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PubMed1983

Direct projections from vestibular nuclei to facial nucleus in cats.

Postsynaptic potentials were recorded from motoneurons in the facial nucleus in response to stimulation of the vestibular and trigeminal nerves. The motoneurons were identified by antidromic activation from their peripheral axons. Disynaptic excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) and mixed EPSP/IPSPs were recorded in response to vestibular nerve stimulation, ranging in latency from 0.9 to 2.1 ms, with most at 1.5 ms. Activity in secondary vestibular axons recorded within the facial nucleus occurred at a latency of 0.7-1.1 ms. The amplitudes of the vestibular postsynaptic potentials were small, generally less than a millivolt, but double shocks produced marked summation. The average time to peak of ipsilateral vestibular EPSPs, 1.1 ms, was faster than that of either ipsilateral IPSPs, 1.6 ms, or contralateral EPSPs, 1.4 ms. The double-spiked vestibular activity was detectable in double-peaked PSPs. Disynaptic EPSPs, ranging in latency from 2.0 to 3.0 ms, were recorded in response to trigeminal nerve stimulation. The average time to peak was 1.3 ms. The multiple-spiked activity of the trigeminal neurons was detectable in multipeaked EPSPs. Inhibitory ipsilateral effects (Vi IPSPs) were recorded twice as often as excitatory ipsilateral effects (Vi EPSPs), being found in 29% versus 15% of the motoneurons. Contralateral effects were found in 13% of the motoneurons studied, and almost all were excitatory. Analysis of synaptic potential shapes suggested that the excitatory and inhibitory vestibular synapses probably contact distal dendrites preferentially, with the excitatory connections being somewhat closer to the soma. The trigeminal inputs probably contact the facial motoneurons more extensively near the soma. Horseradish peroxidase was injected into the facial nucleus, and retrograde uptake by vestibular neurons was studied. The majority of filled vestibular neurons was ipsilateral to the injection site, especially in the medial vestibular nucleus, ventral y group, and supravestibular nucleus. On the contralateral side, filled vestibular cells were found almost exclusively in the medial nucleus. Filled cells were also noted in the trigeminal nucleus, predominantly ipsilaterally at all rostrocaudal levels. We have demonstrated monosynaptic projections to facial motoneurons from both vestibular and trigeminal nuclei. The trigeminal input is likely to be involved in facial reflexes, especially blinking and grimacing. The afferent vestibular population overlaps that going to the oculomotor and cervical motoneurons; these projections may be collaterals of single vestibular neurons.4+.

Animals↗

PubMed1992

Local synaptic circuits and epileptiform activity in slices of neocortex from children with intractable epilepsy.

1. Single and dual intracellular recordings were performed in neocortical slices obtained from tissue samples surgically removed from children (8 mo to 15 yr) for the treatment of intractable epilepsy. Electrical stimulation and glutamate microapplication were used to study local synaptic inputs to pyramidal cells. 2. In recordings with potassium-acetate electrodes, activation of presynaptic neocortical neurons with glutamate microdrops did not elicit a clear increase in postsynaptic potentials (PSPs) but did suppress current-evoked repetitive spike firing in recorded neurons. Bicuculline (10 microM) blocked this effect, suggesting it was caused by the activation of presynaptic gamma-aminobutyric acid (GABA) cells. In recordings with KCl electrodes, glutamate microdrops elicited an increase in the frequency and amplitude of depolarizing PSPs. Bicuculline (5-10 microM) blocked the glutamate-evoked PSPs, suggesting they were reversed GABAA-receptor-mediated inhibitory postsynaptic potentials (IPSPs). In one cell recorded with a KCl electrode (total n = 8), current-evoked spike trains elicited afterdischarges of reversed IPSPs, thus revealing a recurrent inhibitory circuit. Therefore local inhibitory synaptic circuits were robust and could be observed in tissue from patients as young as 11 mo. 3. In addition to short-latency (10-25 ms), monosynaptic excitatory postsynaptic potentials (EPSPs), electrical stimulation at low intensities sometimes elicited delayed EPSPs (20-60 ms). When GABAA-receptor-mediated synaptic inhibition was partially reduced in bicuculline (5-10 microM), electrical stimulation evoked large EPSPs at long and variable latencies (100-300 ms). Glutamate microapplication caused an increase in the frequency and amplitude of EPSPs; preliminary results suggest that glutamate microdrops were less likely to evoke EPSPs in tissue from younger patients (8-12 mo) than in slices from patients greater than 4 yr. Evidence for local excitatory synaptic circuits was thus found when synaptic inhibition was partially reduced. 4. After further reduction of inhibition in bicuculline (5-50 microM), electrical stimulation elicited epileptiform bursts. In pairs of simultaneously recorded neurons, bursts were generated synchronously from long-latency EPSPs (100-300 ms) in slices from patients as young as 8 mo. Reflected EPSPs at very long and variable latencies (500-1,100 ms) and repetitive epileptiform bursts could be evoked synchronously in pairs of cells. Glutamate activation of local presynaptic neurons elicited robust epileptiform events in recorded cells. This was seen in slices from patients as young as 16 mo. 5. These data provide physiological evidence for the presence of local inhibitory and excitatory synaptic circuits in human neocortex at least as early as 11 and 8 mo, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1996

Monosynaptic input from cutaneous sensory afferents to fin motoneurons in lamprey.

The sensory control of lamprey dorsal fin motoneurons was studied by using paired intracellular recordings combined with a morphological analysis. Dorsal cells innervating the skin of the dorsal fin and fin motoneurons were retrogradely labeled by injecting fluoresceincoupled dextran amines into the dorsal fin. Labeled motoneurons and dorsal cells showed close appositions, suggesting that the dorsal cells innervating the fin region make monosynaptic connections with fin motoneurons. By using conventional electrophysiological criteria, monosynaptic excitatory connections were found between fin dorsal cells and fin motoneurons. In addition, Lucifer yellow injection followed by confocal three-dimensional (3-D) reconstructions of monosynaptically connected pairs, revealed close apposition between dorsal cell axons and the distal dendrites of fin motoneurons. Each fin motoneuron received monosynaptic excitatory input from at least four different afferents. The amplitude of the monosynaptic excitatory postsynaptic potential (EPSP)s was reduced by administration of the N-methyl-D-aspartate (NMDA) receptor antagonist DL,2 amino-5-phosphovaleric acid (APV). Sensory stimulation could also elicit di- or oligosynaptic inhibitory postsynaptic potential (IPSP)s, which were blocked by the glycine antagonist strychnine, resulting in the appearance of large monosynaptic EPSPs, which could induce action potentials.

2-Amino-5-phosphonovalerate↗

PubMed1984

Contrasting effects of neurohypophysial peptides on pyramidal and non-pyramidal neurones in the rat hippocampus.

Oxytocin and vasopressin increased the rate of firing of a class of presumed non-pyramidal neurones located in the CA1 area of rat hippocampal slices. This excitatory effect persisted in conditions of synaptic uncoupling. In contrast, pyramidal neurones were either unaffected by neurohypophysial peptides or showed one or several of the following effects: a decrease in firing rate in cells which were spontaneously active; a slight membrane hyperpolarization; and an increase in the rate of occurrence of spontaneous inhibitory postsynaptic potentials. We therefore propose that oxytocin and vasopressin excite directly a class of non-pyramidal inhibitory interneurones, whereas their observed effect on pyramidal neurones is indirect and inhibitory.

Action Potentials↗

PubMed1987

Vestibular effects in long C3-C5 propriospinal neurones.

The effects of stimulation of the vestibular nerve and of regions in and around the vestibular nuclei on long C3-C5 propriospinal neurones (PNs) were investigated with intracellular recording. Disynaptic excitatory postsynaptic potentials were evoked from the contralateral (co) or ipsilateral (i) vestibular nerve in many long PNs but mainly in crossed PNs from the co and in uncrossed from the i nerve. Disynaptic inhibitory postsynaptic potentials were evoked more rarely, mainly from the i vestibular nerve. Threshold mapping revealed an excitatory relay from the co nerve in the medial vestibular nucleus (MVN) and also that the excitatory MVN neurones projecting to the long PNs send collaterals to the abducens and interstitial nucleus of Cajal. Excitation from the i vestibular nerve was relayed in the lateral vestibular nucleus (LVN) and in the MVN. Also, non-second order LVN neurones project to the long PNs. Monosynaptic IPSPs were evoked from the i MVN and i LVN.

Brain Mapping↗

PubMed1997

Computer model of clonazepam's effect in thalamic slice.

In the thalamus, paradoxical changes in response to augmentation of inhibition can occur as a result of either cellular or network effects. Clonazepam, a GABA(A) agonist, produces a paradoxical reduction in evoked thalamocortical neuron inhibitory postsynaptic potential (IPSP) in thalamic slice. This has been hypothesized to be a result of augmentation in inhibitory to inhibitory connections. In a computer model, orthodromic simulation produced an increase in initial IPSP, a result contrary to that found experimentally. This failure was traced to the inability of orthodromic activation to produce fast enough recurrent inhibition to alter initial reticularis neuron firing. Simulated antidromic stimulation was able to reduce this initial spike train and reproduced the experimental finding.

Animals↗

PubMed1998

Synaptic depression at type B to A photoreceptor connections in Hermissenda.

We quantified synaptic depression at the type B to A photoreceptor connections of Hermissenda. Type B cell action potentials were evoked at interstimulus intervals (ISIs) of 0.3, 3 or 30 s and the resulting inhibitory postsynaptic potentials (IPSPs) were recorded in a type A cell. A progressive decline in IPSP amplitude occurred at all three ISIs. Synaptic depression was greater at shorter ISIs, as was the level of recovery 2 min after the stimulus series. The profound level of synaptic depression observed (79.0+/-3.2% at the 0.3 s ISI) implies that synaptic depression is an important control process in the neuronal circuitry that drives phototactic behavior.

Action Potentials↗

PubMed1997

Plateau potentials in cat neocortical association cells in vivo: synaptic control of dendritic excitability.

The dendrites of neocortical pyramidal cells are bombarded by myriads of synaptic inputs and express active conductances generating prominent plateau potentials. We have examined in vivo the possibility that spontaneous synaptic inputs trigger or terminate plateau potentials after blockage of K+ currents. Under barbiturate anaesthesia, pairs of cortical cells were intracellularly recorded with sharp electrodes from the cat's association cortex (areas 5-7). In one pyramidal cell, K+ channels were blocked with intracellular Cs+, while in the simultaneously impaled pyramidal cell the K+ conductances were left intact to act as a control; this second cell allowed recognition of spontaneous spindle-related synaptic activity. Depolarizing current pulses elicited single, all-or-none plateau potentials (60-70 mV, 0.1-0.4 s). Plateau potentials slowly repolarized towards a break point of fast repolarization around -20 mV. Thalamic-evoked inhibitory postsynaptic potentials consistently shut off the plateaus. Synchronized spontaneous activity, as occurring during thalamic-generated spindle oscillations, either triggered or blocked the plateaus. These results suggest that spontaneously occurring synaptic activation during synchronized oscillatory states, such as those that occur during sleep spindles in vivo, may exert a strong control over the dendritic excitability in neocortical pyramidal cells.

Action Potentials↗

PubMed1988

Enkephalin hyperpolarizes interneurones in the rat hippocampus.

1. Intracellular recordings were made from pyramidal cells and from electrophysiologically identified interneurones in the CA1 region of the hippocampal slice preparation from the rat. 2. Enkephalin blocked the hyperpolarization of pyramidal cells evoked by application of glutamate to synaptically coupled inhibitory interneurones. 3. Enkephalin hyperpolarized interneurones, most probably by increasing potassium conductance; this action was blocked by the opiate antagonist, naloxone. 4. Activation of gamma-aminobutyric acid(B) receptors with baclofen in interneurones produced a similar hyperpolarization that was resistant to naloxone. 5. In addition to hyperpolarizing interneurones, enkephalin blocked the inhibitory postsynaptic potential recorded in these cells. 6. These results suggest that opiate receptors are selectively localized on inhibitory interneurones in the hippocampus and are coupled to potassium channels. Activation of these receptors causes a disinhibition of both pyramidal cells and inhibitory interneurones.

Action Potentials↗

PubMed2005

Heterogeneous chloride homeostasis and GABA responses in the median preoptic nucleus of the rat.

The median preoptic nucleus (MnPO) is an integrative structure of the hypothalamus receiving periphery-derived information pertinent to hydromineral and cardiovascular homeostasis. In this context, excitability of MnPO neurones is controlled by fast GABAergic, glutamatergic and angiotensinergic projection from the subfornical organ (SFO). Taking advantage of a brain slice preparation preserving synaptic connection between the SFO and the MnPO, and appropriate bicarbonate-free artificial cerebrospinal fluid (CSF), we investigated a possible implication of an active outward Cl- transport in regulating efficacy of the GABA(A) receptor-mediated inhibitory response at the SFO-MnPO synapse. When somata of the MnPO neurones was loaded with 18 mm chloride, stimulation of the SFO evoked outward inhibitory postsynaptic currents (IPSCs) in 81% of the MnPO neurones held at -60 mV. Accordingly, E(IPSC) was found 25 mV hyperpolarized from the theoretical value calculated from the Nernst equation, indicating that IPSC polarity and amplitude were driven by an active Cl- extrusion system in these neurones. E(IPSC) estimated with gramicidin-based perforated-patch recordings amounted -89.2 +/- 4.3 mV. Furosemide (100 microm), a pharmacological compound known to block the activity of the neurone-specific K(+)-Cl- cotransporter, KCC2, reversed IPSC polarity and shifted E(IPSC) towards its theoretical value. Presence of the KCC2 protein in the MnPO was further detected with immunohistochemistry, revealing a dense network of KCC2-positive intermingled fibres. In the presence of a GABA(B) receptor antagonist, high-frequency stimulation (5 Hz) of the SFO evoked a train of IPSCs or inhibitory postsynaptic potentials (IPSPs), whose amplitude was maintained throughout the sustained stimulation. Contrastingly, similar 5 Hz stimulation carried out in the presence of furosemide (50 microm) evoked IPSCs/IPSPs, whose amplitude collapsed during the high-frequency stimulation. Similar reduction in inhibitory neurotransmission was also observed in MnPO neurones lacking the functional Cl- extrusion mechanism. We conclude that a majority of MnPO neurones were characterized by a functional Cl- transporter that ensured an efficient activity-dependent Cl- transport rate, allowing sustained synaptic inhibition of these neurones. Pharmacological and anatomical data strongly suggested the involvement of KCC2, as an essential postsynaptic determinant of the inhibitory neurotransmission afferent to the MnPO, a key-structure in the physiology of the hydromineral and cardiovascular homeostasis.

Animals↗

PubMed1987

Intracellular recordings in pericruciate neurons during spike and wave discharges of feline generalized penicillin epilepsy.

Concurrent EEG and intracellular recordings from pericruciate neurons of cats obtained before and after i.m. injection of penicillin inducing the syndrome of feline generalized penicillin epilepsy (FGPE) characterized by spike and wave (SW) discharge in the EEG, display large excitatory postsynaptic potentials (EPSPs) at the time of the EEG 'spike' which alternate with hyperpolarizing potentials occurring in coincidence with the EEG 'wave' component of the SW complex. The large EPSPs trigger discharges of single or multiple high-frequency action potentials which do not show a progressive decrement in amplitude nor an appreciable increase in duration. These bursts thus differ in some respects from typical paroxysmal depolarization shifts. The hyperpolarizing potentials show an early phase which is reversed by intracellular Cl- injection or diffusion and thus behaves like a classical inhibitory postsynaptic potential (IPSP). The late phase is unaffected by Cl-. Hyperpolarizing potentials of pericruciate neurons induced by antidromic activation of the cerebral peduncle (CP) or by direct cortical stimulation are not altered after i.m. injections of penicillin at doses sufficient to induce generalized SW discharge. The early phase of hyperpolarization both before and after i.m. penicillin is reversed by intracellular Cl- injection or diffusion, the late phase remains unchanged. The early phase thus represents a classical IPSP, which does not appear to be affected by the low brain penicillin concentrations sufficient to induce generalized SW discharge. It is concluded that this form of epileptic discharge cannot be attributed to blockage of phasic (presumably somatic) postsynaptic inhibition by penicillin. These results indicate that to regard all forms of epileptic discharge as the consequence of a blockage of gamma-aminobutyric acid-mediated phasic postsynaptic inhibition acting on the soma represents an unduly restrictive view of epileptogenesis.

Animals↗

PubMed1993

Synaptic activation in guinea-pig dentate area: dependence on the stimulation site.

A negative-going and a positive-going field potential were evoked in the granule cell layer by electrical stimulation of a region near the cell layer (commissural/associational fibres, cf) and of the lateral perforant path (perforant-path fibres, pp). The cf-evoked field potential was more strongly reduced by (-)baclofen (2-5 mumol l-1) and carbachol (2-5 mumol l-1) than was the pp-evoked field potential. By simultaneous intra- and extracellular recordings, the elements activated from the two stimulation sites were determined. Stimulation of cf-fibres elicited concurrently excitatory and inhibitory postsynaptic potentials, but inhibition predominated. pp stimulation elicited excitation followed by inhibition, and excitation predominated. Responses evoked from both stimulation sites were affected by antagonists for glutamatergic excitation. Inhibition blockade revealed that excitation elicited from the cf-stimulation site was largely shunted by inhibition. Presumed inhibitory neurons in the dentate hilus were driven at latencies consistent with the latencies at which inhibition was elicited in granule cells from the two stimulation sites. We conclude that the sequence of synaptic events produced by extracellular stimulation can vary substantially by slightly differing electrode placements. However, it is difficult to decide, simply on the basis of an extracellular field potential, what elements have been activated.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Synaptic inhibition of cat phrenic motoneurons by internal intercostal nerve stimulation.

Intracellular recordings from 65 phrenic motoneurons (PMNs) in the C5 segment and recordings of C5 phrenic nerve activity were made in 27 pentobarbitone-anesthetized, paralyzed, and artificially ventilated adult cats. Inhibition of phrenic nerve activity and PMN membrane potential hyperpolarization (48/55 PMNs tested) was seen after stimulation of the internal intercostal nerve (IIN) at a mean latency to onset of 10.3 +/- 2.7 ms. Reversal of IIN-evoked hyperpolarization (n = 14) by injection of negative current or diffusion of chloride ions occurred in six cases, and the hyperpolarization was reduced in seven others. Stimulation of the IIN thus activates chloride-dependent inhibitory synaptic inputs to most PMNs. The inhibitory phrenic nerve response to IIN stimulation was reduced by ipsilateral transection of the lateral white matter at the C3 level and was converted to an excitatory response by complete ipsilateral cord hemisection at the same level. After complete ipsilateral hemisection of the spinal cord at C3 level, stimulation of the IIN evoked both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in PMNs (n = 10). It was concluded that IIN stimulation can evoke both excitatory and inhibitory responses in PMNs using purely spinal circuitry, but that excitatory responses are normally suppressed by a descending pathway in intact animals. Fifteen PMNs were tested for possible presynaptic convergence of inputs in these reflex pathways, using test and conditioning stimuli. Significant enhancement (>20%) of IPSPs were seen in seven of eight IIN-evoked responses using pericruciate sensorimotor cortex (SMC) conditioning stimuli, but only one of five IIN-evoked responses were enhanced by superior laryngeal nerve (SLN) conditioning stimuli. The IIN-evoked IPSP was enhanced in one of two motoneurons by stimulation of the contralateral phrenic nerve. It was concluded that presynaptic interneurons were shared by the IIN and SMC pathways, but uncommonly by other pathways. These results indicate that PMNs receive inhibitory synaptic inputs from ascending thoracocervical pathways and from spinal interneurons. These inhibitory reflex pathways activated by afferent inputs from the chest wall may play a significant role in the control of PMN discharge, in parallel with disfacilitation following reduced activity in bulbospinal neurons projecting to PMNs.

Animals↗

PubMed2002

Properties of primary sensory (lemniscal) synapses in the ventrobasal thalamus and the relay of high-frequency sensory inputs.

The main role of the thalamus is to relay sensory inputs to the neocortex. In the primary somatosensory thalamus (ventrobasal thalamus), sensory inputs deliver tactile information through the medial lemniscus tract. The transmission of sensory information through this pathway is affected by behavioral state. For instance, the relay of high-frequency somatosensory inputs through the thalamus is suppressed during anesthesia or quiescent states but allowed during behaviorally activated states. This change may be due to the effects of modulators on the efficacy of lemniscal synapses. Here I show that lemniscal synapses of adult rodents studied in vitro produce large amplitude-highly secure unitary excitatory postsynaptic potentials (EPSPs), which depress in response to repetitive stimulation at frequencies >2 Hz. Acetylcholine and norepinephrine, which are important thalamic modulators, have no effect on the efficacy of lemniscal EPSPs but reduce evoked inhibitory postsynaptic potentials and corticothalamic EPSPs. Although acetylcholine and norepinephrine do not affect lemniscal synapses, the postsynaptic depolarization they produce on thalamocortical neurons serves to warrant the relay of lemniscal inputs at high-frequency rates by bringing the depressed lemniscal EPSPs close to firing threshold. In conclusion, acetylcholine and norepinephrine released during activated states selectively enhance sensory transmission through the lemniscal pathway by depolarizing thalamocortical neurons and simultaneously depressing the other afferent pathways.

Acetylcholine↗

PubMed1997

Connections between otolith receptors and neck motoneurons.

Intracellular recordings from ipsilateral and contralateral neck extensor and flexor motoneurons were studied to determine the connections between the utricular nerve and neck motoneurons and between saccular nerves and neck motoneurons in cats. Stimulating electrodes were placed within the left utricular nerve or saccular nerve. Electrical stimulation of the utricular nerve evoked excitatory postsynaptic potentials (EPSPs) with disynaptic latency in almost all ipsilateral extensor motoneurons and disynaptic EPSPs in all ipsilateral flexor motoneurons. In contralateral extensor and flexor motoneurons, the initial response to utricular stimulation was usually inhibitory postsynaptic potentials (IPSPs) with trisynaptic linkage. Thus, the utriculo-neck connectivities essentially differentiated between the left and right side. In response to stimulation of the saccular nerve, the initial response in bilateral extensor motoneurons ws EPSPs. Ipsilateral projections were always disynaptic; contralateral projections could be di- or trisynaptic. IPSPs were evoked in almost all bilateral flexor motoneurons with di- or trisynaptic latencies. The sacculo-neck motoneuron relationship thus has a qualitatively, bilaterally symmetric organization with regard to flexors and extensors.

Animals↗

PubMed1997

Pre- and postsynaptic modulation of spinal GABAergic neurotransmission by the neurosteroid, 5 beta-pregnan-3 alpha-ol-20-one.

The neuroactive steroid 5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha) modulates GABAA receptor function by potentiating postsynaptic GABA currents. While much is now known about the postsynaptic action of neurosteroids, far less is known about how they affect neurotransmission. We have investigated the synaptic actions of 5 beta 3 alpha in a simple vertebrate model, the embryo of the clawed toad, Xenopus laevis, in which a known GABAergic pathway, activated by the rostral cement gland, terminates swimming when the animal contacts an obstruction. Cement gland stimulation evokes bicuculline-sensitive inhibitory postsynaptic potentials (IPSPs) in motorneurones that terminate swimming and which are greatly enhanced by the presence of (1-5 microM) 5 beta 3 alpha. In the presence of TTX, depolarising inhibitory potentials are recorded with KCl-filled microelectrodes reflecting the spontaneous release of transmitter. The majority are glycinergic with durations of 20-80 ms and are blocked by strychnine while the remainder are GABAergic with durations of 90-200 ms and are abolished by bicuculline. We show here that, in the presence of 5 beta 3 alpha, the spontaneous GABA IPSPs lengthen dramatically in some cases to over 500 ms, but the glycine potentials are unaffected. The steroid has no other detectable postsynaptic effects in that the range of amplitudes of GABA potentials is unaffected and there is no change in the resting membrane potential. However, 5 beta 3 alpha also caused a marked increase in the rate of occurrence of spontaneous GABA potentials. This suggests a novel presynaptic site of action in which the steroid enhances the probability of vesicular GABA release from GABA terminals.

Anesthetics↗

PubMed1997

Differential effects of a benzodiazepine on synaptic transmissions in rat hippocampal neurons in vitro.

The effects of midazolam, one of the most popular benzodiazepines, on synaptic transmissions were compared with intracellular recordings between CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices. First, we studied the effects of midazolam on orthodromically evoked spikes, membrane properties and synaptic potentials. Secondly, the effects of a GABA(A) receptor agonist, muscimol, were examined on membrane properties to determine whether or not the densities of GABA(A) receptors are different between CA1-PCs and DG-GCs. Midazolam (75 microM) markedly depressed orthodromically evoked spikes in CA1-PCs, compared with those in DG-GCs. A GABA(A) receptor antagonist, bicuculline (10 microM), almost completely antagonized the depressant effects of midazolam on spike generation in CA1-PCs, whereas it had little effect on midazolam in dentate gyrus granule cells. Midazolam produced either depolarizing or hyperpolarizing effects on resting membrane potentials (Vm) with an input resistance decrease in CA1-PCs, whereas it produced depolarized Vm in DG-GCs. Midazolam significantly increased the amplitude of monosynaptic inhibitory postsynaptic potentials in CA1-PCs, whereas midazolam slightly decreased these in DG-GCs. Midazolam significantly decreased the amplitude of excitatory postsynaptic potentials both in CA1-PCs and DG-GCs. Muscimol (100 microM) produced either depolarizing or hyperpolarizing effects on Vm with an input resistance decrease in CA1-PCs, and it depolarized Vm with an input resistance decrease in DG-GCs. These results demonstrate that midazolam has differential effects on excitatory and inhibitory synaptic transmissions in hippocampal neurons. The mechanism of this difference could be partly due to the different types of GABA(A) receptors between CA1-PCs and DG-GCs.

2-Amino-5-phosphonovalerate↗

PubMed1995

Physiology and pharmacology of unitary synaptic connections between pairs of cells in areas CA3 and CA1 of rat hippocampal slice cultures.

1. Paired intracellular recordings were made in rat hippocampal slice cultures, with the use of either sharp microelectrodes or the whole cell configuration of the patch-clamp technique. Unitary synaptic connections were studied between pyramidal and nonpyramidal cells within and between areas CA1 and CA3. 2. Monosynaptic excitatory synaptic responses between CA3 pyramidal neurons were found in 56% of cell pairs (n = 91, 28 postsynaptic cells). Monosynaptic connections from a CA3 cell to a CA1 cell were observed in 76% of cell pairs (n = 125, 26 postsynaptic cells), but from CA1 to CA3 neurons in only 8% of cell pairs (n = 13, 13 postsynaptic cells). Monosynaptic excitatory connections were found in only 16% of CA1/CA1 cell pairs (n = 25, 10 postsynaptic cells). 3. Disynaptic inhibition was commonly observed between CA3 cell pairs (43%), but rarely found between CA3-CA1 pyramidal cell pairs (2%). In 50% of CA3 pyramidal cell pairs, synchronous inhibitory postsynaptic potentials (IPSPs) in both cells could be triggered by an action potential in one pyramidal cell. Reciprocal monosynaptic connections were found between 75% of interneuron and pyramidal cell pairs within area CA3. 4. The latency of monosynaptic CA3- to CA1-cell responses was significantly longer than for responses between two CA3 cells. Within area CA3 the latencies for inhibitory synaptic responses between interneurons and pyramidal cells were significantly shorter than those for excitatory responses between pyramidal cells. Monosynaptic excitatory postsynaptic potentials (EPSPs) in interneurons had a significantly shorter time-to-peak than those recorded in pyramidal neurons. 5. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)- and D-2-amino-5-phosphonovalerate (AP5)-sensitive components were identified in unitary monosynaptic EPSPs in CA3-CA3 and CA3-CA1 pyramidal cell pairs. The CNQX-sensitive component had a mean time-to-peak and duration of 6.2 +/- 0.3 (SE) ms and 61.2 +/- 2.0 ms, respectively, and an amplitude of approximately 1 mV (n = 93). The AP5-sensitive component of EPSPs was only detected when the cell was depolarized with respect to the resting potential, had a mean time-to-peak of 41 +/- 5 ms and duration of 121 +/- 11 ms (n = 6), and increased in amplitude with postsynaptic depolarization. 6. Unitary monosynaptic IPSPs between an interneuron and a pyramidal cell had a mean amplitude of approximately 1 mV and were fully blocked by gamma-aminobutyric acid-A (GABAA) receptor antagonists (n = 3). 7. Unitary inhibitory responses were found only within, but not between, areas CA3 or CA1.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗