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PubMed1991

Effects of calcium channel agonist and antagonists on calcium-dependent events in CA1 hippocampal neurons.

The effects of a variety of calcium channel modulators on different calcium-dependent events in CA1 pyramidal hippocampal neurons were analysed using intracellular recordings in an in vitro slice preparation. The following substances were tested: the dihydropyridine calcium agonist BAY K 8644, the dihydropyridine calcium antagonist nimodipine, the phenylalkylamine verapamil and the snail toxin omega-conotoxin GVIA (omega-CgTx). BAY K 8644 increased the repolarization time of the after hyperpolarization (AHP) following a spike burst. This effect was antagonized by nimodipine. BAY K 8644 also prolonged the calcium spike and, in some cases, increased the size of the synaptic events resulting from activation of the Schaffer collateral/commissural system. Nimodipine decreased the size of the AHP in some neurons but had no consistent effect on synaptic events. Verapamil at low concentrations (1-10 microM) had no significant effects on the calcium-dependent events in the hippocampus. Increasing the concentration (up to 100 microM) led to a progressive suppression of the AHP and of the slow inhibitory postsynaptic potential (IPSP), probably via an action on potassium conductances. In addition, the baclofen-induced hyperpolarization was blocked by verapamil. Interestingly, at this higher concentration, verapamil could suppress the AHP without depressing the calcium spike. omega-CgTx selectively blocked the synaptic events (especially the IPSPs) but had no effect on non-synaptic events. This last compound exhibits a high degree of selectivity, acting on N-type calcium channels which are involved in neurotransmitter release. Our results provide evidence that different classes of agents which act on calcium channels can be used to discriminate between different calcium-dependent responses in CA1 hippocampal neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1977

Effects of dibutyryl cyclic adenosine 3',5'-monophosphate and theophylline on the bullfrog sympathetic ganglion cells.

1 Effects of dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) and theophylline on bullfrog sympathetic ganglion cells were examined in order to test the hypothesis that cyclic AMP is essential for the generation of slow inhibitory postsynaptic potentials (i.p.s.ps) in these cells. 2 In the absence or presence of theophylline, dibutyryl cyclic AMP did not hyperpolarize but rather tended to depolarize ganglia that were hyperpolarized by adrenaline. 3 Theophylline augmented neither the P-potential (slow i.p.s.p.) nor adrenaline-induced hyperpolarization. 4 Thus, cyclic AMP does not seem to be essential for the generation of the slow i.p.s.p., at least in amphibian sympathetic ganglion cells.

Animals↗

PubMed1986

Alpha 2-adrenergic hyperpolarization is not involved in slow synaptic inhibition in amphibian sympathetic ganglia.

The adrenaline-induced hyperpolarization (AdH), slow inhibitory postsynaptic potential (slow i.p.s.p.) and hyperpolarizing phase of the response to methacholine (MChH) in Rana pipiens sympathetic ganglia were studied by means of the sucrose-gap technique. Desmethylimipramine (DMI, 0.5 microM) lowered the EC50 for adrenaline from 1.65 microM (1.23-2.21 microM, n = 10) to 0.30 microM (0.21-0.41 microM, n = 8). DMI did not potentiate the slow i.p.s.p. or the MChH. Propranolol, sotalol or prazosin (1 microM) did not antagonize the AdH. The response was antagonised by phentolamine (IC50 = 0.53 microM), yohimbine (IC50 = 6.2 nM) and idazoxan (IC50 = 0.59 microM). Yohimbine (0.1 microM) did not reduce the amplitude of the slow i.p.s.p. or the MChH. The slow i.p.s.p. was eliminated in Ringer solution containing Cd2+ (100 microM). This concentration of Cd2+ did not reduce the amplitude of the MChH. Alpha-Methylnoradrenaline produced a concentration-dependent hyperpolarization with an EC50 of 0.31 microM (0.13-0.73 microM, n = 5), in the presence of DMI (0.5 microM). These results are consistent with the hypothesis that the AdH may be generated by activation of a receptor similar to the mammalian alpha 2-adrenoceptor. No evidence was found in support of the hypothesis that an adrenergic interneurone is involved in the synaptic pathway for the slow i.p.s.p.

Adrenergic alpha-Agonists↗

PubMed1992

Changes in intrinsic inhibition in isolated hippocampal slices during ethanol withdrawal; lack of correlation with withdrawal hyperexcitability.

1. Intracellular recordings were made from pyramidal cells in area CA1 in mouse isolated hippocampal slices, after chronic ethanol treatment in vivo. 2. Fast i.p.s.ps were isolated by injection of the impaled neurones with QX314 (to block fast sodium currents and the slow i.p.s.p.) and stimulating the interneurones in the presence of the glutamatergic blockers, CNQX and APV. 3. The isolated fast-inhibitory postsynaptic potential (f.-i.p.s.p.) was measured at intervals during the 7 h withdrawal period. The reversal potential and sensitivity to bicuculline suggested that the isolated f.-i.p.s.p. was mediated by activation of the GABAA receptor-chloride ionophore complex. 4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of -50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ei.p.s.p., with no observed change in conductance, Gi.p.s.p. 5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings. 6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period. 7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of - 50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ejp.sp with no observed change in conductance, Gj ps p.5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings.6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period.7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.The increase in the f.-i.p.s.p. during the initial stages of the withdrawal might prevent the overt expression of epileptiform activity at this time.

Animals↗

PubMed2000

Synaptic properties of neocortical neurons in epileptic mice lacking the Otx1 gene.

PURPOSE: The murine homeobox-containing Otx gene is required for correct nervous system and sense organ development. Otx1-/1 mice obtained by replacing Otx with the lac Z gene show developmental abnormalities of the cerebellum, mesencephalon, and cerebral cortex associated with spontaneous epileptic seizures (1). The epileptogenic mechanisms accounting for these seizures were investigated by means of electrophysiological recordings made from neocortical slices. METHODS: The 400-microm slices were prepared from the somatosensory cortex of Otx1-/- and Otx1+/+ mice, and the current clamp intracellular recordings were obtained from layer V pyramidal neurons by means of pipettes containing K+ acetate 1.5 mol/L and biocytin 2% (pH 7.3). RESULTS: Synaptic responses could be evoked in the neocortical pyramidal neurons by electrically stimulating the underlying white matter. gamma-Aminobutyric acid A/B-mediated inhibitory postsynaptic potentials were more pronounced in the Otx1-/- than in the control pyramidal neurons from the earliest postnatal period; multisynaptic excitatory postsynaptic potentials were significantly more expressed in the Otx1-/- mice also at the end of the first postnatal month, when they were only rarely encountered in controls. CONCLUSION: Excessive excitatory amino acid-mediated synaptic driving may lead to a hyperexcitable condition that is responsible for the epileptic manifestations occurring in Otx1-/- mice. This excess of excitation is not counteracted by well-developed gamma-aminobutyric acid activity, which seems to be involved in the synchronization of cell discharges. Our ongoing and more extensive comparative analysis of the mutants and controls should help to clarify the way in which the putative rearrangement taking place in Otx1-/- neocortex may lead to the excitatory hyperinnervation of layer V pyramidal neurons.

Animals↗

PubMed1986

Effects of acute ethanol administration on neocortical inhibition.

The hypothesis that acutely administered ethanol could interfere with neocortical recurrent inhibition (RI) was supported. The large surface negative wave in response to antidromic stimulation of the cerebral peduncle represents a summation of inhibitory postsynaptic potentials, a measure of RI. In acute experiments on adult rats, blood alcohol levels of less than about 120 mg/100 ml slightly facilitated the surface negative wave. Higher blood alcohol levels always blocked the surface negative response. Stimulation of the somatosensory thalamic relay nuclei produced a cortical response on which ethanol had a moderate blocking effect. Conditioning-test procedures revealed that cerebral peduncle stimulation strongly blocked the thalamocortical (test) response, especially after ethanol, but thalamic stimulation (conditioning) had no effect upon the surface negative wave. This demonstrates a differential effect on the two cortical processes. Cortical RI seems to be especially sensitive to blood alcohol level, but the function of cortical RI is complex. By way of acting on RI, ethanol likely affects control of sensory input and cortical sensory organization as well as selectivity and magnitude of motor discharge.

Afferent Pathways↗

PubMed1993

Cholinergic and non-cholinergic synaptic mechanisms in the aged rat hippocampus.

We compared age-related alterations in the electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons in three strains of rats (Sprague-Dawley, Fisher 344 and Wistar) at 3-4 and 25-32 months of age, using the in vitro slice preparation. The most consistent age-related alterations were: a decrease in membrane excitability, a decrease in the amplitude and duration of inhibitory postsynaptic potentials and a decreased sensitivity to the effect of the cholinergic agonist carbachol. In contrast, no consistent alterations in calcium-dependent events were observed in these strains of rats. The age-related changes in the duration of the after-hyperpolarization (AHP) were different (and even opposite) depending on the strain studied. Our results show that age-related changes observed in a given strain are not necessarily present in all strains of the same species.

Aging↗

PubMed1998

GABAergic mechanisms that shape the temporal response to odors in moth olfactory projection neurons.

Mitral/tufted cells in the olfactory bulb and projection neurons (PNs) in the insect antennal lobe are involved in complex synaptic interactions with inhibitory interneurons to help shape their odor-evoked responses. In the moth Manduca sexta, both gamma-aminobutyric acid (GABA) and the GABAA receptor agonist muscimol hyperpolarize and lower input resistance in many PNs, often blocking ongoing spike traffic. The GABA response mimics a short-latency, chloride-mediated inhibitory postsynaptic potential (IPSP) evoked in PNs by electrical or odor stimulation of afferent inputs, and the classical GABAA receptor antagonist bicuculline methiodide (BMI) quickly and reversibly blocks this IPSP. Focal injection of BMI (100 microM) immediately preceding a GABA pulse blocks the hyperpolarization evoked by GABA, but a similar injection of BMI preceding an acetylcholine (ACh) pulse fails to block the depolarization evoked by ACh. Moreover, the temporal pattern of odor-evoked activity in moth PNs is also strongly and reversibly altered by BMI. Importantly, the temporal pattern of the response depends on the temporal characteristics of the stimulus: continuous stimulation evokes more complex, rhythmic responses, whereas a pulsatile stimulus can be copied with a discrete burst of spikes for each pulse. Collectively our results indicate that PNs in the moth antennal lobe possess GABA receptors that share certain characteristics in common with vertebrate GABAA receptors. These receptors are largely responsible for helping PNs integrate information about both the molecular features and the timing of olfactory input to the brain.

Animals↗

PubMed1994

Presynaptic inhibition by neuropeptide Y of slow inhibitory synaptic transmission in submucous neurones of guinea-pig caecum.

The occurrence and disposition of immunoreactivity for neuropeptide Y (NPY) was investigated in the submucosa of guinea-pig caecum. There were few NPY-immunoreactive neurones but intraganglionic varicose fibres were so numerous and strongly immunoreactive that some somata may have been obscured. In each neurone tested, exogenous application of NPY (1-100 nM) depressed the duration and amplitude of the slow inhibitory postsynaptic potential. In contrast, NPY (1-300 nM) had no effects on the resting membrane potential, input resistance and fast and slow excitatory synaptic transmission.

Animals↗

PubMed1988

Outward rectification of inhibitory postsynaptic currents in cultured rat hippocampal neurones.

1. Inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) were recorded from cultured hippocampal neurones of the embryonic rat at 22 degrees C, using the whole-cell patch-clamp technique with a low-Cl-, 145 mM-potassium gluconate solution in the patch pipette. Individual synaptic events were elicited at low frequency (0.05-0.1 Hz) by stimulating a presynaptic neurone either by direct intracellular current injection, or by applying a brief pulse of L-glutamate. 2. In target neurones voltage clamped at -40 mV, outwardly directed IPSCs of mean amplitude 0.23 nA were recorded. The IPSCs were depressed by the GABA antagonist bicuculline, and reversed polarity between -50 and -80 mV (mean -64 mV), as did current responses to gamma-aminobutyric acid. The IPSPs and IPSCs reversed as a single phase; no bicuculline-resistant 'late' synaptic event was observed. 3. The IPSCs had variable kinetics, with rise times between 1 and 5 ms (mean 2.9 ms) at -40 mV, and slower, monoexponential, decay phases (decay time constant, tau IPSC, 10-40 ms at -40 mV). In some cells, tau IPSC clearly increased with depolarization. 4. The IPSC reversal potential was -64 +/- 9 mV (n = 23) under the experimental conditions used; this suggests that the synaptically activated channels are approximately 25 times more permeable to Cl- than to the gluconate anion. 5. The peak conductance associated with the IPSC showed outward rectification. The synaptic conductance measured at -40 mV was 1.7 times greater than that measured at -100 mV; at -20 mV, synaptic conductance was 2.5 times greater than at -100 mV. This outward rectification can be explained by a constant field model under these experimental conditions of asymmetric Cl- concentrations.

Action Potentials↗

PubMed1992

Intracellular electrophysiological study of suprachiasmatic nucleus neurons in rodents: inhibitory synaptic mechanisms.

1. The mechanisms responsible for evoked and spontaneous fast inhibitory postsynaptic potentials (IPSPs) in the hypothalamic suprachiasmatic nucleus (SCN) were studied with intracellular recording. SCN neurons, primarily ones identified as receiving excitatory optic nerve input, were recorded in rat and guinea-pig brain slice preparations maintained in vitro. 2. In normal medium, electrical stimulation of a site dorsocaudal to the SCN evoked IPSPs from thirty-three of thirty-six neurons. The evoked IPSPs rose to the peak quickly (8.7 +/- 0.9 ms, mean +/- S.E.M.; n = 15 neurons) and decayed gradually with a time constant of 25 +/- 3 ms. Spontaneous IPSPs were present in each of the thirty-six neurons. These IPSPs had a rise-to-peak time of 7.2 +/- 1.0 ms (n = 6 neurons) and a decay time constant of 14 +/- 5 ms. 3. When recorded with potassium acetate-filled electrodes, the evoked and spontaneous IPSPs were hyperpolarizing at resting membrane potential (less negative than -70 mV) and had a reversal potential of around -75 mV. On the other hand, when recorded with potassium chloride-filled electrodes, the IPSPs were depolarizing at membrane potentials more negative than -50 mV and had an estimated reversal potential less negative than spike threshold. 4. Bath application of bicuculline (10-50 microM), a gamma-aminobutyric acidA (GABAA) receptor antagonist, resulted in a complete blockade of both the evoked (n = 16) and spontaneous (n = 13) IPSPs. The bicuculline effects were reversible, and were not associated with any significant and consistent change in baseline membrane potential or input resistance. The neurons impaled in bicuculline-containing medium (n = 11) exhibited neither spontaneous IPSPs nor evoked IPSPs. 5. In some neurons bicuculline-resistant hyperpolarizing potentials, which were similar to the fast IPSPs in time course, occurred spontaneously or were evoked by electrical stimulation of the optic nerve or the dorsocaudal site. A fast prepotential always preceded the hyperpolarizing potential, and hyperpolarizing currents blocked these events, indicating that they were not synaptic in origin. No slow IPSPs were detected. 6. The results suggest that fast IPSPs from non-retinal afferents exist in virtually all SCN neurons receiving excitatory retinal input, and that GABAA receptors associated with Cl- channels mediate the fast IPSPs.

Action Potentials↗

PubMed1993

The role of bicarbonate in GABAA receptor-mediated IPSPs of rat neocortical neurones.

1. The ionic mechanism underlying the fast, GABAA receptor-mediated inhibitory postsynaptic potential (IPSPA) was examined in rat neocortical neurones using intracellular recording techniques. Synaptic responses were evoked by orthodromic stimulation applied to the subcortical white matter or to the pial surface. All experiments were carried out at a constant extracellular Cl- concentration. 2. The resting membrane potential was -76.2 +/- 1.0 mV (mean +/- S.E.M., n = 32) and in most cells IPSPA was depolarizing. The reversal potential of IPSPA (EIPSP-A) was -70.2 +/- 0.9 mV (n = 32) and that of a more slowly developing hyperpolarizing response (IPSPB) was -91.4 +/- 1.3 mV (n = 28). 3. An examination of the temporal relationships between excitatory postsynaptic potentials (EPSPs) and IPSPAs in different cells suggested that, despite partial overlap of these responses, EPSPs had little influence on the measured values of EIPSP-A. 4. Application of 20 mM trimethylamine (TriMA), a membrane-permeant weak base which is expected to produce a rise in pHi (and hence in intracellular HCO3-), induced a reversible positive shift in EIPSP-A of up to +9.0 mV (mean + 4.2 mV) at an extracellular pH (pHo) of 7.4. In some experiments, the shift in reversal potential was associated with a change in the polarity of IPSPA from hyperpolarizing to depolarizing. 5. Application of 20 mM lactate (a membrane-permeant weak acid which is expected to produce a fall in pHi and hence in intracellular HCO3-) at pHo 7.0 produced a hyperpolarizing shift in EIPS-A of up to -7.5 mV (mean -5.6 mV). In some experiments, exposure to lactate changed the polarity of IPSPA from depolarizing to hyperpolarizing. 6. Changes in pHo from 7.4 to 7.0 reduced the effect of TriMA and augmented that of lactate on EIPSP-A, as could be expected on the basis of the pHo-dependent change in the fraction of membrane permeable non-charged weak base or acid. 7. Under control conditions, a change in pHo from 7.4 to 7.0 produced a slight positive shift (< +2 mV) in EIPSP-A. In the presence of TriMA, a similar change in pHo gave rise to a negative shift (-1.8 to -2.7 mV). 8. The results obtained indicate that HCO3- ions contribute significantly to the IPSPA, thereby making EIPSP-A more positive than the Cl- equilibrium potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Synaptic inhibition in primary and secondary chronic epileptic foci induced by intrahippocampal tetanus toxin in the rat.

1. Injecting twelve mouse minimum lethal doses of tetanus toxin into one hippocampus of a rat leads to the development of chronic epileptic foci in both hippocampi. These generate intermittent epileptic discharges for 6-8 weeks. Here we compare GABAergic inhibition, 10-18 days after injection, in slices prepared from the injected and contralateral hippocampi (respectively the primary and the secondary or 'mirror' foci), using both neurochemical and electrophysiological methods. 2. Epileptic activity was recorded from slices of both hippocampi from all tetanus toxin-injected rats. Evoked epileptic discharges were similar on the two sides, but spontaneous epileptic discharges were more common contralaterally. 3. Ca(2+)-dependent, K(+)-stimulated (synaptic) release of radiolabelled GABA was depressed in slices from the injected hippocampus, compared with vehicle-injected controls. In contrast, slices from the contralateral hippocampus had normal levels of Ca(2+)-dependent, K(+)-stimulated GABA release, even though adjacent slices were epileptogenic. 4. Intracellular recordings revealed that both fast and slow stimulus-evoked inhibitory postsynaptic potentials (IPSPs) were abolished in CA3 pyramidal cells in the primary focus. In the secondary focus, however, fast IPSPs were seen in seven of twenty-five cells, and slow IPSPs were seen in all cells if the stimulus was strong enough. 5. Monosynaptic IPSPs were isolated pharmacologically by blocking glutamatergic excitatory postsynaptic potentials (EPSPs) with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D(-)-2-amino-5-phosphopentanoic acid (AP-5). No monosynaptic IPSPs were uncovered in cells from the primary focus at any stimulus strength. Monosynaptic IPSPs were evoked in all cells from both the secondary focus and control slices. The estimated conductances of monosynaptic fast IPSPs were similar in cells from the secondary focus and from the controls, although the former required twice the stimulus strength. 6. Slow IPSPs were found in the secondary focus and in controls, but not in the primary focus. They were sensitive to 3-amino-2-(4-chlorophenyl)-2-hydroxy-propylsulphonic acid (2-OH saclofen). The estimated conductances of slow IPSPs evoked by weak stimuli in the secondary focus were much smaller than in the controls. However, stimuli that could trigger epileptic discharges in the secondary focus, evoked 2-OH saclofen-sensitive slow IPSPs with estimated conductances approaching the controls. This marked increase in the slow IPSP did not occur when EPSPs, and epileptic bursts, were blocked with CNQX and AP-5, suggesting that a strong barrage of excitation is needed to generate full-sized slow IPSPs in the secondary focus.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1993

GABAB receptors modulate glycinergic inhibition and spike threshold in Xenopus embryo spinal neurones.

1. The actions of GABAB receptors in the generation of the neuronal pattern underlying swimming in the Xenopus embryo have been investigated using the agonist baclofen. 2. Baclofen (10-100 microM) greatly reduced the length of swimming episodes and ventral root spike amplitude in a reversible manner. These effects were blocked by CGP 35348 (200-300 microm) and hydroxysaclofen (200-300 microM). 3. Baclofen (10-100 microM) reduced the amplitude of glycinergic IPSPs in motoneurones during fictive swimming. 4. Strychnine-sensitive spontaneous miniature inhibitory postsynaptic potentials (mIPSPs) were recorded from motoneurones. While baclofen (10-100 microM) had no effect on the amplitude of the mIPSPs it greatly decreased their frequency of occurrence. 5. GABAB receptors may therefore be present on the terminals of commissural interneurones, the only glycinergic neurones in the Xenopus embryo's nervous system, and act to reduce neurotransmitter release. 6. Baclofen reduced the reliability of action potential firing in motoneurones during fictive swimming without an apparent effect on excitation. 7. Baclofen increased the threshold to action potential firing in response to the injection of depolarizing current in motoneurones. 8. The current-voltage relationships of motoneurones were investigated. Baclofen (10-100 microM) did not change the resting membrane potential, slope conductance or the membrane rectification.

Action Potentials↗

PubMed1994

Synchronization of inhibitory neurones in the guinea-pig hippocampus in vitro.

1. Intracellular recordings were obtained from pyramidal, granule and hilar cells in transverse slices of guinea-pig hippocampus to examine synaptic interactions between GABAergic neurones. 2. In the presence of the convulsant compound 4-aminopyridine (4-AP), after fast excitatory amino acid (EAA) neurotransmission was blocked pharmacologically, large amplitude inhibitory postsynaptic potentials (IPSPs) occurred rhythmically (every 4-8 s) and synchronously in all principal cell populations (triphasic synchronized IPSPs). In the presence of the GABAA receptor blocker picrotoxin (PTX), a large amplitude IPSP continued to occur spontaneously in all principal cells simultaneously (monophasic synchronized IPSP). 3. Burst firing occurred simultaneously in a group of hilar neurones (synchronized bursting neurones) coincident with triphasic synchronized IPSPs in principal cells. After PTX was added, the bursts and the underlying depolarizing synaptic potentials were completely suppressed in some of the synchronized bursting neurones (type I hilar neurones), while others (type II hilar neurones) continued to fire in bursts coincident with monophasic synchronized IPSPs in principal cells. Intense hyperpolarization blocked burst firing and revealed underlying attenuated spikes of less than 10 mV, but did not uncover any underlying depolarizing synaptic potentials. 4. In type II hilar neurones, during sufficient hyperpolarization, spontaneous activity consisted of attenuated spikes. With depolarization, the small spikes began to trigger full size action potentials. These data suggest the presence of electrotonically remote spike initiation sites. 5. The morphology of synchronized bursting neurones was revealed by intracellular injection of the fluorescent dye Lucifer Yellow. Attempts to inject dye into one type II hilar neurone often resulted in the labelling of two to four cells (dye coupling). Dye coupling was not observed in type I hilar neurones. 6. These findings indicate that excitatory interactions synchronizing the firing of GABAergic neurones can occur in the absence of fast EAA neurotransmission. GABAergic neurones can become synchronized via their recurrent collaterals through the depolarizing action of synaptically activated GABAA receptors. In addition, a subpopulation of GABAergic neurones can become synchronized by a mechanism probably involving electrotonic coupling.

4-Aminopyridine↗

PubMed1995

Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro.

1. The cellular basis for generation of spindle waves and a slower synchronized oscillation resembling absence seizures was investigated with extracellular and intracellular recording techniques in slices of ferret dorsal lateral geniculate nucleus (LGNd) maintained in vitro. 2. Intracellular recording from LGNd relay cells in vitro revealed that spindle waves occurred once every 3-30 s and were associated with barrages of inhibitory postsynaptic potentials (IPSPs) occurring at a frequency of 6-10 Hz. These IPSPs resulted in the generation of rebound low threshold Ca2+ spikes at 2-4 Hz, owing to the intrinsic propensity of LGNd relay cells to generate oscillatory burst firing in this frequency range. These rebound bursts of action potentials were highly synchronized with local multiunit and single unit activity. 3. The spindle wave-associated IPSPs in LGNd relay cells exhibited a mean reversal potential of -86 mV. This reversal potential was shifted to more depolarized membrane potentials with the intracellular injection of Cl- through the use of KCl-filled microelectrodes. Simultaneous recording from the perigeniculate nucleus (PGN) and LGNd revealed the IPSPs to be synchronous with the occurrence of burst firing in the PGN. Excitation of PGN neurons with local electrical stimulation after pharmacological block of excitatory amino acid transmission resulted in bicuculline-sensitive IPSPs in relay neurons similar in amplitude and time course to those occurring during spindle waves. 4. Application of (-)-bicuculline methiodide resulted in the abolition of spindle wave-associated IPSPs or in the slowing of the rate of rise, an increase in amplitude and a prolongation of these IPSPs; this resulted in a synchronized 2-4 Hz oscillation, in which each relay cell strongly burst on nearly every cycle, thus forming a paroxysmal event. Bath application of the GABAB receptor antagonist 2-OH-saclofen blocked these slowed oscillations, indicating that they are mediated by the activation of GABAB receptors. In contrast, pharmacological antagonism of GABAB receptors did not block the generation of normal spindle waves. 5. These and other results indicate that spindle waves are generated in the ferret LGNd in vitro as a network phenomenon occurring through an interaction between the relay cells of the LGNd and the GABAergic neurons of the PGN. We propose that burst firing in PGN cells hyperpolarizes relay neurons through activation of GABAA receptors. These IPSPs result in rebound burst firing in LGNd cells, which then excite PGN neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

Regulation of EPSPs by the synaptic activation of GABAB autoreceptors in rat hippocampus.

1. Intracellular recording was used to study the influence of GABAB autoreceptor-mediated regulation of monosynaptic GABAA and GABAB receptor-mediated hyperpolarizing inhibitory postsynaptic potentials (IPSPAs and IPSPBs, respectively) on alpha-amino-3-hydroxy-5-methyl -4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potentials (EPSPAs and EPSPNs, respectively) in the CA1 region of rat hippocampal slices. To achieve this, synaptic potential were evoked monosynaptically by near stimulation following blockade of either EPSPNs, by the NMDA receptor antagonist (R)-2-amino-5-phosphonopentanoate (AP5; 0.05 mM), or EPSPAs, by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.01 mM). 2. Paired-pulse stimulation at 3-50 Hz caused an increase in the duration (paired-pulse widening) of EPSPAs, which paralleled the time course of paired-pulse depression of monosynaptic IPSCs, and a potentiation of the amplitude (paired-pulse potentiation) of EPSPAs, which did not. Paired-pulse stimulation also caused frequency-dependent changes in EPSPNs. At frequencies > 40 Hz it produced paired-pulse depression of EPSPNs, along with marked summation of IPSPS, and at frequencies < 40 Hz it caused paired-pulsed enlargement of EPSPNs, concomitant with a reduction in IPSPS. 3. Paired-pulse potentiation of EPSPAs at 50 Hz was enhanced by picrotoxin (0.1 mM) but was not significantly affected by 3-amino-propyl(diethoxymethyl)phosphinic acid (CGP 35348; 1 mM). Paired-pulse depression of EPSPNs at 50 Hz was converted to paired-pulse enlargement by picrotoxin but was unaffected by CGP 35348. These effects can be explained by block of IPSPAs by picrotoxin. 4. Paired-pulsed widening of EPSPAs at 5 Hz was occluded by picrotoxin and abolished by CGP 35348. Similarly, paired-pulsed enlargement of EPSPNs at 5 Hz was occluded, and in some cases converted to paired-pulse depression, by picrotoxin. The effects of CGP 35348 were more complex in that this antagonist reduced paired-pulse enlargement of EPSPNs in control medium whereas it eliminated paired-pulsed depression of EPSPNs in the presence of picrotoxin, effects consistent with its block of GABAB autoreceptors and IPSPBS, respectively. 5. 'Priming' using a 'priming stimulation protocol' (a single 'priming stimulus' followed at 1-50 Hz ('priming frequency') by a 'primed burst' of four shocks at 20-100 Hz ('burst frequency')) caused an increase in both 'primed' EPSPAs and EPSPNs compared with 'unprimed' EPSPAs and EPSPNs. This effect was optimal when the respective priming and burst frequencies were 5 and 100 Hz. 6. In the presence of either picrotoxin or CGP 35348 the primed EPSPAs and EPSPNs resembled unprimed EPSPAs and EPSPNs, respectively. This was because picrotoxin occluded whereas CGP 35348 blocked the effect of priming on EPSPS. 7. CGP 35348 had only modest effects on EPSPAs but enhanced EPSPNs evoked by a tetanus (20 stimuli at 100 Hz), in either the presence or absence of picrotoxin. In the absence of picrotoxin, CGP 35348 also promoted depolarization by enhancing a depolarizing GABAA receptor-mediated component (IPSPD). These effects can all be attributed to block of IPSPBS by CGP 35348. 8. CGP 35348 blocked the induction of long-term potentiation (LTP) of extracellularly recorded field EPSPs elicited by a priming stimulation protocol in control medium but was ineffective in the presence of picrotoxin. CGP 35348 was also ineffective at preventing tetanus-induced LTP (100 Hz, 1 s) in both the absence and presence of picrotoxin. 9. These data demonstrate the complex regulation of AMPA and NMDA receptor-mediated EPSPs during various patterns of synaptic activation caused by the dynamic changes in GABA-mediated synaptic inhibition, which are orchestrated by GABAA autoreceptors in a frequency-dependent

Animals↗

PubMed1996

GABA and glutamate mediate rapid neurotransmission from suprachiasmatic nucleus to hypothalamic paraventricular nucleus in rat.

1. Intracellular sharp electrode and whole-cell patch-clamp recording from characterized paraventricular nucleus (PVN) neurones in rat hypothalamic slices were used to study the synaptic mechanism and associated neurotransmitters that mediate their response to suprachiasmatic nucleus (SCN) stimulation. 2. Electrical stimulation restricted to SCN evoked short-latency inhibitory postsynaptic potentials (IPSPs) or combinations of IPSPs and excitatory postsynaptic potentials (EPSPs) in all (n = 59) PVN neurones tested. Type I neurones (n = 18) were magnocellular and a majority (13/18) demonstrated monosynaptic IPSPs that reversed polarity at the chloride equilibrium potential and were sensitive to bicuculline. 3. Type II (n = 10) and III parvocellular (n = 13), and unclassifiable neurones (n = 18) displayed combinations of IPSPs and EPSPs following similar stimuli applied to SCN. IPSP blockade with bicuculline uncovered SCN-evoked monosynaptic dual-component EPSPs that were sensitive to N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. In addition, chemical microstimulation within SCN was associated with transient increases in spontaneous EPSPs recorded from these PVN neurones. 4. These data imply that the amino acids GABA and glutamate are important mediators of fast monosynaptic transmission from SCN to defined neurones in PVN, and are candidates for conveying circadian rhythmicity to PVN regulation of neuroendocrine and autonomic processes.

Animals↗