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Results for “Inhibitory Postsynaptic Potentials”

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PubMed1996

Synaptic interactions between primate precentral cortex neurons revealed by spike-triggered averaging of intracellular membrane potentials in vivo.

To document synaptic interactions between neurons in the precentral cortex of macaque monkeys, we recorded in vivo the intracellular (IC) membrane potentials of cortical neurons simultaneously with extracellular (EC) action potentials of neighboring cells. The synaptic potentials correlated with EC spikes were obtained by spike-triggered averages (STA) of the IC membrane potentials for 373 cell pairs recorded in anesthetized and awake behaving monkeys. Sixty-three STAs (17%) showed excitatory postsynaptic potentials (EPSPs), beginning after the trigger spike. Pure EPSPs had onset latencies of 0.9 +/- 0.7 msec (mean +/- SD) and amplitudes of 226 +/- 130 microV. Sixteen STAs (4%) showed postspike inhibitory postsynaptic potentials (IPSPs), with onset latencies of 0.4 +/- 0.4 msec and amplitudes of -274 +/- 188 microV. The most common waveform, observed in 82% of the STAs with features, was a broad depolarization straddling the trigger spikes, reflecting synchronized synaptic input to both IC and EC neurons. These average synchronous excitation potentials (ASEPs) began 14.3 +/- 6.6 msec before the trigger spike and had amplitudes of 1064 +/- 867 microV. Twenty-three STAs (6%) showed an average synchronous inhibitory potential (ASIP): a hyperpolarization beginning before the trigger spike and reflecting IPSPs produced by a group of local inhibitory cells synchronized with the trigger cell. ASIPs had an onset latency of -5.5 +/- 2.7 msec and amplitude of -589 +/- 502 microV. Combinations of synchronous and postspike potentials were also observed. Successive recordings provided examples of convergent and divergent connections between EC and IC cells. Neuron pairs with depolarizing postsynaptic potentials (PSPs) in the STA yielded peaks in the cross-correlograms of the IC and EC action potentials; the peak area was proportional to the amplitude of the PSP. These data suggest that a significantly larger proportion of cortical neurons interact through synchronous activity than through simple serial interactions; moreover, synchronous excitation affected more widely separated cell pairs than EPSPs and IPSPs, which were seen most often among the closest cells.

Action Potentials↗

PubMed1988

Intracellular injection of apamin reduces a slow potassium current mediating afterhyperpolarizations and IPSPs in neocortical neurons of cats.

Electrophysiologic effects of intracellularly injected apamin, a Ca2+-dependent K+ channel blocker, were investigated in neurons of the motor cortex of awake cats. Single-electrode voltage clamp techniques were used to measure changes in membrane currents including those that were synaptically activated. All changes occurred within 2-4 min after pressure injection of apamin with partial recovery observed within 8-15 min. Apamin selectively abolished an outward current that mediated a slow afterhyperpolarization (AHP) following intracellular depolarizing current pulses and action potentials without influencing the time course of the action potentials or an associated fast AHP component. In addition apamin increased the number and frequency of spike discharges evoked by the depolarizing current pulses and produced a small increase in the rate of background firing activity. The baseline resting potential and input resistance were essentially unchanged by apamin. Apamin also diminished a late, slowly decaying component of inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) elicited by stimulation of the ventrolateral thalamus or the pyramidal tract. The apamin-induced changes were concomitant with a decrease of the decay time constant of both IPSPs and IPSCs and a positive shift in their reversal potential. The results suggest that the late, slowly decaying component of these inhibitory postsynaptic responses is generated by an apamin-sensitive Ca2+-dependent K+ conductance which is also responsible for the slow AHP.

Action Potentials↗

PubMed1996

GABA-induced responses in electrophysiologically characterized neurons within the rat rostro-ventrolateral medulla in vitro.

Rostro-ventrolateral medulla (RVL) neurons were recorded using conventional intracellular recording techniques in brain slices maintained in vitro at 32 degrees C and classified into 3 major groups. The first group included neurons having endogenous pacemaker-like (PL) activity with regular firing frequency (mean 8 Hz) and a linear current-voltage relationship (I-V). The second group of neurons were slowly and irregularly firing (IF) or quiescent, presenting membrane potential oscillations and their I-V usually displayed an inward rectification. These neurons had a relatively longer action potential duration. The third group included silent neurons (S) with no apparent membrane oscillations and they differed from the first two groups by having relatively shorter action potential duration and amplitude and lower cell input resistance. When recorded with KCl-filled electrodes, the majority of silent neurons displayed a time-dependent inward rectification. With KAc-filled electrodes, irregular slow hyperpolarizing and depolarizing spontaneous potentials could be recorded primarily on PL and IF neurons, respectively. Moreover, fast spontaneous inhibitory postsynaptic potentials (PSPs) were detected in about 15% of PL and S neurons. They generally exhibited a regular pattern and were depolarizing when KCl-filled electrodes were used for recording. The amplitude of these inhibitory PSPS was reversibly reduced by the GABA A antagonists bicuculline, SR 95531 and picrotoxin. With KAc-filled electrodes, pressure-applied GABA (20 mM) evoked complex responses. In PL neurons, it consisted of a fast hyperpolarization followed by a slower depolarization that were both sensitive to SR 95531 and picrotoxin. The response was terminated by a long-lasting hyperpolarization that was reduced, but not abolished, by the GABA B antagonist CGP 35348. In IF and S neurons, GABA application usually produced a fast followed by a slow monophasic hyperpolarization and depolarization, respectively. The fast component of these responses was sensitive to the GABA A antagonists. Pressure application of isoguvacine (10 mM) always induced monophasic responses in all types of neurons recorded. Baclofen (1-30 mu M) reduced the firing frequency and hyperpolarized PL and IF neurons, an effect that was antagonized by CGP 35348 (50-100 mu M); however, it had little effect on silent neurons. It is concluded that RVL neurons have heterogeneous electrophysiological characteristics. Their predominant synaptic input and GABA responsiveness might be additional criteria to identify the excitatory and inhibitory elements in the RVL circuitry. All neuronal types seem to have functional GABA A and GABA B receptors; however, only a subpopulation is under tonic inhibitory control in vitro, probably from local GABAergic pacemaker interneurons. Our results further emphasize the role of GABA as an important neurotransmitter in the RVL network.

Animals↗

PubMed1995

Outward chloride/potassium co-transport in insect neurosecretory cells (DUM neurones).

The mechanism underlying outward chloride transport in the cell body and in the neuritic field of cockroach Dorsal Unpaired Median (DUM) neurones was assessed using the intracellular microelectrode technique. The chloride equilibrium potential was indirectly estimated from the reversal potentials of responses to gamma-aminobutyric acid (GABA) pressure ejections and of inhibitory postsynaptic potential (IPSP) evoked by electrical stimulation of the anterior connectives. Changes in intracellular chloride concentration [Cl-]i following various treatments were estimated from the amplitude changes of soma GABA responses and IPSP. Decreasing external Cl- concentration reduced the amplitude of GABA-mediated inhibitory events without affecting the membrane potential. Cl-/K+ co-transport was assessed by increasing external K+ concentration. The rate of outward Cl- movement was reduced furosemide but not by SITS or DIDS. All these results suggest that Cl- is not passively distributed in DUM neurones and that an active outwardly directed Cl-/K+ co-transport is implicated in the regulation of [Cl-]i.

Animals↗

PubMed1975

Inhibitory and excitatory effects of CNS depressants on invertebrate synapses.

(1) The effects of pentobarbital were studied on the membrane properties and synaptic activity of crustacean neuromuscular junction preparations and molluscan neurons. (2) Pentobarbital selectivity depressed in a dose-dependent, reversible manner the exciatory postynaptic potentials (EPSPs) recorded at crustacean neuromuscular junctions without altering either inhibitory postsynaptic potentials (IPSPs) or post-synaptic membrane properties. (3) Pentobarbital depressed cholinergic EPSPs recorded in an identified molluscan neuron and depressed the depolarizing phase of biphasic PSP without affecting the hyperpolarizing phase of the BPSP on the same cell. Facilitation of the EPSP was not affected. (4) Pentobarbital did not appreciably alter the reversal potentials of the EPSP and IPSP. (5) Low concentrations of pentobarbital did not alter the appearance of spontaneously occurring IPSPs, while high concentrations changed the pattern of regular IPSP input to an irregular, burst-like pattern. (6) Pentobarbital and 5 other CNS depressants (cholralose, chloroform, ethanol, and urethane) increased the excitability and altered the current--voltage relations of a cell whose membrane properties have been proposed as a model of presynaptic terminal membranes. The effects were dependent on the species of external divalent cation present. (7) The results in these invertebrate systems may provide insight into the cellular basis of the depressant and excitatory effects of these agents.

Acetylcholine↗

PubMed1981

Sucrose-gap recordings of nerve-evoked potentials in mammalian parasympathetic ganglia.

The sucrose-gap recording technique was used to study mammalian parasympathetic ganglionic transmission. Both a fast nicotinic depolarization potential and a slow muscarinic hyperpolarizing potential were recorded in vesical pelvic ganglia (VPG). A long afterhyperpolarization caused by an electrical response of through-fibers was also recorded. However, a slow excitatory postsynaptic potential (S-EPSP) was not readily observed and may be masked by the long afterhyperpolarization. In addition, the slow inhibitory postsynaptic potential (S-IPSP) of the VPG was due to a direct effect of acetylcholine (ACh). Thus, sucrose-gap recordings of VPG potentials are similar to those obtained in sympathetic ganglia, but the mechanism for transmission of the S-IPSP may be different in the respective ganglia.

Acetylcholine↗

PubMed1989

Tongue-muscle-controlling motoneurons in the Japanese toad: neural inputs from the thalamus.

The anuran tongue is an effector organ specialized for snapping up prey during visually guided prey-catching behavior. As a step toward elucidating the control mechanisms of the tongue movement and overall organization of visually guided behavior, properties of neural inputs from the thalamus (of which electrical stimulation elicited a behavior very similar to the visually guided predator-avoidance behavior under freely behaving conditions) were investigated in paralyzed Japanese toads. Tongue-muscle-controlling motoneurons (tongue-protractor motoneurons (PMNs) and tongue-retractor motoneurons (RMNs)) were identified antidromically, and synaptic inputs in response to electrical stimuli applied to various points in the thalamus (mainly the posterocentral thalamic nucleus) were examined. Hyperpolarizing potentials were evoked in both PMNs and RMNs in response to single electrical stimuli applied to the thalamus contralateral or ipsilateral to the recording side. Since these potentials reversed to depolarizing ones after injecting Cl- ions into the cell interior, these hyperpolarizing potentials were concluded to be the usual fast type of inhibitory postsynaptic potentials (IPSPs). On the other hand, depolarizing potentials which were superimposed on the underlying IPSPs were evoked when repetitive electrical stimuli were applied to the thalamus. The amplitude of these depolarizing potentials was decreased when depolarizing currents were injected intracellularly, while it was increased when hyperpolarizing currents were injected, indicating that these depolarizing potentials are excitatory postsynaptic potentials (EPSPs).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1992

Voltage-dependent 40-Hz oscillations in rat reticular thalamic neurons in vivo.

Extra- and intracellular recordings of thalamic reticular and relay neurons were performed in rats under urethane anaesthesia. Under this type of anaesthesia it was found that, throughout the whole reticular thalamic nucleus, a large proportion of cells (approximately 34%) discharged like clocks within a 25-60 Hz frequency band width (i.e. 40 Hz). Simultaneous recordings of pairs of reticular cells showed that the regular discharges of nearby units were not synchronous. Thus, the asynchronous 40-Hz firing of reticular thalamic cells was not correlated with any 40-Hz extracellular activity as revealed by the spectral analysis of the electroencephalogram and by recordings performed in various thalamic nuclei. In relay cells of the ventrobasal, ventral lateral and posterior thalamic nuclei, the regular firing of reticular thalamic neurons induced a rhythmic inhibitory modulation that was detected by the time-series analysis of the inhibitory postsynaptic potentials. In many relay cells, however, the disclosure of this inhibitory modulation required cellular depolarization since the resting potential in these cells was maintained at the reversal potential of the inhibitory events. Intracellular recordings of reticular thalamic cells showed that their regular firing was not driven in an all-or-nothing manner by 40-Hz synaptic inputs but rather that it depended upon the activation of a voltage-dependent pacemaker mechanism; this pacemaker activity was manifested by the presence of subthreshold oscillations that drove spike discharges and whose frequency was voltage dependent. In the context of data already published on the genesis of 40-Hz oscillations in the brain, and given the key position of reticular thalamic neurons in thalamocortical networks, the present results indicate that the reticular thalamic nucleus might play a pacemaker function in the genesis of 40-Hz oscillations in the thalamus and cortex during states of focused arousal.

Animals↗

PubMed1999

Two electrophysiologically distinct types of granule cells in epileptic human hippocampus.

We investigated the electrophysiology of morphologically identified human granule cells with conventional current-clamp recordings. Slices were prepared from 14 human epileptic sclerotic hippocampi. Granule cells appeared to have a diverse electrophysiology. Each cell was distinguished by the shape of the afterhyperpolarization following single action potentials. Two types could be discerned: type I afterhyperpolarizations were monophasic and brief (typically 10-40 ms), whilst type II afterhyperpolarizations were biphasic and long (typically 50-100 ms). The two types also differed in their repetitive firing behaviour and action potential morphology: type I cells had significantly weaker spike frequency adaptation, lower action potential amplitude and smaller action potential upstroke/downstroke ratio. Thus, the firing pattern of type I cells resembled that of rodent dentate interneurons. In contrast, the corresponding parameters of type II cells were comparable to rodent dentate granule cells. Despite the distinct firing patterns, membrane properties were not different. The two types of cells also differed in their synaptic responses to stimulation of the perforant path. At strong suprathreshold stimulation intensity, type I cells always generated multiple action potentials, whereas type II cells usually spiked once only. Slow inhibitory postsynaptic potentials were not detected in type I neurons, but were easily identified in type II neurons. Extracellular recordings of perforant path-evoked field potentials in the cell layer confirmed that the majority of granule cells showed multiple discharges even when we recorded simultaneously from a type II cell that generated one action potential only. The morphology of both types of cells was characteristic of what has been described for primate dentate granule cells. Based on comparisons with previous studies on rodent and human granule cells, we tentatively hypothesize that: (i) the majority of granule cells from sclerotic hippocampus display an hyperexcitable epileptogenic electrophysiology; (ii) there is a subset of granule cells whose electrophysiology is preserved and is more comparable to granule cells from non-epileptic hippocampus.

Adult↗

PubMed2001

Neuronal bursting induced by NK3 receptor activation in the neonatal rat spinal cord in vitro.

Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period +/- SD was 2.8 +/- 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5-20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 +/- 2 s (average interburst interval 55 +/- 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-D-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3 receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.

Animals↗

PubMed1992

Correlates of Habituation of a Polysynaptic Reflex in Crayfish In Vivo and In Vitro.

Reflex leg levation habituates during repeated electrical stimulation of mechanosensory afferents in the dactyl of the fifth walking leg of the crayfish, Procambarus clarkii. This was investigated in decerebrate crayfish, and reproduced in an isolated thoracic ganglion preparation. In vivo, trains of stimuli delivered every 2.5 s produced a gradual decrease in the amplitude of the mechanical response, and a concomitant decrease in the number of impulses per burst in the levator muscle myogram. Near complete recovery occurred after 10 min rest, and transient dishabituation was observed after electrical stimulation of the telson. Less frequent or stronger stimuli led to less rapid habituation. In vitro, the same parametric characteristics of habituation were observed in the levator nerve responses, while the intrinsic variability of the reflex was reduced. The response decrement was shown to be unrelated to changes in the afferent excitation. Evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in levator motorneurons decreased in parallel with the levator neurogram. This decrease was unrelated to any change in the resting membrane potential of the levator motorneurons. Interneurons with habituating EPSPs, antagonistic depressor motorneurons with habituating inhibitory postsynaptic potentials and non-habituating responses in other motorneuronal groups were also found. These findings point to a central locus of habituation upstream from the motorneurons, and offer prospects for a detailed investigation of the mechanisms of habituation in a polysynaptic system.

Journal Article↗

PubMed2001

Differential changes of synaptic transmission in spiny neurons of rat neostriatum following transient forebrain ischemia.

Spiny neurons in neostriatum are vulnerable to cerebral ischemia. To reveal the mechanisms underlying the postischemic neuronal damage, the spontaneous activities, evoked postsynaptic potentials and membrane properties of spiny neurons in rat neostriatum were compared before and after transient forebrain ischemia using intracellular recording and staining techniques in vivo. In control animals the membrane properties of spiny neurons were about the same between the left and right neostriatum but the inhibitory synaptic transmission was stronger in the left striatum. After severe ischemia, the spontaneous firing and membrane potential fluctuation of spiny neurons dramatically reduced. The cortically evoked initial excitatory postsynaptic potentials were suppressed after ischemia indicated by the increase of stimulus threshold and the rise time of these components. The paired-pulse facilitation test indicated that such suppression might involve presynaptic mechanisms. The inhibitory postsynaptic potentials in spiny neurons were completely abolished after ischemia and never returned to the control levels. A late depolarizing postsynaptic potential that was elicited from approximately 5% of the control neurons by cortical stimulation could be evoked from approximately 30% of the neurons in the left striatum and approximately 50% in the right striatum after ischemia. The late depolarizing postsynaptic potential could not be induced after acute thalamic transection. The intrinsic excitability of spiny neurons was suppressed after ischemia evidenced by the significant increase of spike threshold and rheobase as well as the decrease of repetitive firing rate following ischemia. The membrane input resistance and time constant increased within 6 h following ischemia and the amplitude of fast afterhyperpolarization significantly increased after ischemia. These results indicate the depression of excitatory monosynaptic transmission, inhibitory synaptic transmission and excitability of spiny neurons after transient forebrain ischemia whereas the excitatory polysynaptic transmission in neostriatum was potentiated. The facilitation of excitatory polysynaptic transmission is stronger in the right neostriatum than in the left neostriatum after ischemia. The suppression of inhibitory component and the facilitation of excitatory polysynaptic transmission may contribute to the pathogenesis of neuronal injury in neostriatum after transient cerebral ischemia.

Action Potentials↗

PubMed1993

A comparison of rat hippocampal mossy cells and CA3c pyramidal cells.

1. There is a long-standing debate about whether the large spiny cells in the hilar region of the hippocampus should be classified as pyramidal cells of Ammon's horn or as a distinct cell type of the dentate gyrus. The rationale for grouping these hilar neurons (termed "mossy cells") with pyramidal cells of Ammon's horn is shared characteristics. In the present study we have compared the morphological and physiological characteristics of mossy cells and nearby CA3c pyramidal cells with the use of a rat hippocampal slice preparation. 2. Biocytin-labeled neurons were examined on the basis of soma area, location, shape, number of primary dendrites, extent of dendritic spines, dendritic location, and axon trajectories. Mossy cells had larger soma areas than CA3c pyramidal cells, and they had more large complex spines (thorny excrescences) on their proximal dendrites and somata than CA3c pyramidal cells. Mossy cell dendritic trees and axon collaterals ramified in different regions of the hippocampus than dendrites and axons of CA3c pyramidal cells. 3. Intrinsic physiological properties, and spontaneous and evoked synaptic properties, were measured and compared. Mossy cells had significantly higher input resistances, smaller amplitude burst afterhyperpolarizations, smaller amplitude action potentials, less spike-frequency adaptation, and more anomalous rectification than CA3c pyramidal cells. 4. Mossy cells had spontaneous excitatory postsynaptic potentials (EPSPs) that were significantly higher in frequency and larger in amplitude than CA3c pyramidal cells. A larger proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with depolarizing postsynaptic potentials without any apparent hyperpolarization. Conversely, a smaller proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with inhibitory postsynaptic potentials (IPSPs), and spontaneous IPSPs were more difficult to detect in mossy cells. 5. The intrinsic physiological properties of mossy cells endow these cells with potent excitatory mechanisms but relatively fewer inhibitory control processes than CA3c pyramidal cells. Recordings of spontaneous and evoked PSPs suggest that mossy cells receive more excitatory input and less inhibitory input than CA3c pyramidal cells. These intrinsic and synaptic properties of mossy cells may explain this cell type's exceptional vulnerability to excitotoxic damage by intense afferent stimulation. 6. In summary, mossy cells were significantly different from CA3c pyramidal cells in many of their morphological, intrinsic physiological, and synaptic properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed2001

The motor inhibitory system operating during active sleep is tonically suppressed by GABAergic mechanisms during other states.

The present study was undertaken to explore the neuronal mechanisms responsible for muscle atonia that occurs after the microinjection of bicuculline into the nucleus pontis oralis (NPO). Specifically, we wished to test the hypothesis that motoneurons are postsynaptically inhibited after the microinjection of bicuculline into the NPO and determine whether the inhibitory mechanisms are the same as those that are utilized during naturally occurring active (rapid eye movement) sleep. Accordingly, intracellular records were obtained from lumbar motoneurons in cats anesthetized with alpha-chloralose before and during bicuculline-induced motor inhibition. The microinjection of bicuculline into the NPO resulted in a sustained reduction in the amplitude of the spinal cord Ia-monosynaptic reflex. In addition, lumbar motoneurons exhibited significant changes in their electrophysiological properties [i.e., a decrease in input resistance and membrane time constant, a reduction in the amplitude of the action potential's afterhyperpolarization (AHP) and an increase in rheobase]. Discrete, large-amplitude inhibitory postsynaptic potentials (IPSPs) were also observed in high-gain recordings from lumbar motoneurons. These potentials were comparable to those that are only present during the state of naturally occurring active sleep. Furthermore, stimulation of the medullary nucleus reticularis gigantocellularis evoked a large-amplitude IPSP in lumbar motoneurons after, but never prior to, the injection of bicuculline; this reflects the pattern of motor responses that occur in conjunction with the phenomenon of "reticular response-reversal." The preceding changes in the electrophysiological properties of motoneurons, as well as the development of active sleep-specific IPSPs, indicate that lumbar motoneurons are postsynaptically inhibited following the intrapontine administration of bicuculline in a manner that is comparable to that which occurs spontaneously during the atonia of active sleep. The present results support the conclusion that the brain stem-spinal cord inhibitory system, which is responsible for motor inhibition during active sleep, can be activated by the injection of bicuculline into the NPO. These data suggest that the active sleep-dependent motor inhibitory system is under constant GABAergic inhibitory control, which is centered in the NPO. Thus during wakefulness and quiet sleep, the glycinergically mediated postsynaptic inhibition of motoneurons is prevented from occurring due to GABAergic mechanisms.

Animals↗

PubMed1976

Potentiation of dopaminergic transmission by phosphodiesterase inhibitors and cyclic nucleotides.

Experiments were made to determine whether cyclic AMP plays a role in transmission at identified dopaminergic synapses in the water snail Planorbis corneus. Intracellular stimulation of a specific dopamine neuron produces direct inhibitory postsynaptic potentials (ipsps) in a number of other neurons. These ipsps, which are mediated by dopamine, were potentiated by as much as 120% by caffeine, theophylline or dibutyryl cyclic AMP, although they were unaffected by cyclic AMP and prostaglandin E1. Caffeine and theophylline also potentiated the inhibitory response to dopamine, applied to the postsynaptic neurons by perfusion or iontophoresis, but the effects were generally much smaller (maximum potentiation 30%). The results provide evidence that postsynaptic cyclic AMP is involved in transmission at these synapses, but that the phosphodiesterase inhibitors may also have a presynaptic effect.

Action Potentials↗

PubMed2003

GABAB receptor- and metabotropic glutamate receptor-dependent cooperative long-term potentiation of rat hippocampal GABAA synaptic transmission.

Repetitive stimulation of Schaffer collaterals induces activity-dependent changes in the strength of polysynaptic inhibitory postsynaptic potentials (IPSPs) in hippocampal CA1 pyramidal neurons that are dependent on stimulation parameters. In the present study, we investigated the effects of two stimulation patterns, theta-burst stimulation (TBS) and 100 Hz tetani, on pharmacologically isolated monosynaptic GABAergic responses in adult CA1 pyramidal cells. Tetanization with 100 Hz trains transiently depressed both early and late IPSPs, whereas TBS induced long-term potentiation (LTP) of early IPSPs that lasted at least 30 min. Mechanisms mediating this TBS-induced potentiation were examined using whole-cell recordings. The paired-pulse ratio of monosynaptic inhibitory postsynaptic currents (IPSCs) was not affected during LTP, suggesting that presynaptic changes in GABA release are not involved in the potentiation. Bath application of the GABAB receptor antagonist CGP55845 or the group I/II metabotropic glutamate receptor antagonist E4-CPG inhibited IPSC potentiation. Preventing postsynaptic G-protein activation or Ca2+ rise by postsynaptic injection of GDP-beta-S or BAPTA, respectively, abolished LTP, indicating a G-protein- and Ca2+-dependent induction in this LTP. Finally during paired-recordings, activation of individual interneurons by intracellular TBS elicited solely short-term increases in average unitary IPSCs in pyramidal cells. These results indicate that a stimulation paradigm mimicking the endogenous theta rhythm activates cooperative postsynaptic mechanisms dependent on GABABR, mGluR, G-proteins and intracellular Ca2+, which lead to a sustained potentiation of GABAA synaptic transmission in pyramidal cells. GABAergic synapses may therefore contribute to functional synaptic plasticity in adult hippocampus.

Animals↗

PubMed2007

Developmental differences in neuromodulation and synaptic properties in the lamprey spinal cord.

Functional properties in the spinal cord change during development to adapt motor outputs to differing behavioral requirements. Here, we have examined whether there are also developmental differences in spinal cord plasticity by comparing the neuromodulatory effects of substance P in the larval lamprey spinal cord with its previously characterized effects in premigratory adults. The premigratory adult effects of substance P were all significantly reduced in larvae. As the adult effects of substance P depend on the N-methyl-d-aspartate (NMDA)-dependent potentiation of glutamatergic synaptic transmission, we examined if the developmental differences in neuromodulation were associated with differences in synaptic properties. We found that the amplitude, rise time, and half-width of excitatory postsynaptic potentials (EPSPs) from excitatory network interneurons were all significantly reduced in larvae compared with adults. These differences were associated with a reduction in the NMDA component of larval EPSPs, an effect that could have contributed to the reduced modulatory effects of substance P in larvae. In contrast to glutamatergic inputs, the amplitude, rise time, and half-width of inhibitory postsynaptic potentials (IPSPs) from ipsilateral inhibitory interneurons were all significantly increased in larvae compared with adults. Substance P also potentiated larval IPSP amplitudes, an effect not seen in adults. This increase in inhibition contributed to the reduced effects of substance P in larvae, as premigratory adult-like modulation could be evoked when inhibition was blocked with strychnine. These results suggest that opposite developmental changes in excitatory and inhibitory synaptic transmission and their modulation are associated with developmental differences in spinal cord neuromodulation.

Age Factors↗

PubMed1978

Vestibulo-ocular reflex from the posterior canal nerve to extraocular motoneurons in the cat.

In the anesthetized cat, the posterior canal nerve (PCN) was stimulated by electric pulses and synaptic responses were recorded intracellularly in the three antagonistic pairs of extraocular motoneurons. Pure reciprocal effects were obtained in the motoneurons innervating the antagonistic pair of ipsilateral oblique muscles and the antagonistic pair of contralateral vertical rectus muscles. These responses consisted of low threshold disynaptic excitatory postsynaptic potentials (EPSPs) in either the contralateral superior oblique (c--SO) (trochlear) or contralateral inferior rectus (c--IR) motoneurons and of disynaptic inhibitory postsynaptic potentials (IPSPs) in either the ipsilateral inferior oblique (i--IO) or ipsilateral superior rectus (i--SR) motoneurons. In addition, disynaptic IPSPs were also found in (i--SO) motoneurons. Mixtures of low threshold (di or trisynaptic) EPSPs and IPSPs were found in all other extraocular motoneurons except for the contralateral lateral rectus (c--LR) motoneurons. These results may afford a basis for the characteristic eye movements induced by vertical canal nerve stimulation.

Animals↗