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PubMed1988

Activation of protein kinase C promotes glutamate-mediated transmission at the neuromuscular junction of the mealworm.

1. Actions of protein kinase C activators, 1,2-oleoylacetylglycerol (OAG) and 12-O-tetradecanoylphorbol-13-acetate (TPA), on the glutamate-mediated neuromuscular transmission in the mealworm, Tenebrio molitor, were studied by the microelectrode current-clamp and voltage-clamp techniques. 2. The activators OAG and TPA stimulate the evoked and spontaneous transmitter releases from the presynaptic terminal, as evidenced by an increase in the quantum content estimated by the number of failures of extracellular excitatory postsynaptic potentials (EPSPs), and in the frequency of miniature EPSPs. 3. Both OAG and TPA act on the postsynaptic membrane to enhance responses to the transmitter L-glutamate. Protein kinase C activators increased the apparent maximum of the ionophoretic dose-response curve for glutamate-induced depolarization, without affecting the reversal potential and the voltage-dependent decay rate for the excitatory postsynaptic current (EPSC) under voltage-clamp conditions. 4. The postsynaptic effect of OAG and TPA is distinctly different from that of activators of cyclic nucleotide-dependent protein kinases, such as octopamine, forskolin, CPT-cyclic AMP (8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate), and 8-bromo-cyclic GMP (8-bromoguanosine 3',5'-cyclic monophosphate) which decreased the postsynaptic sensitivity to L-glutamate. 5. I suggest that the responsiveness of the receptor to L-glutamate is under the control of these counteracting enzyme systems in the insect neuromuscular junction.

Action Potentials↗
PubMed2004

Developmental changes in release properties of the CA3-CA1 glutamate synapse in rat hippocampus.

Developmental changes in release probability (Pr) and paired-pulse plasticity at CA3-CA1 glutamate synapses in hippocampal slices of neonatal rats were examined using field excitatory postsynaptic potential (EPSP) recordings. Paired-pulse facilitation (PPF) at these synapses was, on average, absent in the first postnatal week but emerged and became successively larger during the second postnatal week. This developmental increase in PPF was associated with a reduction in Pr, as indicated by the slower progressive block of the N-methyl-D-aspartate (NMDA) EPSP by the noncompetitive NMDA receptor antagonist MK-801. This developmental reduction in Pr was not homogenous among the synapses. As shown by the MK-801 analysis, the Pr heterogeneity observed among adult CA3-CA1 synapses is present already during the first postnatal week, and the developmental Pr reduction was found to be largely selective for synapses with higher Pr values, leaving Pr of the vast majority of the synapses essentially unaffected. A reduction in Pves, the release probability of the individual vesicle, possibly caused by reduction in Ca2+ influx, seems to explain the reduction in Pr. In vivo injection of tetanus toxin at the end of the first postnatal week did not prevent the increase in PPF, indicating that this developmental change in release is not critically dependent on normal neural activity during the second postnatal week.

Aging↗
PubMed1998

Target neuron specification of short-term synaptic facilitation and depression in the cricket CNS.

We investigated the role of retrograde signals in the regulation of short-term synaptic depression and facilitation by characterizing the form of plasticity expressed at novel synapses on four giant interneurons in the cricket cercal sensory system. We induced the formation of novel synapses by transplanting a mesothoracic leg and its associated sensory neurons to the cricket terminal abdominal segment. Axons of ectopic leg sensory neurons regenerated and innervated the host terminal abdominal ganglion forming monosynaptic connections with the medial giant interneuron (MGI), lateral giant interneuron (LGI), and interneurons 7-1a and 9-2a. The plasticity expressed by these synapses was characterized by stimulating a sensory neuron with pairs of stimuli at various frequencies or with trains of 10 stimuli delivered at 100 Hz and measuring the change in excitatory postsynaptic potential amplitude recorded in the postsynaptic neuron. Novel synapses of a leg tactile hair on 7-1a depressed, as did control synapses of cercal sensory neurons on this interneuron. Novel synapses of leg campaniform sensilla (CS) sensory neurons on MGI, like MGI's control synapses, always facilitated. The form of plasticity expressed by novel synapses is thus consistent with that observed at control synapses. Leg CS synapses with 9-2a also facilitated; however, the plasticity expressed by these sensory neurons is dependent on the identity of the postsynaptic cell since the synapses these same sensory neurons formed with LGI always depressed. We conclude that the form of plasticity expressed at these synaptic connections is determined retrogradely by the postsynaptic cell.

Abdomen↗
PubMed2004

The anticonvulsant action of propofol on epileptiform activity in rat hippocampal slices.

We used extracellular electrophysiological recordings from the CA1 region in rat hippocampal slices to investigate the effects of propofol on the field excitatory postsynaptic potential (fEPSP), population spike, and epileptiform activity induced by a Mg(2+)-free condition. Propofol depressed the population spike, fEPSP, and epileptiform activity. Both aminophylline, a nonselective adenosine receptor antagonist, and 8-cyclopentyl-1,3-dipropylxanthine, an A(1) receptor antagonist, significantly reduced the effect of propofol on fEPSP amplitude. However, 3,7-dimethyl-1-propagylxanthine, an A(2) receptor antagonist, did not alter the effect of propofol on fEPSP amplitude. Picrotoxin, a specific chloride channel blocker, partly reduced the effect of propofol on epileptiform activity, but bicuculline, a competitive gamma-aminobutyric acid(A) receptor antagonist, failed to antagonize it. Aminophylline significantly reduced the action of propofol on the epileptiform activity. The anticonvulsant action of propofol was partly reduced by 8-cyclopentyl-1,3-dipropylxanthine, whereas 3,7-dimethyl-1-propagylxanthine failed to affect it. Adenosine depressed the amplitude of fEPSPs in a dose-dependent manner, and propofol enhanced this inhibition. The results demonstrated that, in rat hippocampal slices, propofol inhibits epileptiform activity. In addition, adenosine neuromodulation through the A(1) receptor may contribute to the anticonvulsant action of propofol.

Adenosine↗
PubMed2002

Modulation of lateral perforant path excitatory responses by metabotropic glutamate 8 (mGlu8) receptors.

The contribution of metabotropic glutamate 8 (mGlu8) receptors to modulation of medial and lateral perforant path (MPP and LPP) inputs to the dentate gyrus was investigated using electrophysiological recording of field excitatory postsynaptic potentials (fEPSPs) from hippocampal slices taken from wild-type and mGlu8 receptor knockout animals. Application of the selective group III mGlu receptor agonist, L-AP4 (1-100 microM), reduced fEPSPs evoked by LPP, but not MPP stimulation in wild-type slices in a concentration-dependent manner (EC(50) = 4.7 microM). The selective mGlu8 receptor agonist, DCPG (1-30 microM) also suppressed LPP fEPSPs with an EC(50) value of 3.1 microM. The L-AP4-induced reduction in LPP fEPSPs could be blocked by the group III antagonist, MSOP (100 microM) in wild-type slices and was eliminated in mGlu8 receptor-deficient slices. Additional experiments showed that MPP fEPSPs were suppressed by the group II agonist, LY379268 (0.01-3 microM) in control slices (EC(50) = 153.1 nM); an effect that was not altered in mGlu8 receptor knockout slices (EC(50) = 153.8 nM). In addition, LY379268 had little effect on fEPSPs evoked by LPP stimulation in mGlu8 receptor-deficient slices. In conjunction with recent receptor localization studies, these results suggest that the mGlu8 receptors serve as autoreceptors on LPP afferents to the dentate gyrus.

Animals↗
PubMed2006

Presynaptic GABA(B) receptors on glutamatergic terminals of CA1 pyramidal cells decrease in efficacy after partial hippocampal kindling.

We tested the hypothesis that presynaptic GABA(B) receptors on glutamatergic terminals (GABA(B) heterosynaptic receptors) decreased in efficacy after partial hippocampal kindling. Rats were implanted with chronically indwelling electrodes and 15 hippocampal afterdischarges were evoked by high-frequency electrical stimulation of hippocampal CA1. Control rats were implanted with electrodes but not given high-frequency stimulations. One to 21 days after the last afterdischarge, excitatory postsynaptic potentials (EPSPs) were recorded in CA1 of hippocampal slices in vitro, following stimulation of the stratum radiatum. Field EPSPs (fEPSPs) were recorded in CA1 stratum radiatum and intracellular EPSPs (iEPSPs) were recorded from CA1 pyramidal cells. GABA(B) receptor agonist +/- baclofen (10 microM) in the bath suppressed the fEPSPs significantly more in control than kindled rats, at 1 or 21 days after kindling. Similarly, baclofen (10 microM) suppressed iEPSPs more in the control than the kindled group of neurons recorded at 1 day after kindling. Suppression of the fEPSPs by 1 microM N(6)-cyclopentyladenosine, which acted on presynaptic A1 receptors, was not different between kindled and control rats. Activation of the GABA(B) heteroreceptors by a conditioning burst stimulation of CA3 afferents suppressed the iEPSPs evoked by a test pulse. The suppression of the iEPSPs at 250-500 ms condition-test interval was larger in control than kindled groups of neurons. It was concluded that the efficacy of presynaptic GABA(B) receptors on the glutamatergic terminals was reduced after partial hippocampal kindling. The reduction in heterosynaptic presynaptic GABA(B) receptor efficacy will increase glutamate release and seizure susceptibility, particularly during repeated neural activity.

Adenosine↗
PubMed1999

Role of GABAB receptor-mediated inhibition in reciprocal interareal pathways of rat visual cortex.

In neocortex, synaptic inhibition is mediated by gamma-aminobutyric acid-A (GABAA) and GABAB receptors. By using intracellular and patch-clamp recordings in slices of rat visual cortex we studied the balance of excitation and inhibition in different intracortical pathways. The study was focused on the strength of fast GABAA- and slow GABAB-mediated inhibition in interareal forward and feedback connections between area 17 and the secondary, latero-medial visual area (LM). Our results demonstrate that in most layer 2/3 neurons forward inputs elicited excitatory postsynaptic potentials (EPSPs) that were followed by fast GABAA- and slow GABAB-mediated hyperpolarizing inhibitory postsynaptic potentials (IPSPs). These responses resembled those elicited by horizontal connections within area 17 and those evoked by stimulation of the layer 6/white matter border. In contrast, in the feedback pathway hyperpolarizing fast and slow IPSPs were rare. However weak fast and slow IPSPs were unmasked by bath application of GABAB receptor antagonists. Because in the feedback pathway disynaptic fast and slow IPSPs were rare, polysynaptic EPSPs were more frequent than in forward, horizontal, and interlaminar circuits and were activated over a broader stimulus range. In addition, in the feedback pathway large-amplitude polysynaptic EPSPs were longer lasting and showed a late component whose onset coincided with that of slow IPSPs. In the forward pathway these late EPSPs were only seen with stimulus intensities that were below the activation threshold of slow IPSPs. Unlike strong forward inputs, feedback stimuli of a wide range of intensities increased the rate of ongoing neuronal firing. Thus, when forward and feedback inputs are simultaneously active, feedback inputs may provide late polysynaptic excitation that can offset slow IPSPs evoked by forward inputs and in turn may promote recurrent excitation through local intracolumnar circuits. This may provide a mechanism by which feedback inputs from higher cortical areas can amplify afferent signals in lower areas.

Animals↗
PubMed2004

Somatosensory corticothalamic projections: distinguishing drivers from modulators.

We used a juvenile mouse thalamocortical slice preparation with whole cell recording to investigate synaptic properties of corticothalamic inputs from somatosensory cortex to the ventral posterior medial and posterior medial nuclei (98 cells). We compared these data to those obtained from activating retinal and cortical inputs to the lateral geniculate nucleus (8 cells), the former representing a prototypical driver input and the latter, a typical modulator. Retinogeniculate activation evoked large, all-or-none excitatory postsynaptic potentials (EPSPs) that showed paired-pulse depression antagonized by N-methyl-d-aspartate (NMDA) and AMPA receptor blockers but with no sign of a metabotropic glutamate receptor (mGluR) component. Corticogeniculate activation evoked small, graded EPSPs showing paired-pulse facilitation, and the EPSPs showed both NMDA and AMPA receptor component plus an mGluR1 component. In the somatosensory thalamic relays, cortical stimulation elicited glutamatergic EPSPs in all thalamic cells, and these EPSPs fell into two groups. One, elicited from cortical layer 6 to cells of both nuclei, involved small, graded EPSPs with paired-pulse facilitation, and most also showed an mGluR1 component. The other, elicited from layer 5 to cells only of the posterior medial nucleus, involved large, all-or-none EPSPs with paired-pulse depression, and none showed an mGluR component. By analogy with results from the lateral geniculate nucleus, we conclude that the input from layer 6 to both nuclei acts as a modulator but that the layer 5 input to the posterior medial nucleus serves as a driver. Our data extend a common organizing principle from first-order nuclei to higher-order thalamic relays and further implicate the latter in corticocortical communication.

Animals↗
PubMed2005

Chronic intermittent ethanol exposure enhances NMDA-receptor-mediated synaptic responses and NMDA receptor expression in hippocampal CA1 region.

In previous studies, we found that chronic intermittent ethanol (CIE) treatment-a model of ethanol consumption in which animals are exposed to and withdrawn from intoxicating levels of ethanol on a daily basis-produces neuroadaptive changes in hippocampal area CA1 excitatory synaptic transmission and plasticity. Synaptic responses mediated by N-methyl-D-aspartate (NMDA) receptors are known to be sensitive to ethanol and could play an important role in the neuroadaptive changes induced by CIE treatment. To address this issue, we compared electrophysiological recordings of pharmacologically isolated NMDA-receptor-mediated field excitatory postsynaptic potentials (fEPSPs) in the CA1 region of hippocampal slices prepared from control rats and rats exposed to 2 weeks of CIE treatment administered by vapor inhalation. We found that fEPSPs induced by NMDA receptor activation were unaltered in slices prepared shortly after cessation of CIE treatment (i.e., < or = 1 day of withdrawal from CIE). However, following 7 days of withdrawal from CIE treatment, NMDA-receptor-mediated fEPSPs were augmented relative to age-matched controls. Western blot analysis of NMDA receptor subunit expression showed that, at 7 days of withdrawal, the level of protein for NR2A and NR2B subunits was elevated in the CA1 region of hippocampal slices from CIE-treated animals compared with slices from age-matched controls. These results are consistent with an involvement of NMDA-receptor-mediated synaptic responses in the neuroadaptive effects of CIE on hippocampal physiology and suggest that such changes may contribute to ethanol-induced changes in processes dependent on NMDA-receptor-mediated synaptic responses such as learning and memory, neural development, hyperexcitability and seizures, and neurotoxicity.

Animals↗
PubMed2004

A new cytochemical method for ultrastructural localization of Co2+ in rat hippocampal CA1 pyramidal neurons in vitro.

This paper describes new cytochemical method for the ultrastructural localization of Co(2+) following blockade of synaptic transmission. In the CA1 region of rat hippocampal slices, electrical stimulation of the Schaffer collaterals elicited field excitatory postsynaptic potentials (fEPSPs). The fEPSPs were completely blocked within 2 min after the addition of Co(2+) (2 mM). The slice was then fixed and precipitated Co(2+) was examined by means of a solution containing 2.5% glutaraldehyde and 10 mM K(3)[Fe(3+)(CN)(6)] in 90 mM NaCl. Electron spectroscopic imaging confirmed Co in the precipitate. The precipitates were found as clusters on the membranes of the fine apical dendrites and their spine heads of CA1 pyramidal neurons. No clustered precipitate was found when slices were treated: (1) without Co(2+); (2) after recovery from the Co(2+)-induced blockade of fEPSPs; (3) without electrical stimulation of the Schaffer collaterals; and (4) with dl-2-amino-5-phosphonopentanoate and 6-cyano-7-nitroquinoxaline-2,3-dione. After administrating glutamate (5 mM) in the presence of tetrodotoxin (1 microM) and Co(2+), precipitates were found on dendritic membranes and spine heads. These results indicate that the Schaffer collaterals stimulation induces the binding of Co(2+) on CA1 pyramidal neuron membrane.

2-Amino-5-phosphonovalerate↗
PubMed2001

Operant conditioning of rat H-reflex: effects on mean latency and duration.

We are currently studying the mechanisms of operantly conditioned changes in the H-reflex in the rat. Primate data suggest that H-reflex decrease is due to a positive shift in motoneuron firing threshold and a small decrease in the monosynaptic excitatory postsynaptic potential (EPSP), and that increase might be due to change in group-I oligosynaptic (especially disynaptic) input. To further evaluate the possibility of conditioned change in oligosynaptic input, we compared the mean latency (i.e., the average latency of the entire H-reflex) and the duration of control (i.e., pre-conditioning) H-reflexes with those of H-reflexes after up-conditioning or down-conditioning. Up-conditioning was associated with small, statistically significant increases in H-reflex mean latency [+0.11+/-0.05 (+/-SE) ms] and duration (+0.32+/-0.16 ms). The mean latency of the H-reflex increase (i.e., the part added to the H-reflex by up-conditioning) was 0.28+/-0.14 (+/-SE) ms greater than that of the control H-reflex. Down-conditioning had no significant effect on mean latency or duration. While these results indicate that operant conditioning does not greatly change H-reflex mean latency or duration, the effects detected with up-conditioning are consistent with the hypothesis that decreased inhibition, or increased excitation, by homonymous and heteronymous group-I oligosynaptic input contributes to the H-reflex increase produced by up-conditioning. Several other mechanisms might also account for these small effects.

Animals↗
PubMed2001

Potentially epileptogenic dysfunction of cortical NMDA- and GABA-mediated neurotransmission in Otx1-/- mice.

Knockout Otx1 mice present a microcephalic phenotype mainly due to reduced deep neocortical layers and spontaneous recurrent seizures. We investigated the excitable properties of layer V pyramidal neurons in neocortical slices prepared from Otx1-/- mice and age-matched controls. The qualitative firing properties of the neurons of Otx1-/- mice were identical to those found in wild-type controls, but the proportion of intrinsically bursting (IB) neurons was significantly smaller. This is in line with the lack of the Otx1 gene contribution to the generation and differentiation of neurons destined for the deep neocortical layers, in which IB neurons are located selectively in wild-type rodents. The pyramidal neurons recorded in Otx1-/- mice responded to near-threshold electrical stimulation of the underlying white matter, with aberrant polysynaptic excitatory potentials often leading to late action potential generation. When the strength of the stimulus was increased, the great majority of the Otx1-/- neurons (78%) responded with a prominent biphasic inhibitory postsynaptic potential that was significantly larger than that observed in the wild-type mice, and was often followed by complex postinhibitory depolarizing events. Both late excitatory postsynaptic potentials and postinhibitory excitation were selectively suppressed by NMDA receptor antagonists, but not by AMPA antagonists. We conclude that the cortical abnormalities of Otx1-/- neocortex due to a selective loss of large projecting neurons lead to a complex rearrangement of local circuitry, which is characterized by an excess of N-methyl-d-aspartate-mediated polysynaptic excitation that is counteracted by GABA-mediated inhibition in only a limited range of stimulus intensity. Prominent postsynaptic inhibitory potentials may also act as a further pro-epileptogenic event by synchronizing abnormal excitatory potentials.

2-Amino-5-phosphonovalerate↗
PubMed2006

Modulation of isolated N-methyl-d-aspartate receptor response under hyperbaric conditions.

In humans, hyperbaric pressure induces the high-pressure neurological syndrome (HPNS). HPNS is characterized by tremor, sleep disorders, electroencephalographic changes, and impairment of cognitive and motor performances. In animals, higher pressures result in convulsions and death. An increased N-methyl-d-aspartate receptor (NMDAR) response has been implicated with HPNS. We studied high-pressure effects on pharmacologically isolated NMDAR field excitatory postsynaptic potentials (fEPSPs). Hippocampal coronal brain slices from male Sprague-Dawley rats were prepared, constantly superfused with physiological solutions, gas-saturated at normobaric pressure and compressed up to 10.1 MPa with helium. fEPSPs were recorded from the dendritic layer of CA1 pyramidal neurones. High pressure significantly increased the single fEPSP delay, maximal initial slope, amplitude, decay time and time integral (elevated Na(+) and Ca(2+) influx) despite the known general decrease in glutamatergic synaptic release. The estimated negative and positive activation volumes (DeltaV*) for various kinetic segments of the fEPSP suggest a complex response of the receptor to pressure. The NMDAR frequency response was tested by a train of five stimuli. At 50-100 Hz, high pressure did not increase the fEPSPs' frequency-dependent depression and the train's time integral remained unchanged. At 25 Hz, pressure induced a larger frequency-dependent depression and significantly increased the time integral. Our results provide, for the first time, direct information on the isolated brain NMDAR response under hyperbaric conditions. These observations may explain some increase in the excitability of single normal glutametergic fEPSPs and their frequency responses.

Animals↗
PubMed1999

DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists.

We have used extracellular microelectrode recording to characterise a form of long-term depression (LTD) of synaptic transmission that can be induced by metabotropic glutamate (mGlu) receptor activation in the CA1 region of the young (12-18 day old) rat hippocampus. Activation of group I mGlu receptors by the specific agonist 3,5-dihydroxyphenylglyine (DHPG) induced LTD of field excitatory postsynaptic potentials (fEPSPs). The mGlu5 selective agonist 2-chloro-5-hydroxyphenylglycine was also capable of inducing LTD. In contrast, the group II specific agonist DCG-IV had no effect on synaptic transmission, whilst the group III receptor agonist (S)-2-amino-4-phosphonobutyrate elicited a depression that reversed fully upon agonist washout. DHPG-induced LTD could still be generated after prior saturation of electrically-induced NMDA receptor-dependent LTD. DHPG-induced LTD was reversed by tetanic stimulation comprising 100 shocks delivered at 100 Hz. A novel mGlu receptor antagonist, (RS)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) (LY393053) that potently inhibits mGlu1 and mGlu5 receptors, prevented the induction of DHPG-induced LTD. Like other mGlu receptor antagonists, LY393053 also reversed pre-established DHPG-induced LTD. In contrast, a potent mGlu1 selective antagonist (S)-2-methyl-4-carboxyphenylglycine (LY367385) did not prevent the induction of DHPG-induced LTD. In conclusion, DHPG, probably via activation of mGlu5 receptors, is able to induce a robust form of LTD in the CA1 region of the young rat hippocampus that is mechanistically distinct from NMDA receptor-dependent homosynaptic LTD.

Animals↗
PubMed2000

Development of NMDA and non-NMDA receptor-mediated excitatory synaptic transmission in geniculocortical and corticocortical connections in organotypic coculture preparations.

Development of N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated excitatory synaptic transmission was studied in the visual cortex using organotypic slice cocultures. A slice of visual cortex (VC) dissected from newborn rats was cocultured with either a chunk of embryonic lateral geniculate nucleus (LGN) or another VC. During 7-38 days in vitro (DIV), geniculocortical monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded from layer IV neurons in response to stimulation of the LGN in cocultures of the VC with the LGN. Similarly, corticocortical monosynaptic EPSPs were recorded from layers II/III and V/VI neurons in cocultures of two VCs when stimulating the partner VC. The initial slopes of the non-NMDA and NMDA receptor-mediated components of the EPSPs, which were dissociated pharmacologically, were assessed and compared among three different culture stages, early (7-11 DIV), middle (12-15 DIV) and late (17-38 DIV). With progression of the culture stage, the non-NMDA component tended to increase in both the geniculocortical and corticocortical connections. In contrast, the NMDA component exhibited distinct developmental changes. The NMDA component in layer IV neurons, which receive geniculate inputs, showed a transient increase in the middle stage. In the corticocortical connection, the magnitude of the NMDA component was large in the early stage and maintained through all culture stages in layer V/VI cells, whereas in layer II/III cells it decreased sharply by the late stage. Our results suggest that glutamatergic transmission in the visual cortex develops differently in the geniculocortical and corticocortical connections.

2-Amino-5-phosphonovalerate↗
PubMed2002

Blockade of neuropeptide Y(2) receptors and suppression of NPY's anti-epileptic actions in the rat hippocampal slice by BIIE0246.

Neuropeptide Y (NPY) has been shown to suppress synaptic excitation in rat hippocampus by a presynaptic action. The Y(2) (Y(2)R) and the Y(5) (Y(5)R) receptors have both been implicated in this action. We used the non-peptide, Y(2)R-selective antagonist, BIIE0246, to test the hypothesis that the Y(2)R mediates both the presynaptic inhibitory and anti-epileptic actions of NPY in rat hippocampus in vitro. NPY and the Y(2)R-selective agonist, [ahx(5-24)]NPY, both inhibited the population excitatory postsynaptic potential (pEPSP) evoked in area CA1 by stratum radiatum stimulation in a concentration-dependent manner. BIIE0246 suppressed the inhibitory effects of both agonists, suppressing the maximal inhibition without causing a change in the agonist EC(50), in a manner inconsistent with competitive antagonism. BIIE0246 washed out from hippocampal slices extremely slowly. Application of agonist at high concentrations (1 - 3 microM) for prolonged periods did not alter the rate of washout, but did partially overcome the antagonism, inconsistent with an insurmountable antagonism by BIIE0246. In the stimulus train-induced bursting (STIB) model of ictal activity in hippocampal slices, both NPY and [ahx(5-24)]NPY inhibited primary afterdischarge (1 degrees AD) activity. BIIE0246 (100 nM) completely suppressed the actions of NPY and [ahx(5-24)]NPY in this model. In contrast, the potent Y(5)R-selective agonist, Ala(31)Aib(32)NPY, affected neither 1 degrees AD activity in the presence of BIIE0246, nor, by itself, even the pEPSP in CA1. BIIE0246 potently suppresses NPY actions in rat hippocampus, suggesting a dominant role for Y(2)R there. The apparently insurmountable antagonism observed may result from the lipophilic nature of the antagonist.

Animals↗
PubMed1985

Spontaneous electrical activity induced by herpes virus infection in rat sensory neuron cultures.

Dissociated cultures of rat dorsal root ganglion neurons were infected with a syncytial strain of herpes simplex virus type 1. Over 90% of neurons in infected cultures were spontaneously active and fired action potentials which, on membrane potential hyperpolarization, were replaced by depolarizing events similar to excitatory postsynaptic potentials. Amplitude analysis of these events produced populations described by the sum of several unitary events with Gaussian rather than binomial or Poisson distributions. Such spontaneous activity was blocked by tetrodotoxin but not by low calcium high magnesium solutions containing cadmium. Simultaneous recording from pairs of spontaneously active neurons revealed excitatory connexions between cells. It is suggested that virus-induced fusion of nerve cell processes induces electrical coupling between sensory neurons, and that the resulting electrical network supports spontaneous activity.

Animals↗
PubMed2000

Site independence of EPSP time course is mediated by dendritic I(h) in neocortical pyramidal neurons.

Neocortical layer 5 pyramidal neurons possess long apical dendrites that receive a significant portion of the neurons excitatory synaptic input. Passive neuronal models indicate that the time course of excitatory postsynaptic potentials (EPSPs) generated in the apical dendrite will be prolonged as they propagate toward the soma. EPSP propagation may, however, be influenced by the recruitment of dendritic voltage-activated channels. Here we investigate the properties and distribution of I(h) channels in the axon, soma, and apical dendrites of neocortical layer 5 pyramidal neurons, and their effect on EPSP time course. We find a linear increase (9 pA/100 microm) in the density of dendritic I(h) channels with distance from soma. This nonuniform distribution of I(h) channels generates site independence of EPSP time course, such that the half-width at the soma of distally generated EPSPs (up to 435 microm from soma) was similar to somatically generated EPSPs. As a corollary, a normalization of temporal summation of EPSPs was observed. The site independence of somatic EPSP time course was found to collapse after pharmacological blockade of I(h) channels, revealing pronounced temporal summation of distally generated EPSPs, which could be further enhanced by TTX-sensitive sodium channels. These data indicate that an increasing density of apical dendritic I(h) channels mitigates the influence of cable filtering on somatic EPSP time course and temporal summation in neocortical layer 5 pyramidal neurons.

Animals↗