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PubMed1987

Behavioral state-specific inhibitory postsynaptic potentials impinge on cat lumbar motoneurons during active sleep.

High-gain intracellular records were obtained from lumbar motoneurons in intact, undrugged cats during naturally occurring states of wakefulness, quiet sleep, and active sleep. Spontaneous, discrete, inhibitory postsynaptic potentials (IPSPs) were found to impinge on lumbar motoneurons during all states of sleep and wakefulness. IPSPs which occurred during wakefulness and quiet sleep were of relatively low amplitude and had a low frequency of occurrence. During the state of active sleep there occurred a great increase in inhibitory input. This was the result of the appearance of large-amplitude IPSPs and of an increase in the frequency of low-amplitude IPSPs which were indistinguishable from those recorded during wakefulness and quiet sleep. In addition to a difference in amplitude, the time course of the large IPSPs recorded during active sleep further differentiated them from the smaller IPSPs recorded during wakefulness, quiet sleep, and active sleep; i.e., their rise-time and half-width were of longer duration and their rate-of-rise was significantly faster. We suggest that the large, active sleep-specific IPSPs reflect the activity of a group of inhibitory interneurons which are inactive during wakefulness and quiet sleep and which discharge during active sleep. These as yet unidentified interneurons would then serve as the last link in the brain stem-spinal cord inhibitory system which is responsible for producing muscle atonia during the state of active sleep.

Action Potentials↗

PubMed1987

Valproate enhances inhibitory postsynaptic potentials in hippocampal neurons in vitro.

Effects of sodium valproate (0.5-10 mM) on hippocampal cells (CA3 pyramidal cells and granule cells) of the guinea pig in vitro were studied by intra- and extracellular recording. Inhibitory postsynaptic potentials were markedly and reversibly augmented. Their shunting action as well as duration increased by more than 150%. Effects of locally administered gamma-aminobutyric acid (GABA) did not change significantly. Membrane characteristics such as membrane potential, membrane input resistance and action potential did not alter. Valproate suppressed spontaneous spiking and repetitive discharges evoked by GABA antagonists. It is concluded that valproate enhances GABAergic synaptic transmission by a presynaptic mechanism. However, postsynaptic mechanisms might be involved in the limitation of repetitive firing.

Animals↗

PubMed1998

Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons.

Rapid information transfer within the brain depends on chemical signalling between neurons that is mediated primarily by glutamate and GABA (gamma-aminobutyric acid), acting at ionotropic receptors to cause excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs), respectively. In addition, synaptically released glutamate acts on metabotropic receptors to excite neurons on a slower timescale through second-messenger cascades, including phosphoinositide hydrolysisl. We now report a unique IPSP mediated by the activation of metabotropic glutamate receptors. In ventral midbrain dopamine neurons, activation of metabotropic glutamate receptors (mGluR1) mobilized calcium from caffeine/ryanodine-sensitive stores and increased an apamin-sensitive potassium conductance. The underlying potassium conductance and dependence on calcium stores set this IPSP apart from the slow IPSPs described so far. The mGluR-induced hyperpolarization was dependent on brief exposure to agonist, because prolonged application of exogenous agonist desensitized the hyperpolarization and caused the more commonly reported depolarization. The rapid rise and brief duration of synaptically released glutamate in the extracellular space can therefore mediate a rapid excitation through activation of ionotropic receptors, followed by inhibition through the mGluR1 receptor. Thus the idea that glutamate is solely an excitatory neurotransmitter must be replaced with a more complex view of its dual function in synaptic transmission.

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PubMed1990

Serotonin-mediated inhibitory postsynaptic potential in guinea-pig prepositus hypoglossi and feedback inhibition by serotonin.

1. Intracellular recordings were made from neurones of the nucleus prepositus hypoglossi (PH) in slices of guinea-pig brain. Focal stimulation evoked an inhibitory postsynaptic potential (IPSP) that was typically 10-25 mV in amplitude and 1 s in duration. The IPSP reversal potential showed a Nernstian dependence on the external potassium concentration ([K+]o). 2. Spiperone blocked the IPSP with an IC50 of 40 nM, while ketanserin and (-)sulpiride had no effect. Cocaine (1 microM) prolonged the IPSP half-duration by 157%, and increased the amplitude by 28%. 3. 5-Hydroxytryptamine (5-HT, serotonin) hyperpolarized PH cells with an EC50 of 8.5 microM in control, and 135 nM in cocaine (10 microM). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) also hyperpolarized PH cells with an EC50 of 16 nM, although the maximal effect was only 81% of the maximum 5-HT hyperpolarization. Spiperone produced a parallel, right shift of the 5-HT concentration-response curve; Schild analysis gave a Kd of 10 nM. Application of 5-HT to neurones voltage-clamped near their resting potential (about -55 mV) caused an outward current and an increase in membrane conductance. 4. The amplitude of the IPSP was reversibly decreased by non-hyperpolarizing concentrations of 5-HT and by the 5-HT1 receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP). The IC50 values for the latter two compounds were 50 nM and 1.5 microM, respectively; the maximal effect was a 90% inhibition. Neither compound affected the membrane potential nor changed the hyperpolarization induced by 5-HT. Quipizine competitively antagonized TFMPP with an estimated Kd of 165 nM. 5. When trains of stimuli were applied, an inhibition of the IPSP was observed following the first stimulus. At a frequency of 1 Hz, the inhibition was approximately 75%. This frequency-dependent 'run-down' of the IPSP was markedly attenuated by pre-treatment with TFMPP (1 microM). 6. It is concluded that the IPSP in PH cells is caused by 5-HT acting on 5-HT1A receptors to activate a potassium conductance. The release of 5-HT can be inhibited by activation of a presynaptic 5-HT1D receptor. This presynaptic receptor appears to be at least partly responsible for the run-down phenomenon, and may be involved in the physiological regulation of 5-HT synaptic transmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1985

Excitatory and inhibitory postsynaptic potentials in alpha-motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region.

We tested the hypothesis that stimulation of the mesencephalic locomotor region (MLR) activates polysynaptic pathways that project to lumbar spinal motoneurons and are involved in the initiation of locomotion. Fictive locomotion was produced by MLR stimulation, and intracellular records of evoked postsynaptic potentials (PSPs) in alpha-motoneurons were computer analyzed. Stimulation of sites in the MLR that were maximally effective for the initiation of locomotion produced excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in all the motoneurons examined. The amplitudes of the PSPs increased as locomotion commenced. The EPSPs were largest during the depolarized phase of the step cycle, and in 17 of our 22 cells the EPSP was replaced by an IPSP of slightly longer latency during the hyperpolarized phase. The mean latency of the EPSPs measured from the stimulus artifact produced by stimulation of the MLR was 5.1 ms (3.0-7.0 ms). In all cases, the IPSP occurred 0.6 ms or more after the onset of the EPSP in the same cell. Later PSPs were sometimes observed as well. The effects of constant current injection on the membrane potential oscillations associated with fictive locomotion (locomotor drive potentials) were examined. The results showed that the amplitudes of the locomotor drive potentials (LDPs) could be affected by depolarizing and hyperpolarizing current injection. The data is consistent with the LDP having a predominant inhibitory component, which is more readily altered by current injection than is the excitatory component. The effect of constant current injections on the MLR-evoked PSPs was also examined, and it was observed that both EPSPs and IPSPs could be affected by the injected currents. The EPSPs increased in amplitude with constant hyperpolarizing current injection, and this fact rules out the possibility that the EPSP is actually a reversed IPSP. The IPSP was decreased in amplitude by hyperpolarizing current injection. Combined stimulation of the MLR and the ipsilateral high-threshold muscle or cutaneous afferents produced facilitation of both short- and long-latency MLR-evoked PSPs, suggesting that the two pathways share common interneurons. The possibility that the long-latency PSPs are produced by rapid oscillation in the locomotor central pattern generator is discussed. We concluded that MLR stimulation that evokes fictive locomotion produces both excitation and inhibition of spinal motoneurons. Spinal interneuronal systems are implicated and may be those involved in the initiation and control of locomotion. The probable relay sites for the descending pathway from the MLR to motoneurons are discussed.

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PubMed2002

Effects of methylphenidate on the inhibitory postsynaptic potential in rat locus coeruleus neurons.

Effects of methylphenidate (MPH), an agent used clinically for the treatment of children presenting the attention-deficit/hyperactivity disorder (AD/HD), on synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular recording methods. Bath-application of MPH (30 nM-3 microM) increased the amplitude of the inhibitory postsynaptic potential (IPSP), while it did not change the amplitude of the excitatory postsynaptic potential (EPSP). MPH increased the time-to-peak and the half-decay time of the IPSP in LC neurons. MPH increased the amplitude of spontaneous IPSP: individual spontaneous IPSPs merged one into the other so as to produce regular, long-lasting waves of hyperpolarization. Clonidine (10 nM), a selective agonist for alpha 2-adrenoceptors, depressed the IPSP without affecting the EPSP in LC neurons. The results suggest that MPH enhances inhibitory synaptic transmission in the rat LC by depressing the norepinephrine (NE) re-uptake system.

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PubMed1992

GABAB receptor-mediated inhibitory postsynaptic potentials evoked by electrical stimulation and by glutamate stimulation of interneurons in stratum lacunosum-moleculare in hippocampal CA1 pyramidal cells in vitro.

Following micropressure application of glutamate (500 microM) in stratum lacunosum-moleculare (L-M), inhibitory postsynaptic potentials (glut-IPSPs) were recorded in CA1 pyramidal cells. These glut-IPSPs were blocked by tetrodotoxin (1 microM) and, thus, were probably generated by the activation of local interneurons. The effects of pharmacological antagonists on glut-IPSPs and on electrically-evoked early and late IPSPs were assessed in the same cells during the same application of the antagonist. Local application of the GABAB antagonist 2-OH saclofen (1-4 mM) reduced both glut-IPSPs and late IPSPs but not early IPSPs. In contrast, the GABAB antagonist phaclofen (20 mM) reduced late IPSPs but not early IPSPs but not early IPSPs or glut-IPSPs. Early IPSPs were blocked by the GABAA antagonists bicuculline and picrotoxin but late IPSPs and glut-IPSPs were not. Repetitive electrical stimulation depressed early and late IPSPs as well as glut-IPSPs, suggesting that interneurons activated with glutamate were also stimulated electrically. Thus, interneurons in str. lacunosum-moleculare appear to inhibit pyramidal cells via a GABAB receptor-mediated IPSP. The discrepancy in the pharmacological profile of the GABAB glut-IPSPs and of the GABAB late IPSPs may suggest the presence of two GABAB mechanisms in CA1 pyramidal cells.

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PubMed1988

Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat.

1. Pyramidal neurones from layers II and III of the rat primary somatosensory cortex and cat primary visual cortex were studied in vitro. Inhibitory postsynaptic potentials (IPSPs) and responses to exogenously applied gamma-aminobutyric acid (GABA) and its analogue baclofen were characterized. The results from rats and cats were very similar. 2. Single electrical stimuli to deep cortical layers evoked a sequence of PSPs in the resting neurone: (a) an initial, brief excitation (EPSP), (b) a short-latency, fast inhibition (the f-IPSP) and (c) a long-latency, more prolonged inhibition (the l-IPSP). The f-IPSP was accompanied by a large conductance increase (about 70-90 nS) and reversed polarity at -75 mV; the l-IPSP displayed a relatively small conductance increase (about 10-20 nS) and reversed at greater than -90 mV. 3. Focal application of GABA near the soma evoked a triphasic response when measured near the threshold voltage for action potentials: (a) the GABAhf (hyperpolarizing, fast) phase was very brief and was generated by a large conductance increase with a reversal potential of -78 mV, (b) the GABAd (depolarizing) phase also had a high conductance but reversed at -51 mV, (c) the GABAhl (hyperpolarizing, long-lasting) phase had a relatively low conductance and reversed at -70 mV. The GABAhf response was specifically localized to the soma, whereas the apical or basilar dendrites generated predominantly GABAd responses. 4. Baclofen, a selective GABAB receptor agonist, caused a small (about 2 mV), slow hyperpolarization of the resting potential, which reversed at -90 mV. Saturating baclofen doses increased membrane conductance by a maximum of about 12 nS. Baclofen depressed the amplitude and conductance of PSPs; when baclofen was focally applied near the soma. IPSPs were selectively depressed. 5. The GABAA receptor antagonists bicuculline methiodide or picrotoxin (10 microM) greatly depressed f-IPSPs, but either enhanced or did not affect l-IPSPs. Concomitantly, GABAhf and GABAd responses were antagonized, leaving a more prominent GABAhl response that reversed polarity at a more negative level of -87 mV. Baclofen responses were unaffected by bicuculline and picrotoxin. Extracellular barium abolished the baclofen response, and shifted the reversal potentials of the GABAd and GABAhl responses in the positive direction; the GABAhf response was unaffected. 6. Both focal GABA and f-IPSPs strongly depressed the intrinsic excitability of pyramidal neurones. Each greatly increased spike threshold and abolished or vastly reduced the capacity of the cells to fire repetitively during intense stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1989

Inhibitory postsynaptic potentials in neonatal rat sympathetic preganglionic neurones in vitro.

1. Intracellular recordings were made from antidromically identified sympathetic preganglionic neurones (SPNs) in transverse sections of thoraco-lumbar spinal cord from neonatal (12-22 day) rats. 2. Two types of hyperpolarizing (inhibitory) postsynaptic potentials (IPSPs) were recorded in the SPNs. The first type, which we have termed unitary IPSPs, were small, discrete IPSPs that occurred spontaneously and also following chemical or electrical stimulation applied to the spinal cord slices. The second type IPSP was a hyperpolarizing response evoked by either dorsal or ventral root stimulation. 3. Spontaneously occurring unitary IPSPs had an amplitude of 1 to 5 mV, and reversal potential of -60 to -75 mV; they were reversibly abolished by low Ca2+, tetrodotoxin (TTX) or strychnine but not by bicuculline and picrotoxin. 4. Pressure application of N-methyl-D-aspartate (NMDA), an excitatory amino SPNs; these were abolished by either strychnine or by the NMDA receptor antagonist D-2-amino-5-phosphonovalerate. Furthermore, electrical stimulation of dorsal rootlets elicited in several SPNs the discharge of strychnine-sensitive unitary IPSPs. 5. Electrical stimulation applied to dorsal or ventral rootlets elicited in nineteen and eight SPNs, respectively, an IPSP of larger amplitude (5 to 15 mV). The IPSP exhibited a reversal potential of -60 to 75 mV; it was changed to a depolarizing response in a low [Cl-]o solution, but was not significantly affected in a low [K+]o. Strychnine but not bicuculline or picrotoxin reversibly blocked the IPSPs in nearly all the SPNs. Additionally, hexamethonium and d-tubocurarine antagonized the IPSPs evoked by ventral but not by dorsal root stimulations. 6. Our results suggest that unitary and evoked IPSPs recorded in SPNs are due primarily to an increase of Cl- conductance by glycine or a glycine-like substance, released from interneurones, that can be activated by NMDA. Furthermore, IPSPs evoked by ventral root stimulation appear to represent a disynaptic event whereby nicotinic activation of a glycine-releasing interneurone results in a release of the inhibitory transmitter; this is then analogous to the Renshaw cell circuitry of the spinal motoneurones.

Animals↗

PubMed1991

Inhibition in postischemic rat hippocampus: GABA receptors, GABA release, and inhibitory postsynaptic potentials.

We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p greater than 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p less than 0.01) in all hippocampal subfields 1-21 days after ischemia. Using microdialysis in CA1, we found that K(+)-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p greater than 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p greater than 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be useful in the treatment of ischemic CA1 pyramidal cell death in the rat.

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PubMed2001

Neuronal network analysis based on arrival times of active-sleep specific inhibitory postsynaptic potentials in spinal cord motoneurons of the cat.

The neuronal network responsible for motoneuron inhibition and loss of muscle tone during active (REM) sleep can be activated by the injection of the cholinergic agonist carbachol into a circumscribed region of the brainstem reticular formation. In the present report, we studied the arrival times of inhibitory postsynaptic potentials (IPSPs) observed in intracellular recordings from cat spinal cord motoneurons. These recordings were obtained during episodes of motor inhibition induced by carbachol or during motor inhibition associated with naturally occurring active sleep. When the observed IPSP arrival times were analyzed as a superposition of renewal processes occurring in a pool of pre-motor inhibitory interneurons, it was possible to estimate the following parameters: (1) the number of independent sources of the IPSPs; (2) the rate at which each source was bombarded with excitatory postsynaptic potentials (EPSPs); and (3) the number of EPSPs required to bring each source to threshold. From the data based upon the preceding parameters and the unusually large amplitudes of the active sleep-specific IPSPs, we suggest that each source is a cluster of synchronously discharging pre-motor inhibitory interneurons. The analysis of IPSP arrival times as a superposition of renewal processes, therefore, provides quantitative information regarding neuronal activity that is as far as two synapses upstream from the site of the recording electrode. Consequently, we suggest that a study of the temporal evolution of these parameters could provide a basis for dynamic analyses of this neuronal network and, in the future, for other neuronal networks as well.

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PubMed1969

Organization of inhibition in abdominal ganglion of Aplysia. II. Posttetanic potentiation, heterosynaptic depression, and increments in frequency of inhibitory postsynaptic potentials.

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Action Potentials↗

PubMed1999

Modulatory effects of adenosine on inhibitory postsynaptic potentials in the lateral amygdala of the rat.

1. Adenosine is a depressant in the central nervous system with pre- and postsynaptic effects. In the present study, intracellular recording techniques were applied to investigate the modulatory effects of adenosine on projection neurons in the lateral rat amygdala (LA), maintained as slices in vitro. 2. Adenosine reversibly reduced the amplitude of a fast inhibitory postsynaptic potential (IPSP) that was evoked by electrical stimulation of the external capsule and pharmacologically isolated by applying an N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor antagonist, DL-(-)-2-amino-5-methyl-4-isoxazolepropionic acid and 6, 7-Dinitroquinoxaline-2,3-dione, respectively, and the gamma-aminobutyric acidB (GABAB) receptor antagonist CGP 35348. The postsynaptic potential that remained was abolished by locally applying bicuculline. 3. Adenosine reduced the amplitude of the fast IPSP on average by 40.3%. It had no significant effect on responses to exogenously applied GABA, on membrane potential or on input resistance, suggesting that the site of action was at presynaptic inhibitory interneurons in the LA. 4. The response to adenosine was mimicked by the selective adenosine A1 receptor agonist N6-cyclohexyladenosine and blocked by the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. 5. Neuronal responsiveness in the amygdala is largely controlled by inhibitory processes. Adenosine can presynaptically downregulate inhibitory postsynaptic responses and could exert dampening effects likely by depression of both excitatory and inhibitory neurotransmitter release.

Adenosine↗

PubMed1990

The slow inhibitory postsynaptic potential in rat hippocampal CA1 neurones is blocked by intracellular injection of QX-314.

Intracellular recordings were made from CA1 pyramidal neurones in the rat hippocampus slice preparation. The recording electrodes contained potassium acetate (4 M) with or without the quaternary lidocaine derivative, QX-314 (50 mM). Both fast (f) and slow (s) inhibitory postsynaptic potentials (IPSP) were evoked by low-frequency orthodromic stimulation. The s-IPSP was rapidly reduced by QX-314 injection. It decreased along a similar time course to the dV/dt of the action potential (AP). The f-IPSP and excitatory postsynaptic potential were not significantly reduced in size at a time when the s-IPSP was virtually abolished by QX-314. It is concluded that conductance through the K+ channels which are coupled to GABAB receptors is readily blocked by QX-314, while the Cl- channels which are coupled to GABAA receptors and the cation channels coupled to the glutamate receptors are relatively resistant to the local anaesthetic.

Action Potentials↗

PubMed1990

Mu opioid receptor activation reduces inhibitory postsynaptic potentials in hippocampal CA3 pyramidal cells of rat and guinea pig.

Using intracellular recording techniques, we characterized synaptic responses of CA3 pyramidal cells to mu and kappa agonists in hippocampal slices from rats and guinea pigs. In rat CA3 pyramidal cells, the mu selective agonist (N-MePhe3,D-Pro4)-morphiceptin (PLO17) inhibited both the early and the late inhibitory postsynaptic potentials (IPSPs) and increased excitatory postsynaptic potential (EPSP) amplitudes. Voltage clamp analysis of synaptic currents indicated that the excitatory postsynaptic current were not increased by PLO17, showing that the apparent increase in EPSPs was a result of a decrease in the underlying IPSP. The kappa agonists trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate and dynorphin A (1-17) had no effect on EPSPs or IPSP conductances measured in rat pyramidal cells. Maximal inhibition of IPSPs by PLO17 resulted in a bursting response to stimulation in rat but not guinea pig CA3 pyramidal cells. In guinea pig CA3 pyramidal cells, PLO17 also inhibited IPSP conductances but did not affect EPSP amplitudes. In contrast to the lack of effect in rat pyramidal cells, trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate (100 nM) inhibited the late IPSP conductance without influencing the EPSP or the early IPSP conductance of guinea pig pyramidal cells. Dynorphin A (1-17) (0.01-10 microM) did not affect resting membrane properties or evoked synaptic conductances in either preparation. Mu receptor activationin the CA3 of rats and guinea pigs results in the inhibition of inhibitory synaptic input to pyramidal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1980

Single-shot channel activation accounts for duration of inhibitory postsynaptic potentials in a central neuron.

In the goldfish Mauthner cell, inhibitory postsynaptic currents evoked by intracellular stimulation of presynaptic neurons decay exponentially, with a mean time constant of 6.65 milliseconds. Analysis of membrane conductance fluctuations induced by iontophoresis of glycine and gamma-aminobutyric acid indicates a mean inhibitory channel lifetime of 7.15 milliseconds. The results thus suggest that the relaxation kinetics of activated inhibitory channels are rate-limiting during decay of the inhibitory postsynaptic current.

Animals↗

PubMed1993

Anoxic depression of excitatory and inhibitory postsynaptic potentials in rat neocortical slices.

1. The effects of brief anoxia (4-6 min replacement of O2 by N2) on synaptic potentials evoked from layer IV and/or the white matter were studied in pyramidal neurons of layers II-III from rat neocortical slices. 2. The early and late components of excitatory postsynaptic potentials (EPSPs) showed differential sensitivity to anoxia: within 2 min the late EPSP (lEPSP) disappeared, whereas the amplitude of the early EPSP (eEPSP) decreased by 70% at 5 min of anoxia. Recovery was complete within 4-11 min. 3. Both fast and slow inhibitory postsynaptic potentials (IPSPs) were extremely sensitive to lack of O2 and were abolished earlier than the lEPSP evoked by the same stimulus. As well, recovery of the IPSPs was always more delayed than that of the EPSPs. 4. A transient increase in excitability during early anoxia and/or midrecovery, manifested as enhanced probability of spiking in 25% of neurons, is attributed to the higher sensitivity of IPSPs compared with EPSPs. 5. The anoxic-induced depression of the lEPSP and IPSPs, which are generated close to the soma, is not due to depolarization-induced occlusion; however, occlusion may cause an attenuation of the eEPSP at dendritic sites. 6. The depression of the EPSPs is not a result of a decreased transmembrane Na+ gradient after inactivation of Na-K-adenosine triphosphatase (Na-K-ATPase). Although ouabain induced a depolarization similar to that of anoxia, it did not affect EPSP amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Prolongation of gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO).

The effects of 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO), an inhibitor of gamma-aminobutyric acid (GABA) uptake, were examined in the rat hippocampal slice and compared to the actions of the potent GABA uptake inhibitor, cis-4-OH-nipecotic acid. THPO reversibly prolonged GABA-mediated inhibitory postsynaptic potentials (IPSPs) but did not prolong conductance changes evoked by iontophoresed GABA. In contrast, cis-4-OH-nipecotic acid prolonged responses to iontophoresed GABA but had little effect on IPSPs. THPO reduced the intensity of spontaneous epileptiform bursts observed in elevated (8.5 mM) potassium; this effect was absent after addition of 100 microM bicuculline. These results suggest that drugs similar to THPO may be useful for enhancing GABA-mediated inhibition, but that THPO acts by a mechanism distinct from that of the GABA uptake inhibitor, cis-4-OH-nipecotic acid.

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