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PubMed1992

Histamine activates chloride conductance in motor neurons of the lobster cardiac ganglion.

1. Individual motor neurons of the lobster cardiac ganglion were voltage clamped with two microelectrodes. Superfusion of histamine evoked a concentration-dependent membrane current. The mean effective concentration (EC50) for the concentration-effect relationship was 28 microM. 2. The amplitude and polarity of the histamine-activated current depended on intracellular and extracellular Cl- concentration. The membrane potential at which the current polarity reversed was a function of the Cl- equilibrium potential. 3. The histamine-activated Cl- conductance was voltage dependent, increasing with depolarization. As a consequence, the histamine-evoked current showed outward rectification. 4. We conclude that histamine activates a Cl- conductance with biophysical properties similar to the crustacean Cl- conductance activated by gamma-aminobutyric acid (GABA) and to the histamine responses described in lobster olfactory and stomatogastric neurons. 5. The response to histamine was competitively inhibited (IC50 = 7 microM) by cimetidine, an H2 subtype inhibitor in mammals. Ranitidine, pyrilamine, chlorpheniramine, diphenhydramine, and cyproheptadine were 50-100 times less potent than cimetidine. Tubocurarine, a Cl- channel blocker, blocked with an IC50 of 20 microM, but picrotoxin did not begin to inhibit the histamine response until concentrations exceeded 0.1 mM. 6. These results suggest that the response cannot easily be classified with the use of the pharmacological categories developed in mammals. Like the Cl(-)-dependent responses to various neurotransmitters in a number of invertebrates, the histamine response in the lobster cardiac ganglion was inhibited by tubocurarine. 7. Both GABA and histamine had similar effects on the motor neurons, but only GABA inhibited pacemaker bursts. In this respect, GABA more resembles the endogenous inhibitory postsynaptic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1978

The mole of pallido-thalamic transmission investigated with intracellular recording from cat thalamus.

Pallido-thalamic transmission was studied by intracellular recording from neurons in the ventrolateral (VL) and ventroanterior (VA) nuclei of the thalamus in cats anesthetized with pentobarbital. Stimulation of the entopeduncular nucleus (ENT) produced short latency, inhibitory postsynaptic potentials in the VL-VA neurons (1.60 ms on average). When stimuli were applied closer to the VL-VA region along the pallido-thalamic pathway, i.e., to the rostral Forel's field, the IPSP latency was significantly reduced. Linear regression analysis of the IPSP latency against conduction distance between different stimulating the recording positions indicated that the IPSP was produced through a monosynaptic pathway at a conduction velocity of 5 to 11 m/s. The neurons which received IPSPs from the ENT distributed in the rostromedial VL and in the rostral VA, whereas relay cells responding only to the contralateral brachium conjunctivum were found in the caudal VL and in the dorsolateral portion of the rostral VL-VA complex. Reciprocal convergence of pallidal and cerebellar impulses were observed in only a small number of cells, which were located in the border between the two neuron groups. Recording of extracellular field potentials and focal stimulation within and around the rostral VL also indicated that the fiber potentials arose from the ENT nucleus and propagated along a bundle of fibers which terminated within the rostromedial VL-VA complex. These results are all explicable by assuming that the entopeduncular neurons are inhibitory in nature and so inhibit thalamic neurons monosynaptically.

Animals↗

PubMed1998

Chloride concentration in cultured hippocampal neurons increases during long-term exposure to ammonia through enhanced expression of an anion exchanger.

The effects of long-term exposure to ammonia on [Cl-]i in cultured hippocampal neurons were examined. Ammonia increased the [Cl-]i time- (>/=24 h) and concentration- (>/=2 mM) dependently, resulting in a depolarizing shift of the equilibrium potential of the GABAA receptor-Cl- channel opening (EGABA). Such an effect of ammonia was diminished by the inhibitors of Cl-/HCO3- exchangers, 0.1 mM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 0.1 mM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and a carbonic anhydrase inhibitor, 2 mM acetazolamide, but not by a Na+/K+/2Cl-cotransport inhibitor, 50 microM bumetanide, suggesting an enhanced Cl-/HCO3- exchange activity by ammonia. The ammonia-induced increase in [Cl-]i was also abolished by the inhibitors of protein kinase C (PKC), 0.1 microM calphostin C and 10 microM 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine dihydrochloride (H-7), and of transcription and de novo protein synthesis, 1 microM actinomycin D and 0.5 microg/ml cycloheximide, while a PKC activator, 0.1 h microM phorbor 12-myristate 13-acetate (PMA), increased the [Cl-]i. The mRNA level of the AE3 Cl-/HCO3- exchanger was increased by ammonia in a calphostin C- and H-7-sensitive manner. The AE3-like immunoreactivity was also increased by ammonia. These findings suggest that long-term exposure to ammonia increases the expression of AE3 through the activation of PKC, resulting in an increase in [Cl-]i in neurons and a reduction of inhibitory postsynaptic potentials.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1991

Influence of stimulus repetition rate on cortical somatosensory potentials evoked by median nerve stimulation: implications for generation mechanisms.

Despite growing clinical and experimental interest in the cortical components of somatosensory evoked potentials (SEPs) little is known about their physiological dynamics, e.g. with changing stimulation parameters. This paper reports the influence of varying stimulus repetition rate from 0.5 to 5 Hz on cortical SEPs up to 60-msec latency after right median nerve stimulation, separately analyzed at frontal (F3), central (C3) and parietal (P3) electrodes. The amplitudes of early frontal P20 and N25, central P14 and N18, and parietal N20 did not change with stimulation rate. Later deflections were significantly modified when their amplitudes were determined with respect to the baseline: at F3 negative N30 and N60 diminished and positive P40 was enhanced with increasing rate of stimulation. At P3 the effects were the reverse, so that positive P27 and P45 were attenuated while negative N34 and N60 were enhanced. At C3 both positive P22 and P40 and negative N60 were reduced. However, the corresponding peak-to-peak amplitudes changed much less. We conclude that SEP waveforms following the earliest cortical deflections are very sensitive to small changes in stimulation frequency. The opposite changes at F3 compared with P3 probably represent the opposite scalp field poles from horizontally oriented generator(s) located within the primary sensorimotor cortex (SMI). We suggest that the rate effects are partly due to selective sensitivity of postexcitatory inhibitory postsynaptic potentials to stimulation frequency.

Adult↗

PubMed1996

GABAA receptor function in developing rat thalamic reticular neurons: whole cell recordings of GABA-mediated currents and modulation by clonazepam.

1. Nucleus reticularis thalami (NRT) is a nucleus composed entirely of GABAergic neurons, which functions as a pacemaker to synchronize thalamocortical oscillations. To study the functional properties of GABAergic inhibition mediated through activation of gamma-aminobuturic acid-A (GABAA) receptors in these cells, neurons were isolated acutely from NRT at various postnatal developmental stages and recorded from using whole cell patch-clamp techniques. 2. Application of GABA to NRT neurons elicited a large, bicuculline sensitive current with an average reversal potential of -60.6 +/- 1.9 mV (mean +/- SD) in postnatal day (p) 19-21 neurons and -51.2 +/- 3.1 mV in p7 neurons, presumably mediated through activation of a GABAA-mediated chloride conductance. The potency of GABA in activating GABAA receptors decreased significantly with postnatal development in NRT neurons and was best fitted with EC50s of 24.9, 33.9, and 67.2 microM, in neurons isolated from p5-9, p18-25, and p58-74 rats, respectively. The density of GABAA receptors in the membranes of NRT neurons increased significantly with postnatal development. In addition, the GABA current decay rate slowed significantly in neurons isolated from older animals relative to early postnatal rat pups. 3. Both the potency and efficacy of benzodiazepine augmentation of GABAA responses in NRT neurons increased significantly with development. The EC50 of clonazepam decreased from 26 to 6 nM in p5-9 and p58-74 NRT neurons, respectively, whereas the efficacy increased from 126 to 163% augmentation over the same developmental range. 4. The elevated efficacy of clonazepam (CNZ) in NRT neurons relative to thalamic and cortical neurons, particularly in neurons isolated from adult (> p58) rats, is consistent with the anticonvulsant profile of this drug in controlling Generalized Absence epilepsy. Augmenting inhibition within NRT would enhance NRT/ NRT inhibitory connections and thereby decrease the amplitude of NRT-mediated synchronizing inhibitory postsynaptic potentials onto thalamus (where CNZ has low efficacy), in turn making it more difficult to elicit burst firing in thalamus due to deinactivation and subsequent activation of the low-threshold Ca2+ current. 5. The present developmental profile of GABAA responses in GABAergic NRT neurons provides data important in understanding the role of GABAergic inhibition within NRT in the modulation of normal and pathological thalamocortical rhythms in the brain and is also relevant in understanding potential differences in GABAA receptor physiology and pharmacology in GABAergic interneurons relative to glutamatergic neurons.

Aging↗

PubMed1996

Presynaptic GABAB receptors modulate IPSPs evoked in neurons of deep cerebellar nuclei in vitro.

1. Recording from deep cerebellar nuclei neurons, we investigated the role of presynaptic gamma-aminobutyric acid-B (GABAB) receptors in the modulation of monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of Purkinje cells in rat slice cultures. 2. Bath application of the GABAB receptor agonist, baclofen (10 and 100 microM) induced two effects in cerebellar nuclei neurons: a postsynaptic hyperpolarization of 4.2 +/- 1.7 (SD) mV and a reduction in the amplitude of evoked IPSPs (30 +/- 10%). 3. When the postsynaptic GABAB response was blocked by filling the electrode with cesium methanesulfonate (2 M), or with a solution containing QX 314 (50 mM), bath application of baclofen (10 microM) reversibly depressed the evoked IPSPs by 36.7 +/- 18.7% and 42 +/- 20.3%, respectively. Under these experimental conditions, baclofen (10 microM) also reduced the amplitude of spontaneous IPSPs (10.2 +/- 9.5%) and decreased their frequency by 45.6 +/- 8.8%, suggesting a presynaptic site of action. 4. The presynaptic action of baclofen was not due to activation of receptors on the somata of Purkinje cells: baclofen (100 microM) failed to alter membrane holding current in Purkinje cells, and it had no effect on the rate of spontaneous action-potential discharge in Purkinje cells in the presence of ionotropic glutamate receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione, 20 microM; D-2-amino-5-phosphonovalerate, 40 microM). 5. IPSPs could be evoked by extracellular stimulation of the Purkinje cell layer or by direct stimulation of the fiber bundle connecting Purkinje cells to deep cerebellar neurons. In both situations, baclofen (10 microM) reduced the amplitude of evoked IPSPs by 32.7 +/- 8.8% and 31.2 +/- 10.2%, respectively. 6. These results demonstrate that GABAB receptors are present on the terminals of Purkinje cells. Their activation causes a decrease in the amplitude of evoked IPSPs recorded in deep cerebellar nuclei and also reduces the frequency of spontaneous inhibitory events.

Animals↗

PubMed2003

Modulation of inhibitory autapses and synapses on rat CA1 interneurones by GABA(A) receptor ligands.

To determine whether autaptic inhibition plays a functional role in the adult hippocampus, the action potential afterhyperpolarisations (spike AHPs) of CA1 interneurones were investigated in 25 basket, three bistratified and eight axo-axonic cells. The spike AHPs showed two minima in all regular-spiking (5), burst-firing (3) and in many fast-spiking cells (17:28). The fast component had a time-to-peak (TTP) of 1.2 +/- 0.5 ms, the slower TTP was very variable (range of 3.3-103 ms). The AHP width at half-amplitude (HW) was 12.5 +/- 5.7 ms in fast-spiking, 29.3 +/- 18 ms in regular-spiking and 99.7 +/- 42 ms in burst-firing cells. Axo-axonic cells never establish autapses, and the fast-spiking variety showed narrow (HW: 3.9 +/- 0.7 ms) spike AHPs with only one AHP minimum (TTP: 0.9 +/- 0.1 ms). When challenged with GABA(A) receptor modulators, spike AHPs in basket and bistratified cells were enhanced by zolpidem (HW by 18.4 +/- 6.2 % in 10:15 cells tested), diazepam (45.2 +/- 0.5 %, 6:7), etomidate (43.9 +/- 36 %, 6:8) and pentobarbitone sodium (41 %, 1:1), and were depressed by bicuculline (-41 +/- 5.7 %, 5:8) and picrotoxin (-54 %, 1:1), and the enhancement produced by zolpidem was reduced by flumazenil (-31 +/- 13 %, relative to the AHP HW during exposure to zolpidem, 3:4). Neuronal excitability was modulated in parallel. The spike AHPs of three axo-axonic cells tested showed no sensitivity to etomidate, pentobarbitone or diazepam. Interneurone-to-interneurone inhibitory postsynaptic potentials (IPSPs), studied with dual intracellular recordings, had time courses resembling those of the spike AHPs. The IPSP HW was 13.4 +/- 2.8 ms in fast-spiking (n = 16) and 28.7 +/- 5.8 ms in regular-spiking/burst-firing cells (n = 6), and the benzodiazepine1-selective modulator zolpidem strongly enhanced these IPSPs (45 +/- 28 %, n = 5). Interneurones with spike AHPs affected by the GABA(A) receptor ligands exhibited 3.8 +/- 1.9 close autaptic appositions. In three basket cells studied at the ultrastructural level 6 of 6, 1 of 2 and 1 of 2 close appositions were confirmed as autapses. Therefore, in the hippocampus autaptic connections contribute to spike AHPs in many interneurones. These autapses influence neuronal firing and responses to GABA(A) receptor ligands.

Action Potentials↗

PubMed2006

Unitary IPSPs enhance hilar mossy cell gain in the rat hippocampus.

Mechanisms that control neuronal gain allow for adaptive rescaling to synaptic inputs of varying strengths or frequencies. Here, we show that unitary IPSPs (uIPSPs) modulate gain and unitary EPSP (uEPSP)-action potential coupling in mossy cells (MCs) from rat hippocampal slices. Mossy fibre-evoked uEPSCs were large, facilitated and were suppressed by the group II metabotropic glutamate agonist LY354740. Conversely, uIPSCs were smaller, depressed and were not affected by LY354740, but exerted strong inhibitory control over uEPSP-action potential coupling. The IPSC reversal potential was determined by gramicidin perforated patch recordings to be -65.3 +/- 5.0 mV, lying between the resting membrane potential (-75.3 +/- 1.1 mV) and the action potential threshold (-56.5 +/- 2.4 mV). When applied at theta frequency (10 Hz), uIPSPs increased the offset of the MC input-output response to depolarizing current injection, but also increased gain, maximal firing rate and the slope of the depolarization preceding action potentials. These effects were unchanged by the Ca2+ and HCN channel blockers mibefradil and ZD7288, respectively. The height and maximal slope of MC action potentials during tonic depolarization were also increased by uIPSPs, and the decay of uIPSP conductances injected by dynamic clamp at subthreshold membrane potentials was prolonged by TTX. Application of the muscarinic agonist pilocarpine mimicked the effect of IPSPs on MC maximal firing rate, and action potential height and slope, and this was reversed by the GABA(A) antagonist gabazine. Thus, uIPSPs can increase neuronal gain under hyperexcitable conditions, and this effect is probably due to the de-inactivation of a TTX-sensitive voltage-dependent Na+ conductance.

2-Amino-5-phosphonovalerate↗

PubMed1988

Characteristics of local excitatory circuits studied with glutamate microapplication in the CA3 area of rat hippocampal slices.

1. Local neuronal circuits in CA3 of hippocampal slices were studied by recording excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) intracellularly during glutamate microapplication in CA3. Control experiments validated this approach by providing evidence that glutamate microdrops stimulated neurons but not axons-of-passage or axon terminals in CA3. 2. Glutamate microdrops (10-20 mM, 10-20 microns diam) increased the firing frequency of extracellularly recorded dentate granule cells for 5-10 s when applied to their somata but not when applied to their mossy fiber axons and terminals in the hilus and in CA3. 3. Glutamate microapplications to granule cell somata, but not to mossy fiber axons, also increased the frequency of intracellularly recorded EPSPs in CA3 pyramidal cells for 5-10 s. This provided a second line of evidence that glutamate did not cause firing in mossy fiber axons synapsing in CA3. 4. In slices where the CA3 region was surgically separated from the dentate gyrus and CA2, glutamate microdrops placed in the CA3 stratum pyramidale within 400 microns of intracellularly recorded pyramidal cells increased the frequency of EPSPs and IPSPs. Tetrodotoxin (1 microgram/ml) blocked these increases in PSP frequency, indicating that they did not result from glutamate-induced depolarization and associated transmitter release from presynaptic terminals. Increases in PSP frequency were interpreted to reflect glutamate activations of CA3 neurons with local synaptic connections to recorded cells. 5. Low concentrations of picrotoxin (PTX, 5-10 microM) blocked glutamate-induced increases in IPSP frequency and often revealed increases in EPSP frequency where they were not previously observed. This suggests that recurrent inhibitory circuits normally mask or block transmission through recurrent excitatory pathways in CA3. 6. In five experiments following PTX treatment (7.5-10 microM), large and prolonged (up to 2 min) increases in EPSP frequency were observed in CA3 pyramidal cells to glutamate microapplications in CA3. Rhythmic epileptiform bursts eventually occurred in two of these cases, suggesting that the protracted increases in EPSP frequency represent a form of reverberating excitation during a transition from normal to epileptic states. 7. Sixteen CA3 pyramidal cells were recorded in PTX (5-10 microM) during glutamate microapplications at 200 and 400 microns on each side of the recording site. The most consistent glutamate-induced increases in EPSP frequency occurred to microapplications 200 microns from recording sites on the hilar side.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Opposing effects of striatonigral feedback pathways on midbrain dopamine cell activity.

The existence of a striatonigral GABAergic pathway has been well established both anatomically and biochemically. During intracellular recording from identified DA neurons in vivo, stimulation of the striatum (100 microA, 50 microseconds pulses) elicits an inhibitory postsynaptic potential (IPSP) and a rebound depolarization. The IPSP is a short latency (1.8-2.2 ms) conductance increase to chloride, since: the reversal potential is near the chloride reversal potential reported for other cells (-68 mV); intracellular chloride injection progressively reverses the IPSP into a depolarization with a similar time course; and the response of DA cells to systemic injection of the chloride channel blocker, picrotoxin, also exhibits a similar reversal potential. In contrast, during extracellular recording, stimulation of the striatum at low levels of intensity (e.g. 20 microA at 10 Hz) increases the firing rate of DA cells. Stimulation of the striatum will, in addition, elicit IPSPs in a subclass of substantia nigra zona reticulata neurons at the same latency as the IPSPs triggered in DA cells. These IPSPs also reverse with intracellular chloride injection. However, their amplitude is larger and their duration longer than observed in DA cells, and there is no depolarizing rebound. The late component of the IPSP in the zona reticulata neurons corresponds temporally to the rebound depolarization seen in DA cells in response to striatal stimulation. In addition, when recorded extracellularly, striatal stimulation will inhibit the firing of this class of zona reticulata interneurons at the same stimulation parameters that will excite DA cells. These data suggest that striatal cells may send branched fast-conducting GABAergic projections to zona reticulata cells and DA cells. Furthermore, low levels of striatal stimulation can excite DA cells by preferentially inhibiting interneurons in the zona reticulata which are more sensitive to the inhibitory effects of GABA than are DA neurons.

Animals↗

PubMed1994

Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering.

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1-5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Probabilistic determination of synaptic strength.

This work was carried on to analyze the presynaptic components of synaptic efficacy, which is designated by the term of synaptic strength. To assess the relations between synaptic strength and innervation density, the properties of unitary Cl(-)-dependent inhibitory postsynaptic potentials (IPSPs) evoked in the potentials (IPSPs) evoked in the goldfish Mauthner (M-) cell by single impulses in individual presynaptic cells, including quantal release parameters, were compared with the histological features of the same neurons, determined from their reconstructions after intracellular injection with horseradish peroxidase (HRP). Because the M-cell is a stereotyped target neuron, comparison of the synaptic strength from different experiments was accomplished by using as a quantitative measure of this parameter the mean unitary IPSP amplitude normalized with respect to the reversal potential for Cl- (i.e., the driving force). In 108 experiments at low stimulus frequency, the majority of the normalized responses (63%) were grouped in a rather narrow range, varying about fourfold, or from 1.5 to 6% of the driving force, with results from stained (n = 46) and unstained (n = 62) cells being the same. In contrast, for the same restricted set of responses, the number of presynaptic terminals (histological n) encompassed a larger range, varying from 3 to 52. Impulses in neurons with quite different complements of terminal boutons could evoke similarly sized, normalized IPSPs, and these two parameters were poorly correlated, with there being, at most, a tendency for the responses to increase with histological n for small values of the latter. Quantal fluctuations in IPSP amplitudes were analyzed according to a binomial model having three parameters, p, which is the probability of release, n, which is the number of releasing units and was previously shown to equal the number of presynaptic boutons or active sites, and q, or the quantal size. The normalized quantal size varied randomly, with a mean value of 0.51% (SD = 0.20) and was relatively independent of n. In contrast, the distribution of p, which ranged from 0.17 to 0.74 (mean = 0.40, SD = 0.155), was skewed to the right; this parameter tended to decrease as a function of increasing n. The normalized unitary inhibitory conductance (g'IPSP) underlying an IPSP is equal to the product of npg'q, where g'q is the normalized quantal conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1983

Neuronal pathways for activation of inhibitory interneurons in pyriform cortex of the rabbit.

The neuronal pathways responsible for the fast inhibitory postsynaptic potentials (IPSPs) elicited in principal cells in the pyriform cortex (PC) by volleys from the olfactory bulb (OB), the lateral olfactory tract (LOT), the anterior commissure (AC), and the deep-lying structures of the PC (DPC) were studied in the rabbit. The central latencies of the fast IPSPs (measured from the onset of the monosynaptic excitatory postsynaptic potential (EPSP) elicited by volleys through the LOT) ranged between 3.0 and 9.3 ms (5.5 +/- 1.3 (SD) ms; n = 54) in the case of OB shocks and between 4.5 and 6.5 ms (5.1 +/- 0.7 (SD) ms; n = 7) in the case of LOT shocks. The onset latencies of the fast IPSPs were between 2.5 and 11.8 ms (5.1 +/- 1.8 (SD) ms; n = 66) in the case of DPC shocks and between 3.5 and 10.1 ms (5.8 +/- 1.5 (SD) ms; n = 61) in the case of AC shocks. The conditioning OB or LOT shocks almost completely eliminated the LOT-evoked fast IPSP when the testing shock was applied at the peak period of the conditioning slow IPSP. The conditioning OB shocks also eliminated the initial part of the OB-evoked fast IPSP, leaving the later part of the fast IPSP almost unchanged. Thus, the onset latency of the OB-evoked fast IPSP was lengthened by 7.1 +/- 2.9 (SD) ms (n = 35) by the conditioning OB shock. The conditioning OB or DPC shocks left the peak amplitude of the DPC-evoked fast IPSP almost unaffected. Similarly, the conditioning OB or AC shocks left the peak amplitude of the AC-evoked fast IPSP almost unaffected. The conditioning OB, DPC, or AC shocks had only a slight influence on the onset latency of the DPC- or AC-evoked fast IPSPs. Rhythmical steps at intervals of 3-5 ms were observed in the rising phase of the OB-evoked fast IPSP. This was interpreted as a result of a repetitive impingement of interneuronal discharges on the impaled cells. Spatial facilitation was observed among the fast IPSPs evoked by volleys from the OB, DPC, and AC when shocks were applied at suitable intervals. A slight facilitation was also seen between the LOT-evoked fast IPSP and the DPC- or AC-evoked fast IPSP. These results were interpreted as a result of the convergence of excitatory synaptic inputs onto the presumed inhibitory interneurons from the four structures of the brain. A temporal facilitation of the fast IPSPs was observed when the OB, DPC, or AC shocks were applied repetitively at short intervals. This suggests a temporal facilitation of the spike discharges of the presumed inhibitory interneurons under similar conditions. From these results, criteria were determined for identifying the inhibitory interneurons.

Animals↗

PubMed1991

Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices.

1. gamma-Aminobutyric acid (GABA)-mediated, Cl(-)-dependent inhibitory postsynaptic potentials (IPSPs) and GABA currents in immature rat hippocampal CA1 neurones were studied using the whole-cell recording technique in brain slices. 2. IPSPs evoked by electrical stimulation were observed in postnatal 2- to 5- (PN2-5), 8- to 13-(PN8-13) and 15- to 20-(PN15-20)day-old CA1 neurones. In the presence of glutamate receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonovaleric acid (APV), the reversal potential for the IPSP (EIPSP) was near the resting membrane potential (RMP) in the PN2-5 neurones, but 13 and 25 mV more negative than the RMP in PN8-13 and PN15-20 neurones respectively. IPSPs and GABA currents were blocked by the GABAA-receptor antagonists bicuculline or picrotoxin. 3. The reversal potential for somatic GABA currents (EGABA) was examined in the presence of tetrodotoxin (TTX). There was a strong dependence of the EGABA upon the patch pipette [Cl-] ([Cl-]p). indicating that the GABA currents were mediated by a Cl- conductance. In PN2-5 neurones, EGABA agreed with the value predicted by the Goldman-Hodgkin-Katz equation at given concentrations of internal and external anions permeable through GABA-activated Cl- channels, whereas EGABA in older neurones was 8-18 mV more negative. 4. Examination of the relations between EGABA, holding potential, [Cl-]p and resting conductance indicated that the membrane of the PN2-5 neurones was readily permeable to Cl- which followed a passive Donnan equilibrium. Passive distribution of Cl- played a decreasing role in PN8-13 neurones and in PN15-20 neurones. 5. To assess the contribution of outward Cl- co-transport, bath applications of high K+ or furosemide were performed. High K+ and furosemide caused a reversible positive shift of EGABA in PN15-20 neurones. Raising the temperature moved EGABA to a more negative potential, with a Q10 of 5 mV. A similar change of EGABA in response to high K+, but not to furosemide, was found in PN8-13 neurones. 6. The present data indicate the existence of GABAA-mediated inhibitory synaptic connections in CA1 neurones at the earliest stages of postnatal life. During the first postnatal week, Cl- ions are passively distributed and the EIPSP and EGABA are near the RMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Loss of spontaneous blinking in a patient with Balint's syndrome.

A patient with Balint's syndrome caused by bilateral parieto-occipital lesions lost spontaneous blinking, suggesting that humans, like nonhuman primates, have parietal lobe neurons that are important for blinking. Although the functions of spontaneous blinking are not known, they may help initiate some saccades and, like saccades, be involved in the cancellation of thalamic inhibitory postsynaptic potentials, thereby facilitating processing of new foveal targets. Spontaneous blinking may also facilitate sensory relay during sustained attention and, therefore, help prevent fading of a retinal image.

Adult↗

PubMed2006

Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAA receptor-mediated mechanisms.

The epilepsy that occurs in SSADH deficiency has a seizure phenotype similar to that occurring in the SSADH(-/-) mouse. We examined the expression and function of the GABA(A) receptor (GABA(A)R) in SSADH-deficient mice. A selective decrease in binding of [(35)S]tert-butylbicyclophosphorothionate was observed in SSADH(-/-) mice at postnatal day 7 that was progressive until the third postnatal week of life when, at the nadir of the decreased [(35)S]tert-butylbicyclophosphorothionate binding, generalized convulsive seizures emerged that rapidly evolved into status epilepticus. We also observed a substantial downregulation of the beta(2) subunit of GABA(A)R, a reduction in GABA(A)-mediated inhibitory postsynaptic potentials, and augmented postsynaptic population spikes recorded from hippocampal slices. The SSADH(-/-) mouse model represents a powerful investigative tool for understanding the pathophysiology of the seizures associated with human SSADH deficiency. These data raise the possibility that progressive dysfunction of the GABA(A)R may be involved in the development of seizures in SSDAH-deficient mice. Elucidation of the precise fundamental mechanisms of the perturbation of the GABA(A)R-mediated function in SSADH(-/-) mice could lead to the development of novel treatment modalities designed to reduce the neurological morbidity in children with SSADH deficiency.

Animals↗

PubMed1983

Studies of human and monkey "epileptic" neocortex in the in vitro slice preparation.

The in vitro slice technique was used to study neuronal activity in human cortical tissue removed during neurosurgical procedures for intractable epilepsy and in monkey neocortex rendered epileptogenic by injection of alumina gel. In both cases, biopsies were guided by electrocorticographic signs of epileptiform activity. Intracellular recordings were made from 167 neurons in human tissue and from 73 neurons in monkey tissue samples. There was little spontaneous activity in these biopsies and no indication of spontaneous cellular bursting. Stimulation at the pial surface or in white matter evoked synaptically driven activity that was primarily excitatory. Graded bursts of activity could be elicited from some cells, but no all-or-none paroxysmal depolarization shifts were recorded. Inhibitory postsynaptic potentials were relatively rare. Intracellular injections of dye in a small number of neurons revealed no obvious differences between bursting and nonbursting neurons. These in vitro studies of chronic epileptic cortex have thus far provided few clear insights into the basic mechanisms of epilepsy.

Action Potentials↗

PubMed1982

An intracellular HRP study of the rat globus pallidus. I. Responses and light microscopic analysis.

A study of the intracellularly recorded responses of rat globus pallidus neurons to activation of striopallidal fibers was combined with light microscopic examination of the morphology of these same neurons using intracellular horseradish peroxidase. The response to stimulation of caudate-putamen is an inhibitory postsynaptic potential with observed latencies ranging from 5.1 to 9.8 msec. These values correspond to conduction velocities of 0.4 to 0.8 m/second for striopallidal fibers. Comparison with extracellular controls shows no excitatory component to the response. All recovered and analyzed neurons (n = 11) were of the large type of pallidal neuron known from Golgi studies but the addition that two subtypes could be recognized. Large neurons located medially in the nucleus had dendritic fields with large dorsoventral extent (ca. 1 mm) when compared to their mediolateral and rostrocaudal dimensions (ca. 0.4 mm) and these neurons emitted no axon collaterals. Large neurons located laterally in the nucleus had disklike dendritic fields with both dorsoventral and rostrocaudal dimensions being on the order of 1 mm but with a minor axis of approximately 100 micrometers. The axons of these neurons possessed collaterals. As a consequence of their disk-shaped dendritic field, neurons belonging to the laterally placed subgroup and occupying the narrow (ca. 100 micrometers thick) striopallidal border zone known to receive a distinct input from neostriatum have dendrites restricted to that zone.

Afferent Pathways↗