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PubMed1997

Distinct muscarinic receptor subtypes suppress excitatory and inhibitory synaptic responses in cortical neurons.

Simultaneous whole cell recordings from monosynaptically connected cortical cells were performed with the use of two patch pipettes to determine the effect of acetylcholine (ACh) on both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively) in cultured neurons from rat visual cortex. For 96% of EPSPs and 73% of IPSPs, ACh potently suppressed postsynaptic potentials in a dose-dependent manner. The estimated effective concentrations to produce half maximal response (EC50S) were 30 and 210 nM for EPSPs and IPSPs, respectively. To identify what subtypes of ACh receptors are involved in the suppression of postsynaptic potentials, three different, partially selective muscarinic receptor antagonists were used. According to the comparison of estimated Schild coefficients for each of the three antagonists against the suppression by ACh, EPSPs are most likely mediated by m4 receptors, and IPSPs by m1 receptors. When cells were treated with pertussis toxin, which inactivates m2 and m4 receptors while leaving m1, m3, and m5 receptors intact, 7 of 8 EPSPs were resistant to ACh whereas 8 of 12 IPSPs were still suppressed by ACh. This result supports the interpretation that the suppression of EPSPs was mediated by m4 receptors and that of IPSPs by m1 receptors. To obtain an indication as to whether ACh works presynaptically or postsynaptically, 1/CV2 analysis was carried out. The resultant diagonal alignment of the ratio of 1/CV2 plotted against the ratio of the amplitude of postsynaptic potentials suggests a presynaptic mechanism for the suppression of both EPSPs and IPSPs. In addition, in many cases a large synaptic suppression was observed without an obvious change in the input resistance. Furthermore, in one case where a single inhibitory driver cell was recorded with three different follower cells sequentially, none of the three IPSPs was suppressed by ACh, providing additional support for the presynaptic localization of ACh action. These results suggest that in cerebral cortex ACh has, in addition to its direct facilitatory effect via m3 pharmacology, a suppressive effect on EPSPs and IPSPs via m1 and m4 muscarinic receptors, respectively, probably with a presynaptic site of action. Separation of the actions of ACh into different receptor-second messenger pathways with potential for independent interactions with other neuromodulatory systems may be an important aspect of the mechanism of cholinergic regulation of functional state in cortex. Separation of cholinergic effects at different receptors might also offer a means for selective pharmacological intervention in disorders of sleep or memory.

Acetylcholine↗

PubMed2004

Membrane potential changes in vocal cord tensor motoneurons during breathing, vocalization, coughing and swallowing in decerebrate cats.

We studied the patterns of membrane potential changes in vocal cord tensor motoneurons, i.e. cricothyroid muscle motoneurons (CTMs), during fictive breathing, vocalization, coughing, and swallowing in decerebrate paralyzed cats to determine the nature of central drives to CTMs during these behaviors. CTMs were identified by antidromic activation from the superior laryngeal nerve. During breathing, CTMs always depolarized during the inspiratory phase, and sometimes depolarized during the expiratory phase as well. During vocalization, CTMs strongly depolarized. During coughing, CTMs exhibited depolarizations during both inspiratory and expiratory phases, but it was interrupted by a transient repolarization between the last part of the inspiratory phase and the first part of the abdominal burst during which chloride-dependent inhibitory postsynaptic potentials were revealed. During swallowing, most CTMs hyperpolarized, and this hyperpolarization was sometimes followed by a weak depolarization. We conclude that the main role of the cricothyroid muscle is vocalization but the functional roles in coughing and swallowing are minor, and that the CTM activity during resting breathing and vocalization are primarily controlled by excitatory inputs, while during coughing and swallowing, inhibitory inputs play roles in shaping membrane potential trajectories.

Analysis of Variance↗

PubMed1981

Penicillin- and barium-induced epileptiform bursting in hippocampal neurons: actions on Ca++ and K+ potentials.

Both barium (Ba++) and penicillin produce spontaneous epileptiform burst generation in hippocampal neurons in vitro. Recent investigations suggest that Ba++ acts by both adding to a calcium (Ca++)-mediated depolarization and reducing potassium (K+) conductance. In contrast, it has been proposed that penicillin produces burst generation by attenuating inhibitory postsynaptic potentials. However, some evidence suggests that penicillin may also directly alter intrinsic membrane properties. We therefore compared the actions of penicillin and Ba++ on three intrinsic Ca++- or K+-mediated membrane events, namely, CA++ spikes, Ca++-dependent anomalous rectification, and K+-dependent afterhyperpolarization. Ba++ augmented the Ca++ potentials and attenuated the K+-dependent afterhyperpolarization; penicillin had no demonstrable effect on these events. Ba++ produced rhythmical burst firing and oscillations of the membrane potentials, while penicillin caused sporadic burst generation followed by a longlasting afterhyperpolarization. Synchronized, orthodromically evoked burst firing occurred after exposure to penicillin but not to Ba++. Ba++ and penicillin are prototypes of agents which induce epileptogenesis in mammalian cortical neurons by two different but probably interrelated mechanisms. Ba++ causes burst generation by disrupting a delicate balance between depolarizing Ca++ potentials and repolarizing, hyperpolarizing K+ potentials. Penicillin does not affect Ca++- or K+-mediated membrane events; other data suggest that it produces burst generation in hippocampal pyramidal neurons by attenuating gamma-aminobutyric acid-mediated synaptic inhibition, which in turn ordinarily limits intrinsic bursting.

Action Potentials↗

PubMed1994

Repetitive stimulation induced potentiation of excitatory transmission in the rat dorsal horn: an in vitro study.

1. The effects of repetitive stimulation of primary afferents in lumbar dorsal roots on synaptic transmission in the dorsal horn (DH) were studied in a rat spinal cord slice-dorsal root ganglion (DRG)-peripheral nerve trunk preparation by the use of intracellular recording from neurons (n = 115) of the spinal dorsal horn (depth 147 +/- 139, mean +/- SD). All DH neurons were excited synaptically by electrical stimulation of the dorsal root or the peripheral nerve trunk. The electrical shocks were calibrated to produce activation either of large fibers (10-20 V, 0.02 ms) or the whole fiber population including unmyelinated afferents (supramaximal stimulus: > 35 V, 0.5 ms). Postsynaptic potentials induced by low intensity repetitive stimulation of primary afferents at frequencies below 5 Hz failed to produce a prolonged change in the resting membrane potential. In 97/115 DH neurons, slow excitatory postsynaptic potentials (EPSP)--evoked by high intensity low-frequency repetitive stimulation (0.1-2 Hz) of primary afferents--summated, producing a prolonged cumulative depolarization. In the remaining 18/115 DH neurons, high intensity low-frequency stimulation produced a cumulative hyperpolarizing response. 2. In 22 of 97 neurons that responded to high intensity repetitive stimulation with a cumulative depolarization, wind-up in the firing of action potentials was recorded. In all but two experiments, neurons that responded with wind-up to stimulation of one root responded with wind-up to stimulation of the adjacent dorsal root. In 14/22 wind-up neurons, the synaptic response to high intensity stimulation of primary afferents was composed of a short latency EPSP, followed by an inhibitory postsynaptic potential (IPSP), followed by a slow EPSP. The decrease of the amplitude and duration of the IPSP obtained during train stimulation did not seem to contribute to facilitation of transmission induced by repetitive stimulation. 3. The wind-up in firing of action potentials was followed by a prolonged potentiation of synaptic transmission in tetanized synapses. A test of other, adjacent primary afferents revealed that these synapses in the neurons in the superficial laminae had not undergone potentiation. This "synaptic specificity" of post-wind-up potentiation suggested that the mechanism for the induction of stimulation-dependent changes in the excitability of the DH neuron is presynaptic to the recorded-from neuron. 4. In a concentration of 0.5 microM and higher, tetrodotoxin (TTX) applied to sensory neurons selectively blocked action potentials in large myelinated primary afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1998

Characterization of neuronal migration disorders in neocortical structures. II. Intracellular in vitro recordings.

Neuronal migration disorders (NMD) are involved in a variety of different developmental disturbances and in therapy-resistant epilepsy. The cellular mechanisms underlying the pronounced hyperexcitability in dysplastic cortex are not well understood and demand further clinical and experimental analyses. We used a focal freeze-lesion model in cerebral cortex of newborn rats to study the functional consequences of NMD. Intracellular recordings from supragranular regular spiking cells in cortical slices from adult sham-operated rats revealed normal passive and active intrinsic membrane properties and normal stimulus-evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively). Regular spiking neurons recorded in rat dysplastic cortex showed on average a significantly smaller action potential amplitude, a slower spike rise, and a less steep primary frequency-current relationship. Stimulus-elicited EPSPs in NMD-affected cortex consisted of multiphasic burst discharges, which coincided with extracellular field potentials and lasted 150-800 ms. These epileptiform responses could be recorded at membrane potentials between -50 and -110 mV and were blocked by -2-amino-5-phosphonovaleric acid (APV), indicating the involvement of N-methyl--aspartate (NMDA) receptors. Isolated NMDA-mediated and APV-sensitive EPSPs could be recorded at membrane potentials negative to -70 mV, suggesting that NMDA receptors are activated at relatively negative membrane potentials. In comparison with the controls, polysynaptic IPSPs mediated by the gamma-aminobutyric acid (GABA) type A and B receptor were either absent or reduced in peak conductance in microgyric cortex by 27% (P < 0.05) and 17%, respectively. However, monosynaptic IPSPs recorded in the presence of ionotropic glutamate receptor antagonists revealed a similar efficacy in NMD and control cortex, indicating that GABAergic neurons in microgyric cortex get a weaker excitatory input. Our data indicate that the expression of epileptiform activity in NMD-affected cortex rather results from an imbalance between excitatory and inhibitory synaptic transmission than from alterations in the intrinsic membrane properties. This imbalance is caused by an increase in NMDA-receptor-mediated excitation in pyramidal neurons and a concurrent decrease of glutamatergic input onto inhibitory interneurons.

2-Amino-5-phosphonovalerate↗

PubMed2004

Neurokinin-1 and -3 receptor blockade inhibits slow excitatory synaptic transmission in myenteric neurons and reveals slow inhibitory input.

Recent studies have shown that tachykinins mediate slow synaptic transmission to myenteric AH (afterhyperpolarising) neurons via neurokinin-3 receptors (NK(3)R). This study investigated a similar role for neurokinin-1 receptors (NK(1)R) and compared the effect of selective receptor antagonists on non-cholinergic slow excitatory post-synaptic potentials (EPSPs) recorded in myenteric AH neurons of the guinea-pig ileum. Slow EPSPs evoked by electrical stimulation of circumferentially oriented presynaptic nerves were mimicked by application of senktide, an NK(3)R agonist. [Sar(9),Met(O(2))(11)]-substance P, an NK(1)R agonist, depolarised a smaller number of neurons. SR142801, a selective NK(3)R antagonist (100 nM), inhibited slow EPSPs and responses to senktide, but had no effect on depolarisations evoked by forskolin, an activator of adenylate cyclase. SR140333, a selective NK(1)R antagonist, inhibited slow EPSPs in a subset of neurons and blocked responses to [Sar(9),Met(O(2))(11)]-substance P, but not to senktide or forskolin. Slow EPSPs that were predominantly mediated by NK(1)R had significantly shorter latencies than those due to activation of NK(3)R. After blockade of slow EPSPs, slow hyperpolarizing responses to presynaptic nerve stimulation were revealed in one-third of neurons. These events, which were associated with a decrease in input resistance and blocked by tetrodotoxin, were equated with slow inhibitory postsynaptic potentials. They were abolished by the 5-hydroxytryptamine(1A) receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190), but unaffected by phentolamine, an alpha-adrenoceptor antagonist. In conclusion, these results provide the first direct evidence that NK(1)R mediate some slow excitatory synaptic input to myenteric AH neurons, and suggest that NK(1)R and NK(3)R activate distinct signal transduction pathways. These results also demonstrate that slow inhibitory synaptic transmission, which may be mediated by 5-hydroxytryptamine, is more prevalent in the myenteric plexus than previously indicated.

Adrenergic alpha-Antagonists↗

PubMed1993

Influence of hypoxia on excitation and GABAergic inhibition in mature and developing rat neocortex.

To analyze the functional consequences of hypoxia on the efficacy of intracortical inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), extra- and intracellular recordings were obtained from rat primary somatosensory cortex in vitro. Hypoxia, induced by transient N2 aeration, caused a decrease in stimulus-evoked inhibitory postsynaptic potentials (IPSPs), followed by a pronounced anoxic depolarization. Upon reoxygenation, the fast (f-) and long-latency (l-) IPSP showed a positive shift in the reversal potential by 24.4 and 14.9 mV, respectively. The peak conductance of the f- and l-IPSP was reversibly reduced in the postanoxic period by 72% and 94%, respectively. Extracellular field potential recordings and application of a paired-pulse inhibition protocol confirmed the enhanced sensitivity of inhibitory synaptic transmission for transient oxygen deprivation. Intracellular recordings from morphologically or electrophysiologically identified interneurons did not reveal any enhanced susceptibility for hypoxia as compared to pyramidal cells, suggesting that inhibitory neurons are not selectively impaired in their functional properties. Intracellularly recorded spontaneous IPSPs were transiently augmented in the postanoxic period, indicating that presynaptic GABA release was not suppressed. Developmental studies in adult (older than postnatal day 28), juvenile (P14-18), and young (P5-8) neocortical slices revealed a prominent functional resistance of immature tissue for hypoxia. In comparison with adult cortex, the hypoxia-induced reduction in excitatory and inhibitory synaptic transmission was significantly smaller in immature cortex. Our data indicate a hypoxia-induced distinct reduction of postsynaptic GABAergic mechanisms, leading to the manifestation of intracortical hyperexcitability as a possible functional consequence.

2-Amino-5-phosphonovalerate↗

PubMed2000

Spontaneous synaptogenesis in ex vivo sympathetic ganglion and the blockade by serum treatment.

Central denervation for more than 1 month has been shown to cause an increase in the number of adrenergic synapses in sympathetic ganglia in vivo. Here, we report several lines of evidence that adrenergic synapses may be generated de novo in ex vivo superior cervical ganglion (SCG) of adult rats only several hours after the isolation. Structures immunoreactive for synaptophysin, a marker of presynaptic elements, were drastically decreased 6 days after the preganglionic denervation. A significant increase in number of synaptophysin positive boutons was observed over 3-8 hours in the denervated SCGs maintained ex vivo at 36 degrees C in oxygenated physiologic saline, and this increase was blocked by adding normal serum in the saline. Electron microscopic analysis confirmed that the number of adrenergic synapses specifically labeled with 5-hydroxydopamine was increased by several-fold under the same condition. Intracellular labeling of SCG neurons revealed an increase in the incidence (from 8 to 50%) of neurons having dendritic plexus after the in vitro incubation. No evidence of axonal sprouting within the ganglion was observed. Intracellular recordings from single neurons of denervated SCGs revealed that maximum amplitudes of inhibitory postsynaptic potentials, which were completely blocked by yohimbine, an alpha2-adrenoceptor antagonist, in response to focal stimulation were increased over the several hours. These results suggest that dendrites of SCG neurons rapidly develop and exhibit local efferent characteristics that underlie the inhibitory synaptic transmission once they are subjected to serum deprivation.

Animals↗

PubMed1996

Chronic epilepsy with damage restricted to the hippocampus: possible mechanisms.

We studied the time course and possible mechanisms of the development of chronic epilepsy following unilateral stimulation of the perforant path. After 24 h of perforant path stimulation by a modified Sloviter method, lesions were restricted to the hippocampus, except for 2 of 24 rats with minimal entorhinal neuronal injury in layer 3. Lesions were exclusively ipsilateral in the polymorph layer of the hilus and in CA4-CA3C, predominantly ipsilateral in CA3, in CA1 and in the granule cell layer. Feedforward and feedback inhibition were studied by paired pulse stimulation. In the week following inhibition, there was complete loss of GABAA-mediated, short interstimulus interval (ISI)-dependent inhibition and frequency-dependent inhibition, and also of GABAB-mediated long ISI-dependent inhibition. Yet no spontaneous seizures were observed at that time. In the next four weeks, we saw no evidence of increasing excitatory drive such as would be expected from recurrent mossy fiber sprouting. On the contrary, there was progressive return of inhibition. By four weeks post-lesion, the majority of animals had developed spontaneous recurrent seizures, and/or seizures on 2 Hz stimulation (never seen in controls), in spite of complete or near-complete recovery of short ISI-dependent, GABAA-mediated inhibition. A small but significant loss of frequency-dependent inhibition persisted, but individual animals with complete recovery of frequency-dependent inhibition showed spontaneous seizures, suggesting that loss of GABAA-mediated inhibition was not the direct cause of chronic epilepsy. GABAB-mediated, long ISI-dependent inhibition continued to show a significant loss. The ratio of the population spike amplitude at 250 microA to the maximal population spike amplitude, a measure of granule cell excitability, was unchanged immediately after stimulation, but increased in the next few weeks in a manner identical to that seen in kindling, suggesting the possibility that during the transient loss of inhibition, spontaneous kindling had occurred. Intracellular recordings from granule cells in hippocampal slices prepared from these animals showed a significant loss of GABAB-mediated slow inhibitory postsynaptic potentials (IPSPs). These data show that the sequellae of unilateral status epilepticus with damage restricted to the hippocampus are sufficient to cause chronic recurrent seizures. There is a possibility that chronic epilepsy is not the direct result of the loss of inhibitory drive or of a sprouting-induced increase in excitatory drive, but represents plastic changes akin to spontaneous kindling, possibly facilitated by loss of GABAB-mediated inhibition.

Animals↗

PubMed2001

Basic principles of synaptic physiology illustrated by a computer model.

A computer model is described that simulates many basic aspects of chemical synapse physiology. The model consists of two displays, the first being a pictorial diagram of the anatomical connections between two presynaptic neurons and one postsynaptic neuron. Either or both of the presynaptic cells can be stimulated from a control panel with variable control of the number of pulses and firing rate; the resulting presynaptic action potentials are animated. The second display plots the membrane potential of the postsynaptic cell versus time following presynaptic stimulation. The model accurately simulates temporal and spatial summation when the presynaptic cells are arranged and stimulated in parallel and simulates presynaptic inhibition when they are arranged and stimulated in series. Excitatory and inhibitory postsynaptic potentials can be demonstrated by altering the nature of the ionic conductance change occurring on the postsynaptic cell. The effects on summation of changing length constant or time constant of the postsynaptic cell can also be illustrated. The model is useful for teaching these concepts to medical, graduate, or undergraduate students and can also be used as a self-directed computer laboratory exercise. It is available for free download from the internet.

Computer Simulation↗

PubMed1984

Transmitter identification of pyloric neurons: electrically coupled neurons use different transmitters.

The neurotransmitters mediating the synaptic interactions among the neurons of the pyloric system of the stomatogastric ganglion (STG) of the lobster, Panulirus interruptus, were examined using a combination of electrophysiological, pharmacological, and biochemical techniques. Iontophoretically applied L-glutamate inhibited all motor neurons of the pyloric system. This inhibitory response was blocked by low concentrations of picrotoxin but unaffected by atropine. The anterior burster (AB) interneuron, pyloric dilator (PD) motor neurons, and ventricular dilator (VD) motor neuron were depolarized and excited by iontophoretically applied acetylcholine (ACh). The lateral pyloric (LP) and pyloric (PY) constrictor motor neurons were inhibited by ACh and by the cholinergic agonist, carbachol. These inhibitory cholinergic responses were blocked by atropine but not by picrotoxin. The inhibitory postsynaptic potentials (IPSPs) evoked by the constrictor motor neurons were blocked by picrotoxin but not by atropine. Taken together with previously published data (15, 18), this suggests that the constrictor motor neurons release glutamate at both their excitatory neuromuscular junctions and their inhibitory intraganglionic junctions. The lucifer yellow photoinactivation technique (27) was used to study separately the neurotransmitters released by the electrically coupled PD and AB neurons. The AB-evoked IPSPs were blocked by picrotoxin but not by atropine. The PD-evoked IPSPs were blocked by atropine and other muscarinic antagonists but not by picrotoxin. Somata of PD neurons contained choline acetyltransferase (CAT) activity, but somata of AB neurons contained no detectable CAT activity. On the basis of the data in this paper and previously published data (17, 18), we conclude that the PD neurons release ACh at both their excitatory neuromuscular junctions and their inhibitory intraganglionic connections. Although the AB neuron is electrically coupled to the PD neurons, the AB neuron is not cholinergic. Glutamate is a likely transmitter candidate for the AB neuron. These data show that electrically coupled neurons can release different transmitters. Furthermore, these data show that an IPSP can be the result of the combined actions of two different neurotransmitters, each released from a different neuron. The functional consequences of these conclusions are explored in the following papers (9, 22).

Acetylcholine↗

PubMed1986

Neuropharmacology of supraoptic nucleus neurons: norepinephrine and gamma-aminobutyric acid receptors.

The neurosecretory neurons in the mammalian hypothalamic supraoptic nucleus receive prominent GABAergic and noradrenergic projections arising from local interneurons and the A1 cells in the ventrolateral medulla, respectively. Intracellular recordings in in vitro perfused hypothalamic explants reveal an abundance of spontaneous inhibitory postsynaptic potentials (IPSPs) and a compound IPSP after electrical stimulation in the diagonal band of Broca area. The sensitivity of both spontaneous and evoked IPSPs to intracellular chloride injection, bicuculline, and pentobarbital is consistent with a GABA-activated, chloride-mediated inhibitory synaptic input. Parallel changes in membrane voltage and conductance are present during applications of GABA and muscimol, with similar sensitivity to ionic manipulation, bicuculline, and pentobarbital. These observations contrast with the consistently excitatory effects that follow either the stimulation of A1 cells or the application of norepinephrine and alpha 1-adrenergic agonists. Norepinephrine induces membrane depolarizations and bursting activity patterns that are blocked by the selective alpha 1 antagonist prazosin. Membrane response to norepinephrine is voltage dependent and is associated with little change in conductance. GABA and norepinephrine are proposed as transmitters in the final central pathways that mediate information to supraoptic vasopressinergic neurons from peripheral baroreceptors and chemoreceptors, respectively.

Animals↗

PubMed1997

Fast (mainly 30-100 Hz) oscillations in the cat cerebellothalamic pathway and their synchronization with cortical potentials.

1. Intracellular recordings from 216 thalamocortical (TC) neurones in the ventrolateral (VL) nucleus of intact-cortex and decorticated cats under ketamine-xylazine anaesthesia revealed spontaneously occurring fast oscillations (mainly 30-100 Hz) in 86% of investigated cells. The fast depolarizing events consisted of excitatory postsynaptic potentials (EPSPs), giving rise to fast prepotentials (FPPs) in 22% of neurones, which eventually lead to full-blown action potentials. The frequency of fast events changed by factors of 2-5 in periods as short as 0.3-1.0 s. 2. The spontaneous oscillations were similar to responses evoked in VL relay neurones by stimuli to the afferent cerebellofugal axons in brachium conjunctivum (BC) and were strikingly reduced or abolished after electrolytic lesion of BC axons. 3. The amplitude and duration of fast depolarizing events were significantly reduced during the descending phase of the inhibitory postsynaptic potentials (IPSPs) in TC cells, related to spontaneous spindles or evoked by local thalamic stimulation. 4. Averaged field potentials recorded from motor cortex and triggered by EPSPs and/or action potentials of intracellularly recorded VL cells demonstrated that both spontaneous and BC-evoked fast depolarizations in VL relay neurones were coherent with fast rhythms in cortical area 4. 5. These results show that, in addition to the thalamic and cortical generation sites of the fast (so-called gamma) oscillations, prethalamic relay stations, such as deep cerebellar nuclei, are major contributors to the induction of fast rhythms which depend on the depolarization of thalamic and cortical neurones and which represent a hallmark of brain activation patterns.

Action Potentials↗

PubMed1981

Effects of opioid peptides on synaptic potentials in explants of rat hippocampus.

Bath application of 10(-8) M FK 33-824 (an enkephalin analogue) and 10(-7) M beta-endorphin reversibly induced stimulus-evoked bursting activity with depolarization shifts in cultured hippocampal pyramidal cells. Statistical analysis of the data revealed that in the majority of cells, inhibitory postsynaptic potentials were markedly decreased and excitatory postsynaptic potentials increased prior to the development of bursting activity, although some inhibition persisted in cells exposed to opioid peptides. In a minority of cells, no alteration in synaptic potentials were observed to precede the stimulus-evoked bursts induced by the opioid peptides.

Action Potentials↗

PubMed1997

Novel glutamate- and GABA-independent synaptic depolarization in granule cells of guinea-pig hippocampus.

1. Dual intracellular recordings of granule cells, hilar interneurons and CA3 pyramidal cells were performed in transverse slices of guinea-pig hippocampus. At resting membrane potential, in the presence of 4-aminopyridine, ionotropic glutamate receptor antagonists and the GABAA receptor antagonist bicuculline, granule cells showed spontaneous, large amplitude depolarizations correlated with synchronous bursting activity of interneurons. 2. Under these conditions, pyramidal cells exhibited large amplitude monophasic GABAB inhibitory postsynaptic potentials (IPSPs) synchronous with the GABAergic interneuron burst discharges. The granule cells also received a GABAB input, which was evident only when the neurons were depolarized by DC injection. The GABAB receptor antagonist CGP 55,845A (CGP) blocked the GABAB IPSPs in both pyramidal cells and granule cells; however, the depolarizing potential in granule cells was unaffected by the drug. 3. The granule cells depolarization in the presence of CGP was monophasic and exhibited linear voltage dependence with a reversal potential around -40 mV, suggesting that it was generated by a synaptic input activating a mixed cationic current. 4. The granule cell depolarization was abolished following the addition of tetrodotoxin to the bath. In addition, perfusing the slice with a low Ca(2+)-containing solution (0.5 mM Ca(2+)-10 mM Mg2+) also abolished the granule cell depolarization, confirming the synaptic origin of the event. 5. (S)-Methyl-4-carboxyphenylglycine, L-(+)-2-amino-3-phosphonopropionic acid, propranolol and atropine did not affect the granule cell depolarization, indicating that metabotropic glutamate receptors, beta-adrenergic receptors and muscarinic cholinergic receptors were not involved in generating the granule cell depolarizing synaptic response. 6. These findings indicate that, in the absence of both glutamatergic and GABAergic inputs, synchronous interneuronal activity can produce a depolarizing synaptic response in granule cells. The neurochemical responsible for the depolarization is currently under investigation.

Animals↗

PubMed2001

The role of sensory signals from the insect coxa-trochanteral joint in controlling motor activity of the femur-tibia joint.

Interjoint coordination in multi-jointed limbs is essential for the generation of functional locomotor patterns. Here we have focused on the role that sensory signals from the coxa-trochanteral (CT) joint play in patterning motoneuronal activity of the femur-tibia (FT) joint in the stick insect middle leg. This question is of interest because when the locomotor system is active, movement signals from the FT joint are known to contribute to patterning of activity of the central rhythm-generating networks governing the CT joint. We investigated the influence of femoral levation and depression on the activity of tibial motoneurons. When the locomotor system was active, levation of the femur often induced a decrease or inactivation of tibial extensor activity while flexor motoneurons were activated. Depression of the femur had no systematic influence on tibial motoneurons. Ablation experiments revealed that this interjoint influence was not mediated by signals from movement and/or position sensitive receptors at the CT joint, i.e., trochanteral hairplate, rhombal hairplate, or internal levator receptor organ. Instead the influence was initiated by sensory signals from a field of campaniform sensillae, situated on the proximal femur (fCS). Selective stimulation of these fCS produced barrages of inhibitory postsynaptic potentials (IPSPs) in tibial extensor motoneurons and activated tibial flexor motoneurons. During pharmacologically activated rhythmic activity of the otherwise isolated mesothoracic ganglion (pilocarpine, 5 x 10(-4) M), deafferented except for the CT joint, levation of the femur as well had an inhibitory influence on tibial extensor motoneurons. However, the influence of femoral levation on the rhythm generated was rather labile and only sometimes a reset of the rhythm was induced. In none of the preparations could entrainment of rhythmicity by femoral movement be achieved, suggesting that sensory signals from the CT joint only weakly affect central rhythm-generating networks of the FT joint. Finally, we analyzed the role of sensory signals from the fCS during walking by recording motoneuronal activity in the single middle leg preparation with fCS intact and after their removal. These experiments showed that fCS activity plays an important role in generating tibial motoneuron activity during the stance phase of walking.

Animals↗

PubMed2003

Nature of inhibitory postsynaptic activity in developing relay cells of the lateral geniculate nucleus.

Using intracellular recordings in an isolated (in vitro) brain stem preparation, we examined the inhibitory postsynaptic responses of developing neurons in the dorsal lateral geniculate nucleus (LGN) of the rat. As early as postnatal day (P) 1-2, 31% of all excitatory postsynaptic (EPSP) activity evoked by electrical stimulation of the optic tract was followed by inhibitory postsynaptic potentials (IPSPs). By P5, 98% of all retinally evoked EPSPs were followed by IPSP activity. During the first postnatal week, IPSPs were mediated largely by GABA(A) receptors. Additional GABA(B)-mediated IPSPs emerged at P3-4 but were not prevalent until after the first postnatal week. Experiments involving the separate stimulation of each optic nerve indicated that developing LGN cells were binocularly innervated. At P11-14, it was common to evoke EPSP/IPSP pairs by stimulating either the contralateral or ipsilateral optic nerve. During the third postnatal week, binocular excitatory responses were encountered far less frequently. However, a number of cells still maintained a binocular inhibitory response. These results provide insight about the ontogeny and nature of postsynaptic inhibitory activity in the LGN during the period of retinogeniculate axon segregation.

Animals↗

PubMed2000

Taurine activates GABA(A) but not GABA(B) receptors in rat hippocampal CA1 area.

We investigated if taurine, an endogenous GABA analog, could mimic both hyperpolarizing and depolarizing GABA(A)-mediated responses as well as pre- and postsynaptic GABA(B)-mediated actions in the CA1 region of rat hippocampal slices. Taurine (10 mM) perfusion induced changes in membrane potential and input resistance that are compatible with GABA(A) receptor activation. Local pressure application of taurine and GABA from a double barrel pipette positioned along the dendritic shaft of pyramidal cells revealed that taurine evoked a very small change of membrane potential and resistance compared with the large changes induced by GABA in these parameters. Moreover, in the presence of GABA(A) antagonists, local application of GABA on the dendrites evoked a GABA(B)-mediated hyperpolarization while taurine did not induce any change. Taurine neither mimicked baclofen inhibitory actions on presynaptic release of glutamate and GABA as judging by the lack of taurine effect on paired-pulse facilitation ratio and slow inhibitory postsynaptic potentials, respectively. These results show that taurine mainly activates GABA(A) receptors located on the cell body, indicating therefore that if taurine has any action on the dendrites it will not be mediated by either GABA(A) or GABA(B) receptors activation.

2-Amino-5-phosphonovalerate↗