After-effects of repetitive stimulation in spinal neurons

Spontaneous activity of interneurons before and after repetitive stimulation at 0.1–0.5/sec was recorded in acute experiments on spinal cats and kittens. Using the dynamic selective correlation method a search was made for areas of spontaneous activity with the same distribution of action potentials in time as in the averaged evoked response to a single stimulus. In the case of some neurons portions of the background which correlate reliably in structure with the evoked response repeated at an interval equal to or a multiple of the interval of stimulation. Reproduction of the rhythm of stimulation in the spontaneous activity is intensified with an increase in the total duration of preceding stimulation with the same input and shows positive correlation with the degree of posttetanic potentiation. The facts obtained are evidence of prolonged after-processes in spinal neurons.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 272–280, May–June, 1973.     

Investigation of heterosynaptic interactions in hippocampal areas CA1, and CA3 in vitro

Heterosynaptic interactions between synapses located at a considerable distance from the cell body (perforant path) and lying close to the body of the neuron (synapses of Schaffer's collaterals and axons of the dentate fascia) on guinea pig hippocampal neurons were investigatedin vitro. It was shown by the paired stimulus method that, using stimulation of subthreshold intensity for action potential generation, spatiotemporal summation takes place in both pairs of synaptic systems. If above-threshold stimulation was used, afferents lying close to the cell body suppressed responses evoked by stimulation of distant afferents for a longer time (up to 20 msec in area CA₁ and up to 300 msec in area CA₃) than during the opposite combination of stimuli (up to 3–8 msec). After tetanization of the dentate fascia depression of responses of area CA₃ neurons to stimulation of the perforant path was observed for 2–30 min. In the remaining cases, no significant prolonged heterosynaptic posttetanic changes were observed. The possible mechanisms of these interactions are discussed.Institute of Biophysics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 524–532, November–December, 1979.     

Effect of noradrenalin and serotonin on responses of area CA3 neurons evoked in guinea pig hippocampal slices by electrical stimulation of mossy fibers

The effect of noradrenalin (NA) and serotonin (5-HT) on responses of area CA₃ cells evoked by electrical stimulation of mossy fibers was studied in slices of guinea pig hippocampus survivingin vitro. Both substances, which modify the general level and organization of spontaneous activity, also affected responses of area CA₃ cells. Changes in magnitude and structure of the response usually correlated with corresponding changes in spontaneous activity. In certain cases NA, which lowered the frequency of spontaneous activity but increased its relative content of "complex discharges" and also the number of reduced action potentials in the complex discharge, also led to an increase in the response to stimulation. 5-HT evoked periodic grouped activity in some cells and led to the appearance of such grouped discharges for the first time in the responses of other cells. Unlike NA, 5-HT caused prolonged (up to 40 min) after-facilitation of the response and an increase in spontaneous discharge frequency.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 14, No. 4, pp. 410–417, July–August, 1982.     

Frequency potentiation of synaptic response in medial bulbar tegmental neurons to microstimulation of the pontine inhibitory site

Synaptic response to single (2 Hz) and regular (30–50 Hz) stimuli applied to the pontine inhibitory site were recorded in decerebrate cats. A change to regular stimulation was usually accompanied by a rise in the firing index of synaptic discharges and raised amplitude of inhibitory and (to a lesser extent) excitatory postsynaptic potentials. Suppression of background spike activity was observed in some neurons. It was deduced that frequency potentiation makes a considerable contribution to the functional effect of stimulating the inhibitory site, i.e., terminating evoked locomotion.Institute for Information Transmission Studies, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 172–180, March–April, 1988.     

Quantitative histochemical study of monoamine oxidase in the rabbit hippocampus

The distribution of monoamine oxidase activity in the rabbit hippocampus was studied by quantitative histochemical analysis. The presence of monoamine oxidase activity was found in str. lacunosum-moleculare of areas CA₁ and CA₂ of the hippocampus and in str. moleculare of the dentate fascia. A strong positive reaction was found in layers containing many myelinated fibers (the alveus and Shaffer's collaterals). However, when the reaction was carried out without substrate, considerable deposition of diformazan was observed in these layers. These observations and the ability of myelin to reduce nitro-BT spontaneously, described in the literature, suggest that the positive Glenner's reaction in the alveus and Shaffer's collaterals is not specific. The deposition of diformazan in the layer of pyramidal and granular neurons likewise is nonspecific, as is confirmed by the results of experiments with preincubation in iproniazid and with incubation without substrate.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 9, No. 2, pp. 135–141, March–April, 1977.     

Functional development of hippocampal mossy fiber synapses in rabbits

The course of functional maturation with age of mossy fiber synapses on pyramidal cells in areas CA_3,4 of the dorsal hippocampus was investigated by extracellular recording of focal potentials and single unit responses of the hippocampus to electrical stimulation of the dentate fascia in waking, unimmobilized rabbits aged from 1 to 14 days. After the 4th day of postnatal life focal potentials appeared in response to single stimulation, in the form of a biphasic short-latency wave, characteristic of responses of the mature hippocampus, accompanied by spike discharges with a latent period of 3 to 10 msec and inhibitory responses of the hippocampal neurons. During the next 10 days the amplitude of the focal potentials increased from several hundred millivolts, with the sharpest increase observed from the 4th through the 7th days. In early age periods global and unitary responses were shown to be capable of frequency potentiation and also of short-term after-potentiation.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 12, No. 3, pp. 246–254, May–June, 1980.     

Synaptic plasticity at archicortical and neocortical levels

Research carried out by the author and his collaborators, devoted to analysis of the properties and neurophysiological mechanisms of long-term (for several hours) potentiation, is surveyed. Long-term potentiation of focal potentials and unitary responses of strictly hippocampal structures (areas CA₁ and CA₃) in the unanesthetized rabbit is described. Enhancement of excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials was found after tetanization. No corresponding changes of sensitivity to acetylcholine or acetylcholinesterase activity were found by microiontophoretic and histochemical methods during long-term potentiation. Statistical analysis of EPSPs evoked by microstimulation, based on the quantal hypothesis of synaptic transmission, showed an increase in the number of quanta of transmitter release during potentiation. Long-term potentiation of focal potentials during stimulation of the subcortical white matter in surviving neocortical slices and also long-term potentiation of focal and unitary responses of the sensomotor cortex of the unanesthetized rabbit are described. Potentiation of the "indirect" component of the global response of the pyramidal tract was found. The data suggest the presence of long-term potentiation of monosynaptic neocortical responses. It is concluded that the main mechanism of both hippocampal and neocortical long-term potentiation is increased efficiency of excitatory synapses. It is postulated that synapses modified in this way are used in the formation of memory traces.Brain Institute, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 5, pp. 651–665, September–October, 1984.     

Frequency potentiation in the neonatal rabbit hippocampus

The formation of properties of frequency potentiation in the entorhinal afferent pathway of the hippocampus was studied in unanesthetized rabbits aged from 1 to 15 days. In areas CA₁ and CA₃ of the dorsal hippocampus in newborn rabbits repetitive (1–20 Hz) electrical stimulation of the perforant path led to an increase in amplitude of the slow wave of the field potential by 20–100% compared with the control and to an increase in the probability of response discharges from the neurons from 0–0.5 in the control to 0.8–1.0 during tetanization. In rabbits aged 2–3 days potentiation was more marked at a frequency of 4–6 Hz, whereas depression of the responses developed rapidly to a higher frequency of stimulation. The frequency optimum of 4–15 Hz was established on the 5th day. Potentiation of the first component of the field potential was observed starting from the 8th–10th day of life. The experimental results show that the property of frequency potentiation in the cortical afferent connections of the hippocampus is found in rabbits actually at birth, and it acquires the adult form at the beginning of the second week of life.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 533–539, November–December, 1979.     

Functional characteristics of Schaffer's collaterals studied in vivo and in vitro

A comparative analysis was made of the functional characteristics of connections between hippocampal areas CA₃ and CA₁ (Schaffer's collaterals) in experiments in vivo on unanesthetized rabbits and in vitro on surviving slices of guinea pig hippocampus, with extracellular recording in area CA₁. In the case of electrical stimulation of the collaterals in vitro, post-activational inhibition was weak, responses of inhibition of spontaneous discharges were absent, and low frequencies of stimulation were more effective than in vivo. Posttetanic changes were found more frequently in experiments in vitro and they lasted longer than in vivo. The predominant effect of tetanization under normal conditions was depression, but during incubation it was facilitation of responses. The possible causes of these differences are discussed.Institute of Biophysics, Academy of Sciences of the USSR, Puschino-on-Oka. Translated from Neirofiziologiya, Vol. 11, No. 3, pp. 208–217, May–June, 1979.     

Short- and long-term potentiation in afferent pathways of the neonatal rabbit hippocampus

Vocal potentials were recorded in hippocampal area CA₁ and dentate fascia in unanesthetized rabbits aged from 1 to 50 days during stimulation of Schaffer's collaterals and the perforant path, respectively, with paired (interval 15–100 msec) and repetitive (20–40 Hz for 3–5 sec) electric pulses. Short-term potentiation of focal potentials during paired stimulation and post-tetanic potentiation lasting from a few minutes to 3 h were shown to be reproduced in the hippocampus from the first days after birth, whereas in the dentate fascia, which matures later, reproduction began on the 8th–10th day, when neurons first began to respond to stimulation of the corresponding afferent pathways.     

Spatial distribution of hippocampal response to tooth pulp stimulation and acoustic stimulation

Evoked potentials (EP) and neuronal responses produced by tooth pulp stimulation and a clicking sound were recorded at different hippocampal sites using microelectrodes in unrestrained rats. Spatial distribution of EP was found to be the same for both types of stimulation. Averaged EP consisted of a high amplitude negative preceded by a low-amplitude positive component (N₁ and P₁, respectively). Latency of the N₁ wave reached its minimum (of 27 msec) at the middle third of the molecular layer of the dentate gyrus and the outer portion of the CA₃ apical dendrites. Latency of N₁ was considerably longer in the stratum radiatum layer of the CA₁. Laminar profiles of the amplitude of the N₁ componenent of EP produced in the dentate gyrus and the CA₃ by tooth pulp stimulation resemble those observed during perforant path stimulation; in the CA₁ they are similar to those evoked by stimulating the Schaffer collaterals. Maximum amplitude of the P₁ component was observed above the pyramidal layer of the CA₁ and the hilus. Neuronal discharge pattern changed in all hippocampal regions under the effects of both tooth pulp stimulation and the clicking sound. It is deduced that information can reach the hippocampus by two routes: via a "fast" (inhibitory) pathway through the fimbria and the fornix and a slower (excitatory) path through the entorhinal cortex.P. Flexig Institute for Brain Research, Karl Marx University, Leipzig, DR. Institute of Physiology, Pecs University Medical School, Pecs, Hungary. Translated from Neirofiziologiya, Vol. 19, No. 1, pp. 36–46, January–February, 1987.     

Synaptic transmission in slices of rat hippocampus using a modified voltage clamp technique

A small modification to a voltage-clamp set-up for studying isolated neurons, and the use of simple hippocampal slices allowed stable recording of excitatory postsynaptic currents (EPSCs) that were evoked by stimulating the Shaffer's collaterals of individual CA1 pyramidal neurons. With the developed method EPSCs and focal extracellular potentials could be recorded simultaneously. It was confirmed that the EPSC consists of two components that are mediated via N-methyl-D-aspartate (NMDA)- and non-NMDA-receptors. The effects of different blockers of these receptors on the postsynaptic current were investigated, as were the effects of adenosine, which, depending on its concentration, could either depress or potentiate the synaptic transmission.A. A. Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 731–738, November–December, 1991.     

Two patterns of bulbar neuronal response to microstimulation of locomotor and inhibitory brain stem sites

Synaptic responses (postsynaptic potentials and action potentials) were evoked in mesencephalic decerebellated cats by stimulating pontine bulbar locomotor and inhibitory sites (LS and IS, respectively) with a current of not more than 20 µA in "medial" and "lateral" neurons of the medulla. Some neurons even produced a response to presentation of single (actually low — 2–5 Hz — frequency) stimuli. The remaining cells responded to stimulation at a steady rate of 30–60 Hz only. Both groups of medial neurons were more receptive to input from LS. Lateral neurons responding to even single stimuli reacted more commonly to input from LS and those responding to steady stimulation only to input from IS. Many neurons with background activity (whether lateral or medial) produced no stimulus-bound response, but rhythmic stimulation either intensified or inhibited such activity. This response occurs most commonly with LS stimulation. Partial redistribution of target neurons in step with increasing rate of presynaptic input may play a major part in control of motor activity.Institute for Research into Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 257–266, March–April, 1990.     

Post-tetanic strengthening of evoked electrical responses of the sensomotor cortex]

A study has been made of the posttetanic potentiation of evoked potentials (PTP EP) in the sensorimotor cortex, appearing in response to VPL stimulation. A distinct PTP EP of the cortical surface has been found as well as considerable differences in its intensity recorded at different portions of deep cortical layers (700 to 1600 mu). Suggestions were made regarding the origin of the phenomena observed.     

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.     

Effect of electrical stimulation of the septum on subicular neurons with different kinds of spontaneous activity in rabbits

The effect of electrical stimulation of the medial nucleus of the septum and of hippocampal area CA₁ on subicular neurons with three different types of spontaneous activity (with theta-modulation, with delta-modulation and complex spikes, and with irregular single-spike activity) was studied in unanesthetized rabbits by extracellular recording of unit activity. Cells with theta-activity were found to respond in a distinctive functional manner to stimulation of the medial nucleus of the septum: Their reactivity was higher but latent periods of their responses were much shorter than those of cells with delta-activity and irregular discharges. Stability of modulation of theta-cell activity increased both during and after stimulation of the medial septal nucleus. Electrical stimulation of hippocampal area CA₁, on the other hand, led to disappearance of rhythm modulation. Average response latencies of all three types of cells to stimulation of area CA₁ were equal. The results indicate special properties of the septal input to subicular cells with theta-modulation.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 326–333, May–June, 1985.     

Prolonged posttetanic changes in the sensorimotor cortex of the waking rabbit in response to stimulation of the fibers of the substantia alba in the neocortex and corpus callosum]

Study of posttetanic changes in the sensorimotor cortex of the alert rabbit in response to stimulation of callosal fibres of the white matter have shown that in comparison to the control level either a prolonged increase (potentiation) of the tested evoked potentials to the stimulation of the same structures takes place, or the amplitude of the tested evoked potentials decreases (depression). Both processes can take place simultaneously in different layers of the cortex.     

Effects of vasopressin and oxytocin on evoked dorsal horn cell activity in an isolated segment of spinal cord

During experiments on an isolated segment of the spinal cord of 2- to 3-week-old rats, a study was made of the effects of vasopressin and oxytocin on the activity of dorsal horn cells produced by stimulating the afferent root. Both field and action potentials were recorded in single cells. It was established that vasopressin and oxytocin produced reversible inhibition of the postsynaptic component of field potentials. The amplitude of potentials was reduced by 33–39% by vasopressin and by 12–34% using oxytocin. The effect of the test substances depended on the concentration used and the duration of their action on the brain. Both vasopressin and oxytocin reversibly depressed discharges of single dorsal horn cells evoked by stimulating the dorsal root. These two neuropeptides prolonged latency, and reduced the number of evoked potentials or completely suppressed response. A facilitatory effect was recorded in a small number of cells. We deduced from our findings that their hypothalamospinal neurohormonal system inhibits transmission of afferent impulses at the level of interneurons of the dorsal horn.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 634–640, September–October, 1985.     

Comparison of direct influences of the perforant path on hippocampal CA1 and CA3 neurons in vitro

The efficiency of synapses of the perforant path located on terminals of apical dendrites of CA₁ and CA₃ neurons was investigated in sections of the guinea pig hippocampus in vitro. Neurons of both areas were shown to respond to stimulation of the perforant path by action potential generation. Responses of most CA₁ neurons appeared to repetitive stimulation with a frequency of up to 30–80/sec. Neurons in area CA₃ respond only to low-frequency stimulation (under 5/sec). Posttetanic potentiation of responses to stimulation of the perforant path was found in both areas of the hippocampus.Institute of Biophysics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 303–310, July–August, 1979.     

Double evoked responses to the electrical stimulation of Shaffer's collaterals in CA1 hippocampal field

Double evoked responses to single current pulses applied to Shaffer's collaterals were observed in CAI hippocampal field in freely moving rats. The second response was an irregular population EPSP with constant latency sometimes accompanied by a population spike. The effect was observed in 22 of 54 tested rats (40.74%). In 10 of these 22 animals (45.45%) the second response was evoked by a weak testing stimulus of at least of a single collateral, in the remaining 12 rats the second response appeared to stimulation with increased current or after potentiation of the stimulated pathways. The second responses were very sensitive to the functional state of an animal and were recorded at the state of rest or during sleep. The latencies of the second response measured from the beginning of the first response were very close in different animals and with low intraindividual variability indicating that the same circuits are involved in its generation. It is suggested that hippocampus can support dynamic processes such as reverberation of signals.