A depolarizing inhibitory postsynaptic potential activated by synaptically released gamma-aminobutyric acid under physiological conditions in rat hippocampal pyramidal cells

We report that CA1 pyramidal neurons of the rat hippocampus respond to high intensity afferent stimulation by generating a late depolarizing potential that typically occurs between the early (fast) inhibitory postsynaptic potential (IPSP) and the late (slow) IPSP. This potential is reminiscent of the response seen after the application of 4-aminopyridine and can be blocked by bicuculline, indicating that GABAA receptors are involved in its generation.     

Hyperpolarizing potentials in guinea pig hippocampal CA3 neurons

There is a bewildering variety of hyperpolarizing potentials which control activity in hippocampal pyramidal cells. These include an inhibitory postsynaptic potential (IPSP) with early and late components, voltage- and calcium-dependent potassium conductances, a voltage-dependent potassium conductance modulated by muscarinic agents (the M-current), and a complex and poorly understood afterhyperpolarization following epileptiform bursts. In hippocampal CA3 pyramidal cells, mossy fiber stimulation elicits an IPSP which is made up of two readily separable components. Using the in vitro slice preparation, we investigated the underlying ionic basis of these IPSP components and compared them to other hyperpolarizing potentials characteristic of the CA3 neurons. Intracellular recordings were obtained and then tissue was exposed to bathing medium low in chloride concentration or high in potassium concentration; the ion "blockers" EGTA (intracellular); tetraethylammonium (TEA) (intra- and extracellular), and barium and cobalt (extracellular); and the gamma-aminobutyric acid (GABA)/chloride antagonists penicillin, bicuculline and picrotoxin.     

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.     

Corticofugal postsynaptic influences on red nucleus neurons

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

Corticofugal influences on reticulospinal neurons of the gigantocellular nucleus in cats

It was shown by intracellular recording that stimulation of the motor cortex evokes E PS Ps and I PS Ps in reticulospinal neurons of the gigantocellular nucleus of the cat medulla. The E PS Ps appeared in 94.3% and the I PS Ps in 5.7% of neurons tested. Analysis of the presynaptic pathway showed that 77.4% of E PS Ps studied arose through monosynaptic, and 22.6% through polysynaptic corticoreticular connections. By their latent period, duration, and rise time up to a maximum the monosynaptic E PS Ps were divided into two groups: "fast" and "slow." It is postulated that "fast" E PS Ps are generated in reticulospinal neurons which are activated by fast-conducting fibers and "slow" E PS Ps by slowly conducting corticobulbar fibers. I PS Ps were recorded from reticulospinal neurons that also were inhibited by stimulation of the ventral columns of the spinal cord. The hypothesis is put forward that cortical motor signals in cats can be transmitted to the spinal cord via monosynaptic and polysynaptic connections of "fast" and "slow" pyramidal neurons with reticulospinal neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 3, pp. 250–257, May–June, 1976.     

Action of strychine on evoked potentials and postsynaptic responses of cat sensomotor cortical neurons

Acute experiments on immobilized cats lightly anesthetized with pentobarbital showed that application of strychine to the cortical surface inhibits slow negative potentials arising during direct and primary responses of the sensomotor cortex and corresponding IPSPs in pyramidal neurons. Iontophoretic applications of strychine blocks predominantly the early component of the IPSP, during which the input resistance under normal conditions is significantly less than during the late component of the IPSP, indicating that these components differ in their genesis. It is concluded that individual components of cortical evoked potentials have a common genesis, and that the slow negative potential is the dipole reflection of the IPSP in pyramidal neurons; the early component of the IPSP, moreover, is generated as a result of activation of axo-somatic inhibitory synapses, whereas the late component is generated as a result of activation of axo-dendritic synapses. The mediators in these inhibitory synapses may be different.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 16, No. 4, pp. 480–487, July–August, 1984.     

Responses of bulbar neurons to stimulation of locomotor and inhibitory sites in the cat brainstem

Bulbar locomotor and inhibitory sites were located in the pons of mesencephalic decerebellate cats. Rhythmic stimulation of locomotor sites through microelectrodes at the rate of 60 Hz elicited stepping movements in the forelimbs which were halted when the inhibitory sites were rhythmically stimulated. Neuronal response was elicited by single or paired stimulation of locomotor sites at the rate of 1.5 Hz or by applying a series of 2–4 stimuli spaced 2 msec apart to the inhibitory site. Medial neurons generated synaptic responses (postsynaptic potentials or action potentials) to stimulation of the inhibitory site twice as frequently as when the locomotor site was stimulated. Responses in lateral neurons, however, occurred twice as frequently to stimulation of the locomotor site, while IPSP were only observed half as often as EPSP in neurons of both groups. In neurons excited by stimulation of the locomotor site, stimulation of the inhibitory site did not normally produce IPSP. Possible mechanisms underlying the halt of locomotion occurring in response to stimulation of the inhibitory site are discussed.Information Transmission Institute, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 525–533, July–August, 1986.     

Neurochemical and ionic mechanisms of dorsal root potentials in the spinal cord of immature rats

Dorsal root potentials (DRPs) were recorded by a sucrose gap method in experiments on parasagittal slices of the isolated rat spinal cord. In most cases the DRP consisted of fast and slow waves. The fast wave of DRP was inhibited by the GABA antagonist picrotoxin and the blocker of GABA-activated chloride channels, furosemide, but it was potentiated by pentobarbital sodium. The slow wave of DRP disappeared if the extracellular K⁺ concentration was raised to 10 mM and it was depressed by tetraethylammonium and 4-aminopyridine, blockers of electrically excitable potassium channels. It is concluded that the fast wave of DRP and the initial components of the slow wave of DRP are GABA-ergic in origin; the slow wave of DRP, however, is linked with an increase in extracellular K⁺ concentration near the primary afferent terminals. The possible mechanisms of the increase in extracellular K⁺ concentration during dorsal root stimulation are discussed.A. M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 16, No. 6, pp. 796–800, November–December, 1984.     

Involvement of calcium-dependent potassium conductance in membrane hyperpolarization processes at the pyramidal cell membrane in the cat sensorimotor cortex

In acute experiments on cats immobilized with myorelaxants intracellular injection of Cs ions reduced IPSP amplitude and postburst hyperpolarization of pyramidal cells in the sensorimotor cortex. Intracellular injection of ethylene glycol tetra-acetic acid produced a similar effect. The latter substance barely altered the lead front of neuronal after-hyperpolarization arising after a single action potential, while the lag front was inhibited. In conclusion, calcium-dependent potassium conductance may play an important part in the genesis of IPSP and of post-burst and after-hyperpolarization at the membrane of pyramidal cells of the cat sensorimotor cortex.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 3, pp. 383–389, May–June, 1988.     

Gaba sensitivity of the somata and dendrites of pyramidal cells in isolated slices of rat hippocampus

During experiments on isolated slices slices of rat hippocampus the inhibitory action of -aminobutyric acid (GABA) was investigated on the excitation of field CA, pyramidal neurons, together with the effects of bicuculline, penicillin and thiopentone on this process. It was found that GABA effectively and reversibly reduced the amplitude of the antrodomic population spike in the area of both the somata and the dendrites of these cells. The sensitivity of apical dendrites to GABA exceeded that of the somata by one order, increasing in a proximal-distal direction. The somata of pyramidal neurons were marked by pronounced desensitization to GABA. Bicuculline and penicillin acted as GABA antagonists at all the levels of CA, pyramidal cells investigated. Bicuculline blocked the effects of GABA on somata and dendrites in almost equal measure. The antagonistic effects of penicillin were 10 times greater in the pyramidal layer than in the dendritic region. Thiopentone reinforced the inhibitory effects of GABA. The potentiating effects of thiopentone were exerted most strongly on the dendrites. It is postulated that the membrane of field CA, neurons contain two types of bicuculline-sensitive GABA receptors, differing in their location (mainly on the cell body or dendrite), their pharmacology, and degree of desensitization to GABA.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 6, pp. 737–746, November–December, 1985.     

Aspects of excitation and inhibition produced in parietal association cortex neurons by stimulating thalamic association nuclei

Neuronal response to single stimuli applied to the thalamic dorsolateral and posterolateral nuclei (DLN and PLN resepctively) was investigated in the parietal association cortex. Primary IPSP following DLN and PLN stimulation was noted in 62.5% and 79.6% of instances respectively. Latencies of EPSP and IPSP when stimulating the two nuclei were longer for the DLN. The amplitude of EPSP evoked by stimulating association nuclei rose and declined smoothly, while that of IPSP showed a fast rise and a more steady decline. The EPSP appearing during the evolution of IPSP were of higher amplitude than control level of resting potential. Both amplitude and duration of IPSP induced in a single unit by stimulating different association nuclei were extremely similar, thus confirming the involvement in this operation of the same inhibitory cortical interneurons. Duration of IPSP was shorter than that of inhibitory background spike activity. It is postulated that the discrepancy in duration can largely be ascribed to properties of the neurons themselves.State University, Odessa. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 529–536, September–October, 1991.     

Short-latency unit responses of the lateral geniculate body to electrical stimulation of the optic tract in rats

Short-latency responses of single relay neurons of the lateral geniculate body to electrical stimulation of the optic tract were studied. The response of many neurons was complex and could consist of a series of (1–3) spikes with fixed latent periods. Each spike of such a response can be recorded on the EPSP in the absence of other spikes, preserving its latent period. The fixed latent periods of different relay neurons may vary from one to another. In the intervals between spikes with these latent periods active inhibition (IPSP) takes place. The series of spikes, EPSP, and IPSP is completed, as a rule, by a long IPSP.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 5, No. 1, pp. 28–32, January–February, 1973.     

Copper sensitivity in dorsal hippocampus slices

The action of copper on the pyramidal neurons in CA1 of the hippocampus is little understood. Our main aim was to study the possible interaction of copper on the synaptic network in CA1 pyramidal neurons. We used Wistar rats hippocampus slices in a recording chamber. The population response ("population of spikes") collected by an extracellular micropipette under baseline conditions served as control. Copper, GABA, bicuculline and picrotoxin were delivered in different experimental conditions to the slice. One, 10 and 100 microM of copper concentration decreased significantly the amplitude and duration of the population spikes in relation to the control response. This effect did not show concentration dependency. Copper in bicuculline medium decreased significantly the duration response in relation to the control response and in relation to copper effect in a free bicuculline medium. This phenomenon emphasizes the copper action on the GABA (B) and (C) receptors. Copper in a picrotoxin medium increased significantly the excitability of the response. This new effect suggests that copper acts on non-GABA receptors, an effect that could be detected when the GABA receptors were inactivated. As a result of these findings it appears that, under our experimental conditions, copper generated transient sensitivity changes in pyramidal neurons of CA1 dorsal hippocampus.     

Effects of intracellular injection of chloride ions on inhibitory postsynaptic potentials and postburst hyperpolarization in cat sensorimotor cortex neurons

It was shown during acute experiments on cats immobilized with myorelaxants that intracellular injection of chloride ions into both pyramidal and non-pyramidal neurons of the sensorimotor cortex produces the early component only of IPSP, while the late phase and postburst hyperpolarization of pyramidal neurons are not very sensitive to this effect. It is deduced that membrane permeability to chloride ions increases during the early component of IPSP in pyramidal and nonpyramidal neurons of the cat sensorimotor cortex, while the late phase and postburst hyperpolarization is less dependent on chloride permeability.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 453–460, July–August, 1986.     

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.     

Dendritic action potentials of pyramidal tract neurons in the cat sensorimotor cortex

The intracellular activity of pyramidal tract neurons was studied during electrical stimulation of ventrolateral and ventroposterolateral thalamic nuclei in acute experiments on cats immobilized by myorelaxants. Somatic action potentials were observed and spontaneous spikes were also produced by single and rhythmic stimulation of the thalamic nuclei at the rate of 8–14 Hz, by iontophoretic application of strychnine, and by intracellular depolarizing current pulses. These potentials had a relatively low and variable amplitude of 5–60 mV and are presumed to be dendritic action potentials. It is postulated that these variable potentials arise in the dendrites of pyramidal neurons with multiple zones generating such activity. No interaction was observed where somatic and dendritic action potentials occur simultaneously. The possible functional role of dendritic action potentials is discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 435–443, July–August, 1986.     

Subunit Composition and Function of GABAA Receptors of Rat Spermatozoa

GABA triggers mammalian sperm acrosome reaction (AR). Here, evidence is presented, showing that rat spermatozoa contain GABA_A receptors, composed of ₅, ₁ and ₃ subunits. The effects of GABA_A receptor agonist and antagonist on the induction of AR in rat spermatozoa were assessed using the chlortetracycline assay. Muscimol, a GABA_A receptor agonist, triggered AR; whereas bicuculline, a GABA_A receptor antagonist and picrotoxin, a GABA_A receptor/Cl^– channel blocker, inhibited the ability of GABA or progesterone to induce AR. In conclusion, GABA_A receptors appear to mediate the action of progesterone in inducing AR in rat spermatozoa.     

Synaptic nature of the principal components of the evoked potential in the general cortex of the turtle forebrain

The nature of the principal components of the evoked potential of the general cortex of the turtle forebrain was studied in response to electrical stimulation of the contralateral optic nerve. Comparison of these components with postsynaptic potentials of the neurons of this structure showed that the four fast negative waves of the evoked potential correspond to fast EPSPs, which are independent of one another. The positive wave of the evoked potential is the sum of several IPSPs. The slow negative and, to some extent, the positive wave are a reflection of the slow EPSP. It is shown that early EPSPs are generated on portions of the apical dendrites which are further from the soma than those generating late fast EPSPs and also the IPSP and slow EPSP. Axo-somatic contacts are perhaps also concerned in the generation of the last-named potential.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 5, No.3, pp.261–271, May–June, 1973.     

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.     

Glial origin of the slow negative potential of the direct cortical response: Microelectrode study and mathematical analysis

The slow negative potential of the direct cortical response is similar in its shape, time course, and relationship to repetitive stimulation to depolarization of cortical glial cells but differs from the IPSP of cortical neurons. According to the results of digital spectral (frequency) analysis, the basis of the slow negative potential is the glial component formed by summation of components which coincide with glial depolarization processes with an accuracy determined by a constant factor. The much smaller component (as regards relative contribution) is the indirect result of the development of an IPSP in the neurons.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 14, No. 1, pp. 76–84, January–February, 1982.