Facilitation of reactions of cortical neurons to cortical and peripheral stimulation after tetanization of the brain surface

The electrical activity of neurons of the sensomotor cortex of an unanesthetized rabbit was investigated. Conditioning tetanization of the cortex was carried out through surface electrodes located close to the site of the lead. Test stimuli were supplied through electrodes 2.5–12 mm more caudally on the cortical surface. In addition, peripheral test stimuli were applied. Impulse reactions to previously ineffective stimuli develop after conditioning tetanization and prolonged (up to 1 min) intensification of exciting postsynaptic potentials (EPSP) to cortical and peripheral test stimuli is observed. Facilitation of the reactions is especially clear during tetanization superthreshold for evoking epileptiform afterdischarges. It continued after the conclusion of these discharges and could also be observed during tetanization subthreshold for evoking afterdischarges. The time course of the facilitation was similar to the time course of the post-tetanic intensification of reactions of single stimuli applied with the electrodes used for tetanization. An analysis of the changes in intracellular activity makes it possible to assume that the mechanism of post-tetanic potentiation (PTP) lies at the basis of the described facilitation, which is considered as the "cellular analog" of the dominant focus which develops as a result of tetanization of the cortical surface.Institute of the Brain, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 3–12, January–February, 1971.     

Effect of local polarization of after-discharges of cortical neurones

After strong tetanization epileptiform after-discharges occur in the neurones of the sensorimotor cortex of unanaesthetized rabbits, they take the form of bursts of impulses occurring at intervals of 150–600 msec. The bursts are caused by paroxysmal depolarization shifts (PDS) of the membrane potential (MP). When the MP is reduced to 10–20 mV, on account of the considerable damage to the neurone the PDS give way to hyperpolarization oscillations. Unlike the prolonged action potentials (AP), which are quite frequently recorded in damaged cells, the intracellular PDS and the extracellular bursts of after-discharges show no change in frequency when a current is passed through the recording microelectrode. It was found impossible to suppress the generation of PDS by means of a hyperpolarizing current (1–3·10^–9 A), or to evoke PDS by a depolarizing current. Therefore we were unable to confirm the hypothesis that PDS occur as a result of reorganization of the generation of the electrical impulse. Support is given to the hypothesis that the PDS are altered and enormously potentiated excitatory postsynaptic potentials (EPSP)Brain Institute, Academy of Medical Sciences of the USSR, Moscow, Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 460–468, September–October, 1970.     

Protracted depolarizing potentials of neurons in a strychninized cortical slab isolated from the cat

Neuronal response in a cortical slab isolated from the cat during surface application of strychnine was investigated in experiments on immobilized unanesthetized animals by means of intracellular recording techniques. Protracted depolarizing potentials (PDP) were found to occur spontaneously and in response to a single intracortical electrical stimulus in a proportion of the neurons. These potentials could be triggered by transformation of response along the lines of "paroxysmal depolarizing shift" (PDS) — hyperpolarization, with hyperpolarization replaced by depolarizing potentials. A further increase in depolarizing after-potentials resulted in the generation of PDP. These changes were normally accompanied by enhanced summated epileptiform activity in the isolated cortical slab. It is postulated that PDP were triggered by increased calcium conductance at the neuronal membrane during intensification of paroxysmal response in the isolated cortical slab.I. I. Mechnikov University, Odessa. Translated from Neirofiziologiya, Vol. 22, No. 1, pp. 19–23, January–February, 1990.     

Habituation of postsynaptic unit responses of the cat motor cortex to stimuli of different modalities

Habituation (extinction) of postsynaptic unit responses of the cat motor cortex to repetitive electrodermal, photic, acoustic, and combined bimodal stimulation was investigated by intracellular recording. Habituation was shown by a decrease in the number of spikes per grouped discharge and a decrease in the amplitude and duration of the EPSPs, and sometimes IPSPs, on repetition of the stimulus. The way in which the course of habituation depends on the modality and duration of stimulation (at a constant frequency of 1/sec) is examined. Habituation of postsynaptic responses to sensory stimuli is observed with neurons of different functional groups, namely identified neurons of pyramidal tract and unidentified neurons, some of which were evidently pyramidal neurons and interneurons. The hypothesis is put forward that the habituation of PSPs of the cortical neurons is based on processes taking place mainly at the subcortical level.A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 545–553, September–October, 1972.     

Changes in membrane potential and postsynaptic potentials evoked by strychnine in neocortical neurons

Intracellular responses of neurons of the suprasylvian fissure to intracortical stimulation before and during topical cortical strychnine application was studied in experiments on immobilized, unanesthetized cats (a local anesthetic was used). Untreated cortical neurons responded to intracortical stimulation with a monosynaptic excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). Application of strychnine evoked epileptiform population activity and paroxysmal depolarizations of neuronal membrane potentials (MPs), followed by hyperpolarization. Increased hyperpolarizations, and the prolonged duration of their summation were responsible for an increased MP and reduced or abolished tonic spike activity. Intracellular application (as a result of diffusion from the microelectrode) of ethyleneglycoltetraacetate (EGTA) that blocked the calcium-dependent potassium membrane conductance (gK(Ca)) abolished the hyperpolarization. The development of epileptiform activity was accompanied by reduction of the IPSP, and an increase in the monosynaptic EPSP. The role of gK(Ca) and postsynaptic inhibition in epileptogenesis is discussed.I. I. Mechnikov State University, Odessa. Translated from Neirofiziologiya, Vol. 24, No. 6, pp. 684–691, November–December, 1992.     

Direct cortical responses to electric stimulation with different frequencies in chronic experiments on dogs]

Direct cortical responses (DCR) to a series of electrical stimuli with a frequency of I to 50 per second with 10 to 20 pulses in each series were studied in chronic experiments on dogs. The nature of cortical responses differed, depending on stimulation parameters. As the stimulation frequency increased, the amplitude and number of late DCR components decreased, and with further increase of frequency, the early components decreased as well. The following types of responses were revealed: recruiting, intermittent and decremental. As the stimulation frequency increased all the three types of responses could be obtained in one and the same cortical point. Recruiting was not typical of high-amplitude and multi-component DCR with a long phase of depression of initial negativity and slightly pronounced short-term subsequent facilitation, while the intermittent type of response appeared at lower frequencies than in other dogs (5 to 10 per sec). A decremental type of response was observed in all the dogs at a stimulation frequency higher than 30 per sec. The duration of the series of after-discharges to a burst of electrical pulses depended on the pattern of the DCR to a single stimulus and on the intensity and frequency of stimulation. With similar parameters of stimulation, the greater the amplitude and the longer the duration of the slow negative DCR wave, the longer the period of after-discharges following a series of stimuli.     

Neuronal response in a strychninized cortical slab isolated from the cat

Intracellular response in neurons and glial cells of an isolated cortical slab to direct electrical stimulation of the slab following surface application of strychnine was investigated during experiments on immobilized unanesthetized cats. Strychnine induced single epileptiform discharges and after-discharges in the slab and in the neurons it contained in the form of large-scale paroxysmal depolarization shifts (PDS) in membrane potential (MP). Spontaneous summated epileptiform discharges and neuronal activity in the units examined were not very synchronized. Electrical stimulation induced generalized paroxysmal activity in the isolated slab. Neuronal PDS were accompanied by refractory periods, onset of which did not depend on MP level. Strychnine increased the number of neurons manifesting background activity in which action potentials were generated by rhythmic depolarizing MP waves of extrasynaptic origin. Epileptiform response in strychninized cortical isolated slabs to presentation of single stimuli is accompanied by major depolarization shifts in the MP of glial cells. Paroxysmal excitation is thought to be triggered in strychninized isolated cortical slabs by extrasynaptic factors and closely linked to altered concentration of extracellular potassium.I. I. Mechnikov University, Odessa. Translated from Neirofiziologiya, Vol. 22, No. 1, pp. 23–29, January–February, 1990.     

Peculiarities of orthodromic inhibition in pacemaker neurons in Helix pomatia

We used the intracellular recording method to study the effect of a group of nerves in the visceral complex on the activity of a pacemaking giantneuron located in the peripheral part of the visceral ganglion in a mollusk. Single excitations of the left and right pallial, the intestinal, and the anal nerves with electrical stimuli evoked similar responses, consisting of phases of rapid depolarization (duration 100 msec, amplitude 3–5 mV) and slower hyperpolarization (duration 400 msec, amplitude 5–8 mV). The excitation also had an aftereffect, which was expressed in inhibition of the background activity of the pacemaker for several seconds. The most interesting of the functional characteristics of that response was the effects of summation. With rhythmic excitation by stimuli of low frequency (0.5–1 c/sec) the result of summation was general hyperpolarization of the neuron and the appearance of giant inhibitory postsynaptic potentials (IPSP's) with an amplitude of 12–16 mV. With higher frequency of excitation (2–3 c/sec and upward) we observed depolarization replacing the hyperpolarization of the neuron, but IPSP's of large amplitude were absent. At the end of rhythmic excitation prolonged inhibition of the pacemaker's activity, lasting some minutes, occurred in all cases. This article discusses the possible mechanisms of that type of prolonged inhibition of the pacemaker's activity, the origin of the phases in biphasic responses, and the reasons for differences in the course of summation of biphasic postsynaptic potentials.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 426–433, July–August, 1971.     

Effects of Long-Lasting Afferent Activation on Segmental Reflex Responses in Albino Rats,and Modifications of These Effects by Thyroxine and 4-Aminopyridine

In albino rats, we studied the effects of long-lasting tetanization of the dorsal roots of the L ₅ (homosynaptic activation) and L ₄ (heterosynaptic activation) segments on reflex discharges in the L ₅ ventral root evoked by single stimulation of the dorsal root of the same segment. Tetanization trains consisted of 5,000 stimuli applied with frequencies of 10, 50, 100, or 300 sec^–1, and their effects were tested during 10 min. There were no long-term post-tetanic potentiation (PTP) of monosynaptic responses when low frequencies of homosynaptic tetanization (10 and 50 sec^–1) were used. In the case of higher frequencies, PTP was rather clear and long-lasting. Under conditions of heterosynaptic activation, there was no PTP. Facilitation of polysynaptic responses developed at all the frequencies of homosynaptic tetanization used; when heterosynaptic tetanization was applied, such facilitation (although weaker) was also observed. In rats treated with agents increasing the excitability of spinal neuronal systems, such as thyroxine and 4-aminopyridine, tetanization of the studied inputs evoked long-term depression (LTD) of both mono- and polysynaptic components of the reflex discharges instead of PTP. Probable mechanisms of postsynaptic changes in the segmental reflex responses are discussed.     

Quantal analysis of long-term posttetanic changes in minimal postsynaptic potentials of hippocampal slices in vitro

Minimal excitatory postsynaptic potentials (EPSP) were investigated in 13 neurons under single or double-pulse near-threshold microstimulation of the radial layer (Schaffer's collaterals) and stratum oriens in surviving hippocampal slices (area CA1) in guinea pigs. The amplitude of 23 EPSP (9 units; 12 pathways) rose after tetanization of Schaffer's collaterals over a 5–55 min period, taken as long-term potentiation (LTP). Statistical analysis conducted using four methods of quantal hypothesis based on a binomial approximation revealed an increase in mean quantal content (m) during LTP. The rise in quantal size was only statistically significant when using data obtained from a section of these methods (mainly for stretches of over 15 min following tetanization) and shows no correlation with intensity of LTP. The pronounced rise in m demonstrated using different methods matches data from experiments on intact animals and indicates a presynaptic location of the mechanisms underlying protracted persistence of residual tetanization lasting some tens of minutes.Institute for Brain Research, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany. Zoological Institute, Jagiellonian University, Cracow, Poland. Translated from Neirofiziologiya, Vol. 22, No. 6, pp. 752–761, November–December, 1990.     

Suppression of "fast" IPSP,superposed on "slow", as a possible cause of priming in murine hippocampus

Intra- and extracellular response in area CA1 to stimulation of two independent afferent inputs, one a priming or conditioned and the other a test or primed input (C1 and C2, respectively) were recorded in surviving murine hippocampal slices. Duration and amplitude of test field potentials (FP) and of excitatory postsynaptic potentials (EPSP), were measured, as well as amplitude of "fast" and "slow" components of inhibitory postsynaptic potentials or stimulation varying between 0 and 1 sec. Conditioning brought about an increase in the duration of FP, in duration and amplitude of EPSP, and suppression of IPSP at intervals of between 50 and 500 msec peaking at 200 msec (i.e., priming effect). These changes correlated with level of IPSP_b in response to conditioned stimuli. The most pronounced effect could be seen in neurons manifesting hyperpolarizing IPSP in response to test stimuli. Suppression of test IPSP_a after superposition on IPSP_b is thought to bring about the increase in test FP and EPSP seen during priming.Institute for Brain Research, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 6, pp. 730–739, November–December, 1990.     

Suppression of associative long-term potentiation in the hippocampus after tetanization of reinforcing afferents

Field potentials (FP) induced in area C1 by gentle orthodromic stimulation were recorded in murine hippocampal slices and associative long-term potentiation (ALTP) produced by C2 tetanization associated with intensive tetanization of another group of fibers (C1) was investigated. A comparison was made between the effects of additional C1 tetanization produced at 50–300 msec before and after combined tetanization of both afferents. Where these intervals measured 50–200 msec, preliminary tetanization of C1 suppressed ALTP (rise in FP amplitude: 10.4±5.2%) in comparison with the regimen whereby additional C1 tetanization came later (giving a rise of 32.4±5.3%); no significant difference was noted at an interval of 300 msec. The three possible reasons for ALTP suppression are discussed, namely: inactivation of "fast" calcium channels, post-activation hyperpolarization of postsynaptic neurons, and synaptic inhibition. The ALTP suppression mechanism is thought to resemble that underlying the relative inefficacy of "reversible" combinations in the shaping of behavioral conditioned reflexes.Institute for Brain Research, Academy of Medical Sciences of the USSR, Moscow. Institute of Chemical Physics, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 5, pp. 636–643, September–October, 1989.     

Origin of the long positive potential in the cat superior cervical ganglion

The sucrose gap technique was used to study the long positive potential (P-potential) in a curarized cat superior cervical ganglion. The frequency of stimulating the preganglionic trunk optimal for P-potential production was 30–40 impulses/sec at a stimulus series duration of 1 sec. Proserine in low concentrations (1–5 µg/ml) increased amplitude and especially duration of the P-potential. Atropine (0.5–2 µg/ml) blocked it completely. Adrenaline and noradrenaline (10–50 µg/ml inhibited both the negative potential (corresponding to the fast EPSP of neurons) and the P-potential in equal measure. The nature of dependence of P-potential amplitude on value of the membrane potential was also studied. It was found that the P-potential is inhibited in solutions with low potassium ion content, and that amplitude of the P-potential rises with an increase of intracellular sodium concentration. The rate of its increase rises with an increase of temperature. Under the influence of strophathin, the P-potential is inhibited. The data obtained support the hypothesis that the P-potential is determined by synaptic activation of the electrogenic sodium pump.A. A. Bogomol'ets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 76–83, January–February, 1971.     

Inhibition in hippocampal pyramidal neurons during peripheral stimulation

Responses of hippocampal pyramidal neurons were investigated intracellularly in unanesthetized rabbits immobilized with tubocurarine. A single stimulus, applied to the sciatic nerve, evoked prolonged (up to 2.5 sec) hyperpolarization of the cell membrane, accompanied by inhibition of action potentials. The latent period of the evoked hyperpolarization was 48±16.4 msec, and its amplitude 2.5±1.9 mV. In some neurons the development of hyperpolarization potentials was preceded by excitation. The suggestion is made that hyperpolarization of the membrane of pyramidal cells during peripheral stimulation is manifested as an inhibitory postsynaptic potential (IPSP), generated with the participation of hippocampal interneurons. The possibility of prolonged tonic action of interneurons from outside as a cause of prolonged inhibition of the pyramidal neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 278–284, November–December, 1969.     

Mechanism of inhibition following reflex discharge in spinal cord interneurons

Using the method of microelectrode (intracellular and extracellular) recording, the mechanism of inhibition following reflex discharge in interneurons of the lumbosacral section of the spinal cord of cats on activation of cutaneous and high-threshold muscle afferents was studied. It was shown that the postdischarge depression of the reflex responses 10–20 msec after the moment of activation of the neuron is due to afterprocesses in the same neuron and presynaptic pathways. The depression of spike potentials from the 20th to the 100th msec is produced by inhibitory postsynaptic potentials (IPSP). During the development of IPSP the inhibition of spike potentials can be due to both a decrease of the depolarization of the postsynaptic membrane below the critical threshold and a decrease of sensitivity of the cell membrane to the depolarizing action of the excitatory postsynaptic potential (EPSP). At intervals between the stimuli of 30–100 msec the duration of EPSP after the first stimulus does not differ from that after the second stimulus. Hence, it is suggested that the presynaptic mechanisms do not play an essential part in this type of inhibition of interneurons. The inhibition following the excitation favors the formation of a discrete message to the neurons of higher orders.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 3–9, January–February, 1970.     

Effect of local surface cooling of the rat cortex on the impulse activity of neurons assumed to be the sources of corticofugal influences

In an experiment on albino rats with electrodermal stimulation of the forepaw evoked potentials (EP) in the neostriatum (NS), the cortical primary response (PR), and impulse reactions of neurons (mainly of layers V and VI of the cortex) were recorded. The zone of leading-off of the potentials in the cortex was subjected to local surface cooling, which led to an increase in the PR amplitude. This facilitation was accompanied by a change in the time parameters of the impulse reactions of the cortical neurons: the latency and duration increased, and a rhythmic organization of activity appeared or intensified (if it was already present). The increase in the PR amplitude and number of spikes in the response of the cortical neurons to stimulus presentation was far less intensive than the sharp increase in EP amplitude in the NS, and did not correspond to it fully in time. The data suggest that the activating influence of the corticofugal signal on EP in the NS is determined not so much by the intensity of the descending signal as by its temporal organization.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 23, No. 2, pp. 181–189, March–April, 1991.     

Excitatory postsynaptic potentials of hippocampal neurons and their extinction during repeated stimulation

A method of detecting "minimal" excitatory postsynaptic potentials (EPSP) in neurons of hippocampal area CA₃ of the unanesthetized rabbit during stimulation of the septo-fimbrial region and the dentate fascia is described. The method consists of presenting a strong (a current of up to 1 mA) conditioning stimulus, inducing a distinct inhibitory postsynaptic potential (IPSP), before a near-threshold (current of 0.03–0.35 mA) testing stimulus. The response to the testing stimulus, develoing after the previous conditioning IPSP, in most cases was purely depolarizing and, judging from the change in the latent period in some cases and the absence of correlation between its amplitude and that of the IPSP, it is a pure EPSP. If the testing stimuli are presented at low enough frequency (intervals of not less than 1 sec) the amplitude of the EPSP evoked by them gradually falls. This decrease exhibits some of the characteristic properties of extinction of behavioral responses (recovery after an interruption, a more rapid decrease during repeated series of stimuli, a slower decrease in amplitude during less frequent stimulation). The amplitude of the IPSP also fell or showed no significant change. The results are evidence in support of the hypothesis that extinction is based on a mechanism of homosynaptic depression.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 10, No. 1, pp. 3–12, January–February, 1978.     

Dynamics of cortical unit responses during defensive conditioning to sound

Several phases were distinguished in single-unit responses in areas 3 and 4 during defensive conditioning to acoustic stimulation: an initial response, short inhibition of the spike discharge, early and late after-discharges, and changes arising after the end of acoustic stimulation. The initial spike response appeared or intensified (if present already) in the first period of defensive conditioning parallel with an increase in spontaneous unit activity. After-discharges appeared later. The conditioned-reflex movement usually began 100–400 msec after stimulation began. This latent period of the first movement was the same whether for a real conditioned reflex or an after-discharge. Comparison of the latent periods of conditioned movements with the phases of the unit responses showed that the conditioned responses of the cortical neuron were primarily modified after-discharges of neurons evoked by a conditioned stimulus. Differential unit responses to acoustic stimulation, also based on after-discharges, were formed just as actively as positive. The basic role of reinforcement during conditioning is not to increase the excitability of the neurons, which is important in connection with their acquisition of polysensory properties, but to modify the after-discharges of the neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 4, pp. 339–347, July–August, 1978.     

Mechanism of the "enhancing" response in the rabbit visual cortex

Mechanisms of the "enhancing" evoked potential arising in the visual cortex in response to repeated stimulation at intervals of 100–150 msec were investigated on unanesthetized rabbits. Such intervals correspond to the phase of postinhibitory activation caused by the first (conditioning) stimulus. It is shown that the enhancing response lasts slightly longer than the primary response to a single stimulus and develops upon stimulation of the optic nerve and subcortical white substance under the point of derivation. The enhancing response is accompanied by a high-amplitude excitatory postsynaptic potential in cortical neurons and by a burst of impulse activity. Hence it can be concluded that it is generated by excitatory synapses of cortical neurons. Characteristic features of the enhancing response are the relation between the duration of the response and its amplitude (the response is shorter, the higher its amplitude) and the weak effect of the intensity of the stimulus on the amplitude of the response. An analysis of the possible mechanisms of enhancement of the response when the stimulus evoking it coincides with the phase of postinhibitory activation leads to the suggestion that this response is generated by a recurrent excitatory intracortical system. This suggestion makes it possible to explain the ability of the response to be enhanced in the presence of postinhibitory activity and some other properties of it.A. N. Severtsov Institute of Evolutionary Animal Morphology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 64–72, January–February, 1970.     

Ultrasound-induced changes in synaptic processes with different transmitters in smooth muscles

The effect of therapeutic-intensity ultrasound on neuromuscular transmission and spontaneous electrical and contractile activity in smooth muscles of the gastrointestinal tract of guinea pig was studied by a modified sucrose-gap technique. The action of ultrasound was found to facilitate the acetylcholinergic neuromuscular transmission (mainly by increasing the amplitude of excitatory postsynaptic potentials). The higher efficiency of the nonadrenergic neuromuscular transmission was manifested as an increase (nearly twofold) in the total duration, but not in the amplitude, of inhibitory postsynaptic potentials. Modulations of the first and second components of the potentials caused respectively by the action of ATP and of nitric oxide as possible transmitters, were different. Concurrently with enhancing the synaptic transmission efficiency, ultrasound exerted an opposite, inhibitory, effect on generation of spontaneous action potentials and contraction of smooth muscles. All the ultrasound effects were fully reversible. The findings permit assuming a special mechanism of modification of the synaptic transmission in smooth muscles under the action of ultrasound.Neirofiziologiya/Neurophysiology, Vol. 25, No. 4, pp. 297–302, July–August, 1993.