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PubMed1990

[A comparison of statistical methods for quantal analysis in computer and physiological experiments].

Amplitude distributions of postsynaptic potentials were simulated in computer experiments on the basis of binomial statistics. Influences of the sample size (N) and noise standard deviation (Sn) on the determination of the quantal content (m) and quantal size (v) were studied. Four methods of the quantal parameter estimation were modified and used: histogram, variance, failure and combined method. Three last methods gave satisfactory estimations (within +/- 10%) at N = 500-1000 and Sn less than 2v. The histogram method was adequate at Sn less than or equal to v. Similar results were obtained at N = 50-200, when the experiment was repeated about ten times. Applicability of similar methods was confirmed by the analysis of an intracellular record of inhibitory postsynaptic potentials (N = 1333) from the sensorimotor cortex of rabbit.

Action Potentials↗

PubMed1998

Cholinergic agonist carbachol enables associative long-term potentiation in piriform cortex slices.

Pyramidal cells in piriform (olfactory) cortex receive afferent input from the olfactory bulb as well as intrinsic association input from piriform cortex and other cortical areas. These two functionally distinct inputs terminate on adjacent apical dendritic segments of the pyramidal cells located in layer Ia and layer Ib of piriform cortex. Studies with bath-applied cholinergic agonists have shown suppression of the fast component of the inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of the association fibers. It was previously demonstrated that an associative form of LTP can be induced by coactivation of the two fiber systems after blockade of the fast, gamma-aminobutyric acid-A-mediated IPSP. In this report, we demonstrate that an associative form of long-term potentiation can be induced by coactivation of afferent and intrinsic fibers in the presence of the cholinergic agonist carbachol.

Afferent Pathways↗

PubMed1997

Absence of a prevalent laminar distribution of IPSPs in association cortical neurons of cat.

Absence of a prevalent laminar distribution of IPSPs in association cortical neurons of cat. J. Neurophysiol. 78: 2742-2753, 1997. The depth distribution of inhibitory postsynaptic potentials (IPSPs) was studied in cat suprasylvian (association) cortex in vivo. Single and dual simultaneous intracellular recordings from cortical neurons were performed in the anterior part of suprasylvian gyrus (area 5). Synaptic responses were obtained by stimulating the suprasylvian cortex, 2-3 mm anterior to the recording site, as well as the thalamic lateral posterior (LP) nucleus. Neurons were recorded from layers 2 to 6 and were classified as regular spiking (RS, n = 132), intrinsically bursting (IB, n = 24), and fast spiking (FS, n = 4). Most IB cells were located in deep layers (below 0.7 mm, n = 19), but we also found some IB cells more superficially (between 0.2 and 0.5 mm, n = 5). Deeply lying corticothalamic neurons were identified by their antidromic invasion on thalamic stimulation. Neurons responded with a combination of excitatory postsynaptic potentials (EPSPs) and IPSPs to both cortical and thalamic stimulation. No consistent relation was found between cell type or cell depth and the amplitude or duration of the IPSPs. In response to thalamic stimulation, RS cells had IPSPs of 7.9 +/- 0.9 (SE) mV amplitude and 88.9 +/- 6.4 ms duration. In IB cells, IPSPs elicited by thalamic stimulation had 7.4 +/- 1.3 mV amplitude and 84.7 +/- 14.3 ms duration. The differences between the two (RS and IB) groups were not statistically significant. Compared with thalamically elicited inhibitory responses, cortical stimulation evoked IPSPs with higher amplitude (12.3 +/- 1.7 mV) and longer duration (117 +/- 17.3 ms) at all depths. Both cortically and thalamically evoked IPSPs were predominantly monophasic. Injections of Cl- fully reversed thalamically as well as cortically evoked IPSPs and revealed additional late synaptic components in response to cortical stimulation. These data show that the amount of feed forward and feedback inhibition to cat's cortical association cells is not orderly distributed to distinct layers. Thus local cortical microcircuitry goes beyond the simplified structure determined by cortical layers.

Animals↗

PubMed1990

Effects of tetrahydro-9-aminoacridine on cortical and hippocampal neurons in the rat: an in vivo and in vitro study.

The effects of tetrahydro-9-aminoacridine (THA), an anticholinesterase drug, have been studied in the rat both in vivo (cerebral cortex) and in vitro (CA1 field of the hippocampus) and compared with those of physostigmine. In the cerebral cortex THA potentiated the excitatory effect of acetylcholine in most neurons, including cortical neurons recorded from chronic unanesthetized animals. In vitro, THA (but not physostigmine) had a depolarizing, atropine- and tetrodotoxin-insensitive effect. This effect is associated with an increase in membrane resistance which suggests a direct effect of THA on hippocampal neurons. In addition THA blocked the slow inhibitory postsynaptic potential. At the same concentration THA potentiated the slow cholinergic excitatory postsynaptic potential produced by electrical stimulation of the cholinergic afferents. Its potency was, however, about 10 times lower than that of physostigmine. These results show that THA: (1) is an anticholinesterase much less potent than physostigmine; but (2) has also direct effects on central neurons, not observed with physostigmine and unrelated to its anticholinesterase activity.

Action Potentials↗

PubMed1998

Locomotor modulation of disynaptic EPSPs from the mesencephalic locomotor region in cat motoneurons.

Locomotor modulation of disynaptic EPSPs from the mesencephalic locomotor region in cat motoneurons. J. Neurophysiol. 80: 3284-3296, 1998. When low-frequency tetanization of the mesencephalic locomotor region (MLR) produce fictive locomotion in unanesthetized, decerebrate cats, each MLR stimulus produces a distinctive cord dorsum potential (CDP) and oligosynaptic excitatory postsynaptic potentials (EPSPs) in many lumbosacral motoneurons. The average segmental latency from the initial CDP wave [mean delay from stimulus: 4.3 +/- 0.9 (SD) ms] to the onset of detectable MLR EPSPs was 1.6 +/- 0.4 ms, suggesting a disynaptic segmental connection. In gastrocnemius/soleus, flexor hallucis longus, flexor digitorum longus, tibialis anterior, and posterior biceps-semitendinosus motoneurons (35/38 cells), MLR EPSPs either appeared or were enhanced during the phase of fictive stepping in which the target motoneurons were depolarized and the motor pool was active (the phase), with parallel changes between EPSP amplitudes and membrane depolarization. In contrast, MLR stimulation produced small (1/10) or no EPSPs in extensor digitorum longus (EDL) motoneurons, with no phase enhancement (4/10) or oligosynaptic inhibitory postsynaptic potentials during the phase (5/10). Eight of 10 flexor digitorum longus (FDL) cells exhibited membrane depolarization in the early flexion phase of fictive stepping, and five of these showed parallel enhancement of disynaptic MLR EPSPs during early flexion. Three cases were studied when the FDL motor pool exhibited exclusively extensor phase firing. In these cases, the disynaptic MLR EPSPs were enhanced only during the extensor phase, accompanied by membrane depolarizations. We conclude that the last-order interneurons that produce disynaptic MLR EPSPs may well participate in producing the depolarizing locomotor drive potentials (LDPs) found in hindlimb motoneurons during fictive locomotion. However, the absence of linkage between MLR EPSP enhancement and LDP depolarizations in EDL motoneurons suggests that other types of excitatory interneurons also must be involved at least in some motor pools. We compared these patterns with the modulation of disynaptic EPSPs produced in FDL cells by stimulation of the medial longitudinal fasciculus (MLF). In all seven FDL motoneurons tested, disynaptic MLF EPSPs appeared only during the extension phase, regardless of when the FDL motoneurons were active. The fact that the modulation patterns of MLR and MLF disynaptic EPSPs is different in FDL motoneurons indicates that the two pathways do not converge on common last-order interneurons to that motor pool.

Animals↗

PubMed1991

Serotonin facilitates GABAergic transmission in the CA1 region of rat hippocampus in vitro.

1. The effect of serotonin on inhibitory synaptic transmission was examined in forty-one CA1 pyramidal neurones using intracellular voltage recordings in vitro. 2. Serotonin (20-50 microM) increased the synaptic noise of most (85%) neurones loaded with chloride (n = 33). The duration of this effect was enhanced with increasing concentrations of serotonin and was fully reversible within 5 min. When serotonin was applied at short intervals (less than 10 min), fading of the response was observed. 3. The effect of serotonin on synaptic noise persisted in the presence of the glutamate NMDA and non-NMDA antagonists, APV (100 microM) and CNQX (10 microM), but it was blocked (n = 5) by a GABAA antagonist, bicuculline (10 microM). 4. The increase in inhibitory synaptic events resulted from an enhanced frequency of unitary IPSPs from 4.6 +/- 3.8 Hz in control to 17.2 +/- 12.5 Hz (n = 5) in serotonin, especially of large events. Serotonin caused no change in the amplitude and frequency of miniature synaptic events recorded in the presence of TTX (n = 5). The mean amplitude of unitary inhibitory postsynaptic potentials (IPSPs) increased from 1.37 +/- 0.35 mV in control to 3.67 +/- 1.38 mV in serotonin. The coefficient of variation of unitary IPSPs increased from 0.40 +/- 0.11 in control to 0.74 +/- 0.23 in serotonin when quantal size appeared unchanged. 5. The 5-HT3 agonist 2-methyl-serotonin (52 microM, n = 4) partially mimicked the effect of serotonin, increasing the inhibitory noise without affecting the pyramidal neurone conductance. The serotonin-induced facilitation of unitary IPSPs was blocked by the 5-HT3 antagonists ICS 205-930 (1-90 nM, n = 3) and metoclopramide (30 microM, n = 1). 6. These results suggest that serotonin directly excites GABAergic interneurones acting on a 5-HT3 receptor and consequently increasing the frequency of inhibitory synaptic events recorded in CA1 pyramidal cells.

2-Amino-5-phosphonovalerate↗

PubMed1987

[Growth of neurites and formation of connections in cultures of pteropodial mollusc neurons].

Dissociated neurons from the brain of pteropodial mollusc were cultivated in a 25% Leibovitz medium containing 2% of calf serum. Neurite outgrowth was observed in 1-30% of the neurons. It was maximum during the first 3 days. Neurite length reached 300 microns. Membrane potential of neurons was 40-60 mV; they generated single spikes or bursts of impulses. Intercellular connections were tested on the 3-4th days in 70 pairs of neurons with neurites overlapped. Electrical connections between the cells were observed in 20% of the pairs tested, and in 6% of pairs stimulation of one of the neurons evoked an inhibitory postsynaptic potential in the other.

Animals↗

PubMed1990

Foreign connections are formed in vitro by Aplysia californica interneuron L10 and its in vivo followers and non-followers.

Aplysia californica interneurone L10 forms a set of presynaptic connections with many postsynaptic 'follower' cells in the abdominal ganglion. These followers do not connect back to L10. The present study tests whether the direction and sign of these connections are obligatory and are reconstructed when neuronal processes regenerate in vitro. L10 was co-cultured with one of six different followers and two non-followers. 1. In vitro connections that preserve the sign of those formed in vivo were made by L10 onto neurones L11, L12 and L13. The connections consisted of inhibitory postsynaptic potentials (IPSPs) with characteristic fast and slow components. 2. In vitro connections that did not preserve the sign of connections found in vivo were made by L10 onto R15, R16 and L7. Neurones R15 and R16 receive excitatory inputs from L10 in vivo and L7 receives a dual-action input in vivo, with inhibition followed by excitation. A purely inhibitory connection from L10 was formed in vitro onto all these cells. 3. Connections that have never been observed in vivo in terms of both direction and sign were formed in vitro. Followers L7, L11, L12, L13 and R16 and non-follower L14A formed novel connections onto L10. All these connections were inhibitory and some were strong. For example, IPSPs with a magnitude of 20 mV were observed in L10 following a single action potential in L13. Our results show that identified Aplysia neurones can form stereotyped specific connections in vitro. The specificity is different from that in the intact ganglion. The ubiquity of novel connections suggests that restrictions imposed on synaptogenesis in the animal are distinct from those regulating synapse formation in culture.

Animals↗

PubMed2005

Effects and wavelet spectral entropy analysis of rhubarb extracts rhein on synaptic transmission in rat hippocampal ca1 area in vitro.

BACKGROUND: 5-dihydroxyanthraquinone-2-carboxylic acid (rhein) inhibits oxidoreduction induced by reducing nicotingamide adenine dinucleotide in the mitochondria and reducing reactive oxygen species, it also suppresses lipid peroxidation in rat brain homogenates. This study was to assess the effects of anthraquinone derivatives, rhein on synaptic transmission in the rat hippocampal CA1 pyramidal cell layer by intracellular recording. METHODS: The excitatory postsynaptic potential (EPSP) evoked by stimulation of the Schaffer collaterals in the presence of bicuculline (15 micromol/L) was depressed by application of rhein (0.3 - 30 micromol/L). The amplitude of the EPSP was restored within 20 minutes after removal of rhein from the supernatant. At a concentration of 30 micromol/L, rhein reduced the amplitude of the EPSP to 42% +/- 3.7% (n = 24) of the control. Subsequently, wavelet spectral entropy was used to analyze the EPSP. RESULTS: A strong positive correlation was observed between the wavelet spectral entropy and other parameters such as amplitude, slope of rising phase and slope of descending phase of the EPSP. The paired-pulse facilitation (PPF) of the EPSP was significantly increased by rhein (30 micromol/L). The inhibitory postsynaptic potential (IPSP) recorded in the presence of CNQX (20 micromol/L) and APV (40 micromol/L) is not altered by rhein (30 micromol/L). CONCLUSIONS: Rhein (30 micromol/L) can decrease the frequency but not the amplitude of the miniature EPSP (mEPSP). It is suggested that rhein inhibits excitatory synaptic transmission by decreasing the release of glutamate in rat hippocampal CA1 pyramidal neurons.

Animals↗

PubMed2004

Suppression of excitatory synaptic transmission can facilitate low-calcium epileptiform activity in the hippocampus in vivo.

It has been reported that the inhibitory postsynaptic potential (IPSP) is abolished before the excitatory postsynaptic potential (EPSP) when the extracellular concentration of Ca(2+) ([Ca(2+)](o)) is removed gradually in hippocampal slices. However, the low-Ca(2+) nonsynaptic epileptiform activity does not appear until the [Ca(2+)](o) is decreased to a level sufficient to depress the excitatory synaptic transmission. This suggests the hypothesis that the suppression of excitatory synaptic transmission itself could facilitate the generation of epileptiform activity. In the present study, we tested this hypothesis and developed a new model of nonsynaptic epileptiform activity by gradually raising the neuronal excitability and blocking the synaptic transmission with high K(+), zero Ca(2+) and calcium chelator ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the CA1 region of hippocampus in vivo. The changes of synaptic transmission and recurrent inhibitory activity during this process were evaluated by measuring the amplitude of the population spikes (PS) in response to paired-pulse orthodromic stimulation. The results show that the epileptiform activity appeared only when the excitatory synaptic transmission was depressed by further lowering [Ca(2+)](o) with EGTA. Similar epileptiform activity could be induced when EGTA was replaced by the excitatory postsynaptic amino acid antagonists D-(-)-2-amino-5-phosphonopentanoic acid (APV) plus 6,7-dinitroquinoxaline-2,3-dione (DNQX) or APV alone but not DNQX alone. The combination application of APV and cadmium enhanced the epileptiform activity. These results suggest that the suppression of excitatory synaptic transmission can facilitate the appearance of epileptiform activity in solution with high K(+) and low Ca(2+) in vivo. These data provide new information to be considered in the development of antiepileptic drugs. They also suggest a possible mechanism to explain the fact that low-frequency electrical stimulation can suppress epileptiform activity.

2-Amino-5-phosphonovalerate↗

PubMed1991

Analysis of Ia-inhibitory synaptic input to cat spinal motoneurons evoked by vibration of antagonist muscles.

1. Steady-state inhibitory postsynaptic potentials (IPSPs) were evoked in tibialis anterior and extensor digitorum longus motoneurons of the cat by using tendon vibration to activate Ia-afferent fibers from the antagonist medial gastrocnemius muscle. 2. The effective synaptic currents (IN) underlying the steady-state IPSPs were measured by the use of a modified voltage-clamp technique. The amplitudes of the effective synaptic currents (1.62 +/- 0.66 nA, mean +/- SD; n = 20) extended over a fivefold range (0.5-2.7 nA) but were not correlated with the intrinsic properties of the motoneurons or with putative motor unit type. 3. We calculated the synaptic conductance (GS) underlying the steady-state Ia IPSPs from measurements of motoneuron input conductance during the activation of the Ia synaptic input. As was expected from Ohm's law, the Ia-inhibitory GS and IN were correlated (r = 0.49; P less than 0.05). Like IN, GS (175 +/- 202 nS, mean +/- SD; n = 20) was not correlated with the intrinsic properties of the motoneurons. 4. As has been reported previously for transient Ia IPSPs, the amplitudes of the steady-state IPSPs were correlated with motoneuron input resistance (r = 0.74; P less than 0.001) and homonymous Ia excitatory postsynaptic synaptic potential (EPSP) amplitude (r = 0.72; P less than 0.001). 5. The amplitudes of the steady-state Ia IPSPs and the homonymous Ia EPSPs were plotted on logarithmic axes. The slope (0.59) was significantly less than 1, which indicates that the gradient of Ia inhibition across the motoneuron pool is less steep than that of Ia excitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

[Responses of neurons in the somato-sensory area I to noxious electric stimulation of nervus peroneus communis. The study of intracellular potentials].

Noxious electric stimulation of nervus peroneus communis (PN) results in pain. It hasn't been reported that the neurons in somatosensory area I (SI) may respond to the noxious stimulation. In this paper, using intracellular microelectrode technique, we have studied the responses of neurons in SI to noxious electric stimulating PN. 33 neurons were recorded in 18 cats. 16 neurons were related with the noxious stimulation. The responses of these neurons to noxious stimulation were mainly inhibitory postsynaptic potentials (IPSP). Some neurons responded with two IPSPs. A few neurons responded with EPSP (Excitatory postsynaptic potential)-IPSPs. The latencies of the first IPSPs were short (8.25 +/- 5.90ms) and showed that the first IPSPs might be induced by the input of A beta fiber. The latencies of the second IPSPs (In the neurons with two IPSPs) were long (60.33 +/- 6.62 ms) and showed that the second IPSPs might be induced by the input of A delta fiber. Above results show that: 1) SI neurons can respond to the noxious electric stimulation of PN. 2) The responses of SI neurons to the noxious stimulation were mainly IPSPs. 3) The second IPSPs might be related with pain.

Animals↗

PubMed2006

Excitatory and feed-forward inhibitory hippocampal synapses work synergistically as an adaptive filter of natural spike trains.

Short-term synaptic plasticity (STP) is an important mechanism for modifying neural circuits during computation. Although STP is much studied, its role in the processing of complex natural spike patterns is unknown. Here we analyze the responses of excitatory and inhibitory hippocampal synapses to natural spike trains at near-physiological temperatures. Our results show that excitatory and inhibitory synapses express complementary sets of STP components that selectively change synaptic strength during epochs of high-frequency discharge associated with hippocampal place fields. In both types of synapses, synaptic strength rapidly alternates between a near-constant level during low activity and another near-constant, but elevated (for excitatory synapses) or reduced (for inhibitory synapses) level during high-frequency epochs. These history-dependent changes in synaptic strength are largely independent of the particular temporal pattern within the discharges, and occur concomitantly in the two types of synapses. When excitatory and feed-forward inhibitory synapses are co-activated within the hippocampal feed-forward circuit unit, the net effect of their complementary STP is an additional increase in the gain of excitatory synapses during high-frequency discharges via selective disinhibition. Thus, excitatory and feed-forward inhibitory hippocampal synapses in vitro act synergistically as an adaptive filter that operates in a switch-like manner and is selective for high-frequency epochs.

Action Potentials↗

PubMed1999

GABA(B) receptor-mediated effects in human and rat neocortical neurones in vitro.

GABA(B) receptor-mediated responses were investigated in human and rat neocortical neurones in vitro by using intracellular recording. Human epileptogenic tissue and cortex from rats were compared for differences related to the cellular mechanisms of hyperexcitability. In both tissues, single stimuli of various intensities were used to compare basic properties of excitatory and inhibitory postsynaptic potentials (EPSP, IPSP). Paired stimuli, causing a decrease of a second IPSP, were used as an index of presynaptic activation of GABA(B) receptors. In neocortical neurones of rats, increasing intensities of stimulation elicited at low intensities (6-8 V) a fairly pure EPSP which was curtailed at higher stimulus intensities (10-14 V) by a GABA(A) receptor mediated IPSP (IPSP(A)). In all rat neocortical neurones the IPSP(A) was followed by a late inhibitory component (IPSP(B), time to peak about 150 ms) which was eliminated by the GABA(B) receptor antagonists CGP 35348 or CGP 55845A. On average, paired stimuli reduced the amplitude of a second IPSP(A) to 57% of the first (in the presence of 10 microM CNQX and 20 microM D-APV). Paired-pulse depression was only antagonized by CGP 55845A, but not by CGP 35348. The magnitude and time course of paired-pulse depression was markedly enhanced at lower temperatures. In human cortical neurones obtained following epilepsy surgery only low intensity stimuli (4 V) elicited EPSPs. Intermediate to higher stimulus intensities (8-10 V) elicited often all-or-none depolarization shifts or prolonged and increased EPSPs. Few neurones exhibited a sequence of EPSP and IPSPs comparable to that observed in rat neurones. Application of CGP 55845A caused little change in excitability near 150 ms, indicating that the IPSP(B) is weak. Paired-pulse depression of inhibition was small in most neurones, the second IPSPA was reduced to 82.8% of the first at a 500 ms interval (n = 6). Only two neurones exhibited a paired-pulse depression comparable to rat neurones. The consequences of GABA receptor-mediated paired-pulse depression on neuronal synchronisation are discussed towards the different cellular mechanisms of focal and bilateral synchronous epilepsies.

Animals↗

PubMed1987

Action and location of neuropeptide tyrosine (Y) on hippocampal neurons of the rat in slice preparations.

The action of bath applied NPY (1-1,000 nM) was investigated on hippocampal slices of the rat with extra- and intracellular recording. Neuropeptide Y (NPY) at 10-1,000 nM caused a concentration-dependent, long-lasting reduction of excitatory postsynaptic potentials (EPSPs) in the hippocampal subfield CA1 and the area dentata, and an even stronger reduction of population spikes. Paired pulse experiments with low intensity, stimulation-evoked PSPs showed a marked increase in facilitation in the presence of NPY, indicating a presynaptic action. Spontaneous burst firing of CA1 pyramidal cells in low calcium, high magnesium medium was reduced, indicating a partially postsynaptic inhibitory action of NPY on their dendrites. Intracellular recording from CA1 somata during NPY administration revealed a reduction of the amplitudes of excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequences in the absence of changes in membrane potential and conductance. Accommodation of firing during long depolarizing pulses and afterhyperpolarizations were unchanged. The innervation pattern of NPY immunoreactive fibers in the same regions was studied in slices adjacent to the ones used for electrophysiology by using antisera against NPY and light and electron microscopy. There is a dense innervation of CA1 by NPY-immunoreactive axons and terminals, particularly in the stratum moleculare. NPY-immunoreactive neurons are present in the stratum oriens and pyramidale. The NPY labeled axons of the stratum moleculare participate in numerous synaptic contacts with the smaller dendritic elements in this layer, many of which belong to pyramidal neurons. These observations provide evidence for a dendritic NPY-immunoreactive innervation of CA1 neurons, which is in keeping with the electrophysiological effects of NPY on pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

CGP 35348: a centrally active blocker of GABAB receptors.

The biochemical, electrophysiological and pharmacological properties of the new GABAB receptor blocker CGP 35348 are described. In a variety of receptor binding assays CGP 35348 showed affinity for the GABAB receptor only. CGP 35348 had an IC50 of 34 microM at the GABAB receptor. The compound antagonized (100, 300, 1000 microM) the potentiating effect of L-baclofen on noradrenaline-induced stimulation of adenylate cyclase in rat cortex slices. In electrophysiological studies CGP 35348 (10, 100 microM) antagonized the effect of L-baclofen in the isolated rat spinal cord. In the hippocampal slice preparation CGP 35348 (10, 30, 100 microM) blocked the membrane hyperpolarization induced by D/L-baclofen (10 microM) and the late inhibitory postsynaptic potential. CGP 35348 appeared to be 10-30 times more potent than the GABAB receptor blocker phaclofen. Ionophoretic and behavioural experiments showed that GABAB receptors in the brain were blocked after i.p. administration of CGP 35348. This compound may be of considerable value in elucidating the roles of brain GABAB receptors.

Adenylyl Cyclase Inhibitors↗

PubMed2000

Properties of solitary tract neurons receiving inputs from the sub-diaphragmatic vagus nerve.

Vagal afferents ascending from the gastrointestinal tract synapse on neurons in the nucleus of the solitary tract. Although these neurons constitute a significant proportion of solitary tract cells their firing behaviour and synaptic properties are not documented. Since gastrointestinal tract afferent termination sites overlap with regions mediating cardiorespiratory reflexes the possibility of convergence with afferents mediating cardiovascular and respiratory reflexes was proposed. Here we describe some electrophysiological and morphological properties of solitary tract neurons orthodromically driven from the subdiaphragmatic vagus nerves and assess possible convergent inputs from cardiorespiratory afferents. Whole-cell recordings of solitary tract neurons responding to electrical stimulation of the sub-diaphragmatic vagus nerves (0.1-1 ms; 1-10 V; 2-20 Hz) were made in a working heart-brainstem preparation of rat. Baroreceptors were stimulated by raising pressure in the aorta or carotid sinus, whereas aortic injection of sodium cyanide (0.05% solution 25-50 microl) was used to activate peripheral chemoreceptors. Phrenic nerve activity and heart rate were monitored continuously. Of 88 solitary tract neurons tested, 39 responded with an evoked excitatory synaptic potential following stimulation of the sub-diaphragmatic vagus nerves. Resting membrane potential and input resistance of sub-diaphragmatic vagus nerve driven solitary tract neurons were 53.2 +/- 0.5 mV and 291 +/- 17 Mohms, respectively (mean +/- S.E.M.). Response latencies to sub-diaphragmatic vagus nerve stimulation were divided into two groups: <20 ms (16.0 +/- 2 ms, n = 7; mean +/- S.E.M.) and >20 ms (77.3 +/- 5 ms, n = 32). One additional neuron displayed an evoked inhibitory postsynaptic potential (latency 175 ms). Nineteen neurons showed ongoing activity which consisted of either irregular single action potential firing (0.5-10 Hz; n = 12) or burst discharge (n = 7). Of 33 neurons tested, 17 showed spike frequency adaptation during injection of positive current, whereas 19 of 38 cells displayed rebound excitation following release from hyperpolarized potentials. There was no correlation between these properties and synaptic latencies. Ninety-one per cent of neurons tested displayed synaptic depression following paired pulse stimulation of the sub-diaphragmatic vagus nerve over intervals up to 500 ms. Stimulation of either baroreceptors (n = 31) or chemoreceptors (n = 36) failed to elicit a synaptic response in all sub-diaphragmatic vagus nerve-driven solitary tract neurons. Neurobiotin-labelled solitary tract neurons (n = 10) were from both latency groups and were located medial to the solitary tract at the level of area postrema, -0.3 mm to +1 mm from the obex. One cell was located in commissural subnucleus at midline, seven cells dorsal to the tractus solitarius and three ventral and medial to it. Soma sizes were 23 +/- 9.6 x 14 +/- 4.9 microm (range: 50 x 16 microm to 15 x 7 microm). The number of primary dendrites varied from three to five, secondary from one to eight and tertiary zero to four. Labelled axons were found in seven cells which ramified extensively in the solitary tract nucleus (n = 3) and/or branched extensively in the dorsal vagal motonucleus (n = 3) and/or projected towards the ventrolateral medulla (n = 3). We conclude that solitary tract neurons receiving signals from the sub-diaphragmatic vagus nerves (most likely from gastrointestinal tract structures) appear to be a distinct pool of neurons. There was a heterogeneity in terms of both their ongoing activity and projection targets but despite this, there were three consistent properties. First, sub-diaphragmatic vagus nerve evoked predominantly excitatory synaptic responses in solitary tract neurons; second, neurons exhibited lasting paired pulse depression following activation of sub-diaphragmatic vagus nerves; and third, sub-diaphragmatic vagus nerve-driven solitary tract neurons were

Afferent Pathways↗

PubMed1999

Decrease in inhibition in dentate granule cells from patients with medial temporal lobe epilepsy.

Alterations in synaptic inhibition are associated with epileptiform activity in several acute animal models; however, it is not clear if there are changes in inhibition in chronically epileptic tissue. We have used intracellular recordings from granule cells of patients with temporal lobe epilepsy to determine whether synaptic inhibition is compromised. Two groups of patients with medial temporal lobe epilepsy were used, those with medial temporal lobe sclerosis (MTLE), and those with extrahippocampal masses (MaTLE) where the cell loss and synaptic reorganization that characterize MTLE are not seen. Although the level of tonic inhibition at the somata was not significantly different in the two patient groups, there was a reduction in the conductance of polysynaptic perforant path-evoked fast and slow inhibitory postsynaptic potentials (IPSPs) (53% and 66%, respectively). We found that there was a comparable decrease in the monosynaptic IPSP conductances examined in the presence of glutamatergic antagonists as that seen for the polysynaptically evoked IPSPs. These data suggest that the decrease in inhibition seen in normal artificial cerebrospinal fluid in MTLE granule cells cannot be solely explained by a decrease in excitatory input onto inhibitory interneurons and may reflect changes at the interneuron-granule cells synapse or in the number of specific inhibitory interneurons.

2-Amino-5-phosphonovalerate↗