal resolution of event-related brain potentials (ERPs) to examine the time course of neural activity in the N-back task. The primary goal of the current study was to characterize slow wave activity observed in the response-to-stimulus interval in the N-back task that may be related to maintenance of information between trials in the task. In three experiments, we examined the effects of N-back load, interference, and response accuracy on the amplitude of the P3b following stimulus onset and slow wave activity elicited in the response-to-stimulus interval. Consistent with previous research, the amplitude of the P3b decreased as N-back load increased. Slow wave activity over the frontal and posterior regions of the scalp was sensitive to N-back load and was insensitive to interference or response accuracy. Together these findings lead to the suggestion that slow wave activity observed in the response-to-stimulus interval is related to the maintenance of information between trials in the 1-back task.


A preparation of a single Pacinian corpuscle in the cat’s mesentery has been used to study the initiation of nerve impulses in sensory endings. The minimum movement of a mechanical stimulator required to excite a single corpuscle has been found to be 0⋅5 μ in 100 μ sec. It has been difficult to produce repetitive discharges with rectangular pulses of long duration, either mechanical or of constant current. The latency between a mechanical stimulus and the initiation of an impulse has a value around 1⋅5 msec, for threshold stimuli, and this decreases to a minimum value around 0⋅5 msec, as the stimulus is increased; it is altered only slightly, if at all, by changes in the duration of the maintained displacement of the mechanical stimulator. Subthreshold mechanical stimuli have been shown to facilitate stimulation by electrical test shocks. The return of excitability at the ending is independent of the nature of the conditioning stimulus and varies but little with the nature of the test shock. The value of the latency at threshold is unaffected by the relatively refractory state. The relations of these results to various hypotheses are discussed, and it is suggested that these results can all be accounted for in terms of the known properties of axons.


1958 ◽  
Vol 41 (4) ◽  
pp. 825-845 ◽  
Author(s):  
Werner R. Loewenstein

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.


Like the axolemma of the giant nerve fibre of the squid, the nodal membrane of frog myelinated nerve fibres after blocking transmembrane ionic currents exhibits asymmetrical displacement currents during and after hyperpolarizing and depolarizing voltage clamp pulses of equal size. The steady-state distribution of charges as a function of membrane potential is consistent with Boltzmann’s law (midpoint potential —33.7 mV; saturation value 17200 charges/(μm 2 ). The time course of the asymmetry current and the voltage dependence of its time constant are consistent with the notion that due to a sudden change in membrane potential the charges undergo a first order transition between two configurations. Size and voltage dependence of the time constant are similar to those of the activation of the sodium conductance assuming m 2 h kinetics, The results suggest the presence of ten times more sodium channels (5000/μm2) in the node of Ranvier than in the squid giant axon with similar sodium conductance per channel (2-3 pS),


2006 ◽  
Vol 80 (18) ◽  
pp. 9171-9180 ◽  
Author(s):  
Cristina Barreca ◽  
Peter O'Hare

ABSTRACT Herpes simplex virus (HSV) normally undergoes productive cytocidal infection in culture and is thought of as relatively resistant to innate immune responses such as interferon. We previously described an unusual pattern of infection in culture in MDBK cells, which after initial productive infection, surprisingly resulted in progressive suppression of replication and cell recovery. The dominance of the refractory state was due to the inability to suppress interferon production and subsequent paracrine signaling. Here, using a wild-type HSV-1 strain expressing green fluorescent protein (GFP)-VP16, we analyze aspects of long-term HSV persistence resulting from this oscillating refractory state. We show that the gradual suppression of GFP-VP16 expression correlated with a biphasic pattern of accumulation of viral DNA and extracellular virus titers. We quantify virus maintenance in a minor subpopulation of cells during subculture, show the reemergence of virus by infectious center assay, and demonstrate that this required intracellular events over a 24- to 48-h time course. We also demonstrate that conditioned medium (cMed) from infected cells induced a profound shutoff of HSV gene expression at the transcriptional level. Finally, we demonstrate that this suppression was extremely rapid, requiring only 1 h of treatment to essentially abolish HSV immediate-early expression, and surprisingly persisted for almost 2 days after removal of the cMed. These combined effects underpin the oscillating effect both in plaque progression, where infection spreads but is overwhelmed by the accumulation of inhibitory components, enabling cell recovery, and virus maintenance in a subpopulation of cells. These results may be relevant to consider in studies of HSV latency in different animal models.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Masashi Kameda ◽  
Shogo Ohmae ◽  
Masaki Tanaka

Rhythmic events recruit neuronal activity in the basal ganglia and cerebellum, but their roles remain elusive. In monkeys attempting to detect a single omission of isochronous visual stimulus, we found that neurons in the caudate nucleus showed increased activity for each stimulus in sequence, while those in the cerebellar dentate nucleus showed decreased activity. Firing modulation in the majority of caudate neurons and all cerebellar neurons was proportional to the stimulus interval, but a quarter of caudate neurons displayed a clear duration tuning. Furthermore, the time course of population activity in the cerebellum well predicted stimulus timing, whereas that in the caudate reflected stochastic variation of response latency. Electrical stimulation to the respective recording sites confirmed a causal role in the detection of stimulus omission. These results suggest that striatal neurons might represent periodic response preparation while cerebellar nuclear neurons may play a role in temporal prediction of periodic events.


1979 ◽  
Vol 73 (6) ◽  
pp. 685-702 ◽  
Author(s):  
W T Clusin ◽  
M V Bennett

Tonic nerve activity in skate electroreceptors is thought to result from spontaneous activity of the lumenal membranes of the receptor cells which is modulated by applied stimuli. When physiological conditions are simulated in vitro, the receptor epithelium produces a current which flows inward across the lumenal surface. This epithelial current exhibits small spontaneous sinusoidal fluctuations about the mean that are associated with corresponding but delayed fluctuations in postsynaptic response. Small voltage stimuli produce damped oscillations in the epithelial current similar in time-course to the spontaneous fluctuations. For lumen-negative, excitatory stimuli, these responses are predominantly an increase over the mean inward current. For inhibitory stimuli they are predominantly a decrease. Increased inward current across the lumenal membranes of the receptor cells increases depolarization of the presynaptic membranes in the basal faces leading to increased release of transmitter and an excitatory postsynaptic response. Decreased inward current decreases depolarization of the presynaptic membranes leading to a reduction in transmitter release and an inhibitory postsynaptic response. Clear changes in postsynaptic response are detectable during stimuli as small as 5 microV with saturation occurring at +/- 400 microV. The evoked oscillations in epithelial current are damped and the postsynaptic responses decline during maintained stimuli with large off-responses occurring at stimulus termination. The initial peak of the off-response is similar to the response produced by onset of an oppositely directed stimulus. These observations substantiate the role of receptor cell excitability in the detection of small voltage changes.


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