Biomedical subjects

Y Sahara

Publications and source records attributed to Y Sahara.

At least 19 recordsLinked to original sources

PubMed2001

Cellular localization of metabotropic glutamate receptors mGluR1, 2/3, 5 and 7 in the main and accessory olfactory bulb of the rat.

The cellular localization of metabotropic glutamate receptors (mGluRs) (mGluR1alpha, 2/3, 5a and 7) in the main and accessory olfactory bulb (MOB and AOB) of adult rats was compared by using affinity purified polyclonal antibodies directed to their C-termini. mGluR1alpha and mGluR5a immunoreactivities were located in comparable structures of the MOB and AOB with different levels of intensity. mGluR5a reactivity was high in the AOB. mGluR2/3 showed a different pattern of expression in the MOB compared to that observed in the AOB; the periglomerular region of the MOB was strongly stained, but in the AOB it was the mitral/tufted cell layer that was intense. The mitral cell bodies in the MOB were strongly immunoreactive for mGluR7. These differences in the distribution of mGluRs in the MOB and AOB may reflect differences in synaptic transmission and sensitivity to neuromodulation in the two systems.

Amino Acid Sequence↗

PubMed2001

Quantal components of the excitatory postsynaptic currents at a rat central auditory synapse.

1. Paired whole-cell recordings were made from a glutamatergic giant nerve terminal, the calyx of Held, and its postsynaptic target cell in the medial nucleus of the trapezoid body (MNTB) in the brainstem slice of juvenile rat. Excitatory postsynaptic currents (EPSCs) were evoked by presynaptic action potentials triggered by brief (1 ms) depolarizing pulses. 2. In normal artificial cerebrospinal fluid (ACSF), EPSCs of several nanoamperes in amplitude were evoked at a relatively constant latency with no failure, whereas in low [Ca(2+)](o)-high [Mg(2+)](o) solutions, EPSCs fluctuated both in amplitude and latency, and stochastic failures of transmitter release were observed in response to presynaptic action potentials. 3. After blocking action potentials with tetrodotoxin (TTX), direct depolarization of the calyceal preterminal elicited asynchronous release of miniature EPSCs (mEPSCs). When the magnitude of depolarization was increased, mEPSCs increased in frequency. Being consistent with their quantal nature, their mean amplitude remained constant over a wide range of frequencies. The amplitude distribution of mEPSCs was slightly skewed (skewness = 1.06), with a mean conductance of 0.45 nS and a coefficient of variation (c.v.) of 0.43. 4. Single-channel conductance underlying mEPSCs was estimated using non-stationary fluctuation analysis. The weighted mean single channel conductance was 20.4 pS, suggesting that a single quantum opens 22 postsynaptic glutamate receptor channels on average. 5. After washing out TTX, EPSCs evoked by presynaptic action potentials were tested for quantal analysis based upon the mean amplitude of mEPSCs and their variance. In low [Ca(2+)](o)-high [Mg(2+)](o) solutions, quantal contents estimated from the EPSC/mEPSC ratio, rate of failures or c.v. assuming Poisson's statistics, coincided with each other. Evoked EPSCs could be fitted by integer multiples of mEPSCs with an assumption of incremental variance more adequately than the constant variance assumption. 6. It is concluded that the rat central auditory synaptic transmission is made in a quantal manner as at the frog neuromuscular junction.

Action Potentials↗

PubMed2001

Microscopic kinetics and energetics distinguish GABA(A) receptor agonists from antagonists.

Although agonists and competitive antagonists presumably occupy overlapping binding sites on ligand-gated channels, these interactions cannot be identical because agonists cause channel opening whereas antagonists do not. One explanation is that only agonist binding performs enough work on the receptor to cause the conformational changes that lead to gating. This idea is supported by agonist binding rates at GABA(A) and nicotinic acetylcholine receptors that are slower than expected for a diffusion-limited process, suggesting that agonist binding involves an energy-requiring event. This hypothesis predicts that competitive antagonist binding should require less activation energy than agonist binding. To test this idea, we developed a novel deconvolution-based method to compare binding and unbinding kinetics of GABA(A) receptor agonists and antagonists in outside-out patches from rat hippocampal neurons. Agonist and antagonist unbinding rates were steeply correlated with affinity. Unlike the agonists, three of the four antagonists tested had binding rates that were fast, independent of affinity, and could be accounted for by diffusion- and dehydration-limited processes. In contrast, agonist binding involved additional energy-requiring steps, consistent with the idea that channel gating is initiated by agonist-triggered movements within the ligand binding site. Antagonist binding does not appear to produce such movements, and may in fact prevent them.

Animals↗

PubMed2001

Recurrence of a neurenteric cyst with malignant transformation in the foramen magnum after total resection. Case report.

A 53-year-old man presented with recurrence of a neurenteric cyst with malignant transformation in the foramen magnum 3.5 years after total resection of the original tumor had been reported. For 2 years following the initial surgery, the patient had been in good condition, but then underwent ventriculoperitoneal shunt placement for intracranial hypertension. At the time there was no evidence of recurrence of the tumor on magnetic resonance (MR) images. One and one-half years later, he presented with headache and anorexia. A massive recurrent tumor was identified on MR images. The tumor was severely adhesive to the brainstem, cranial nerves, and vessels, allowing only partial resection. Histological examination of tumor specimens obtained during the first and second craniotomies indicated a malignant change from a typical neurenteric cyst with a one-layer epithelium in the first specimen to an adenocarcinoma with papillary proliferation in the second. The results of various immunohistochemical studies of the first specimen were typical of those of a neurenteric cyst. The second specimen displayed stronger staining of carbohydrate 19-9 and carcinoembryonic antigens than the initial specimen. The percentage of Ki-67 antigen (MIB-1)-positive cells increased from 0% in the first specimen to 6.7% in the second. To the authors' knowledge this is the first case in which malignant transformation has been demonstrated after total resection of a neurenteric cyst in the foramen magnum.

Adenocarcinoma, Papillary↗

PubMed2000

A new class of neurotoxin from wasp venom slows inactivation of sodium current.

The effects of alpha-pompilidotoxin (alpha-PMTX), a new neurotoxin isolated from the venom of a solitary wasp, were studied on the neuromuscular synapses in lobster walking leg and the rat trigeminal ganglion (TG) neurons. Paired intracellular recordings from the presynaptic axon terminals and the innervating lobster leg muscles revealed that alpha-PMTX induced long bursts of action potentials in the presynaptic axon, which resulted in facilitated excitatory and inhibitory synaptic transmission. The action of alpha-PMTX was distinct from that of other known facilitatory presynaptic toxins, including sea anemone toxins and alpha-scorpion toxins, which modify the fast inactivation of Na+ current. We further characterized the action of alpha-PMTX on Na+ channels by whole-cell recordings from rat trigeminal neurons. We found that alpha-PMTX slowed the Na+ channels inactivation process without changing the peak current-voltage relationship or the activation time course of tetrodotoxin (TTX)-sensitive Na+ currents, and that alpha-PMTX had voltage-dependent effects on the rate of recovery from Na+ current inactivation and deactivating tail currents. The results suggest that alpha-PMTX slows or blocks conformational changes required for fast inactivation of the Na+ channels on the extracellular surface. The simple structure of alpha-PMTX, consisting of 13 amino acids, would be advantageous for understanding the functional architecture of Na+ channel protein.

4-Aminopyridine↗

PubMed1998

Defining affinity with the GABAA receptor.

At nicotinic and glutamatergic synapses, the duration of the postsynaptic response depends on the affinity of the receptor for transmitter (Colquhoun et al., 1977;Pan et al., 1993). Affinity is often thought to be determined by the ligand unbinding rate, whereas the binding rate is assumed to be diffusion-limited. In this view, the receptor selects for those ligands that form a stable complex on binding, but binding is uniformly fast and does not itself affect selectivity. We tested these assumptions for the GABAA receptor by dissecting the contributions of microscopic binding and unbinding kinetics for agonists of equal efficacy but of widely differing affinities. Agonist pulses applied to outside-out patches of cultured rat hippocampal neurons revealed that agonist unbinding rates could not account for affinity if diffusion-limited binding was assumed. However, direct measurement of the instantaneous competition between agonists and a competitive antagonist revealed that binding rates were orders of magnitude slower than expected for free diffusion, being more steeply correlated with affinity than were the unbinding rates. The deviation from diffusion-limited binding indicates that a ligand-specific energy barrier between the unbound and bound states determines GABAA receptor selectivity. This barrier and our kinetic observations can be quantitatively modeled by requiring the participation of movable elements within a flexible GABA binding site.

Animals↗

PubMed1998

Dendrodendritic inhibition in the olfactory bulb is driven by NMDA receptors.

At many central excitatory synapses, AMPA receptors relay the electrical signal, whereas activation of NMDA receptors is conditional and serves a modulatory function. We show here quite a different role for NMDA receptors at dendrodendritic synapses between mitral and granule cells in the rat olfactory bulb. In whole-cell patch-clamp recordings in bulb slices, stimulation of mitral cells elicited slowly decaying, GABAA receptor-mediated reciprocal IPSCs that reflected prolonged GABA release from granule cells. Although granule cells had a normal complement of AMPA and NMDA receptors, the IPSC was completely blocked by the NMDA receptor antagonist D,L-AP-5, suggesting that NMDA receptor activation is an absolute requirement for dendrodendritic inhibition. The AMPA receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxobenzo[f]quinoxaline-7-sulfonamide (NBQX) had no effect on IPSCs in the absence of extracellular magnesium but modestly reduced IPSCs in 1 mM magnesium, indicating that the primary effect of the AMPA receptor-mediated depolarization was to facilitate the unblocking of NMDA receptors. Granule cell voltage recordings indicated that effective spike stimulation in granule cells depended on the slow NMDA receptor kinetics. Granule cells also showed a pronounced delay between synaptic stimulation and action potential generation, suggesting that their intrinsic membrane properties underlie the ineffectiveness of brief AMPA receptor-mediated EPSPs. NMDA receptors also seem to have a central role in dendrodendritic inhibition in vivo, because intraperitoneal dizocilpine maleate (MK-801) injection in young adult rats resulted in disinhibition of mitral cells as measured by the generation of c-fos mRNA. The unique dependence of dendrodendritic inhibition on slow EPSPs generated by NMDA receptors suggests that olfactory information processing depends on long-lasting reciprocal and lateral inhibition.

2-Amino-5-phosphonovalerate↗

PubMed1998

Activation kinetics of AMPA receptor channels reveal the number of functional agonist binding sites.

AMPA and NMDA receptor channels are closely related molecules, yet they respond to glutamate with distinct kinetics, attributable to differences in ligand binding and channel gating steps (for review, see Edmonds et al., 1995). We used two complementary approaches to investigate the number of functional binding sites on AMPA channels on outside-out patches from cultured hippocampal neurons. The activation kinetics of agonist binding were measured during rapid steps into low concentrations of selective AMPA receptor agonists and during steps from a competitive AMPA receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione, into a saturating concentration of agonist. Both approaches revealed sigmoidal kinetics, which suggests that multiple agonist binding steps or antagonist unbinding steps are needed for channel activation. A kinetic model with two independent binding sites gave a better fit to the activation phase than models with one or three independent sites. A more refined analysis incorporating cooperative interaction between the two binding sites significantly improved the fits to the responses. The affinity of the first binding step was two to three times higher than the second step. These results demonstrate that binding of two agonist molecules are needed to activate AMPA receptors, but the two binding sites are not identical and independent. Because NMDA receptors require four ligand molecules for activation (two glycine and two glutamate; Benveniste and Mayer, 1991; Clements and Westbrook, 1991), it may be that some binding sites on AMPA receptors are functionally silent.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal ganglion neurons.

To determine the subunit composition of high-affinity kainate receptors in native neurons is a challenging problem because of the expression of more than one GluR subunit. In the present study the question of whether GluR5 and/or GluR6 subunits combine with KA-1 or KA-2 subunits in vivo is addressed by performing detailed physiological, pharmacological, and molecular characterization of functional kainate receptor channels in acutely dissociated trigeminal ganglion (TG) neurons. The results show that (1) smaller diameter TG neurons (<30 microm) respond to L-glutamate and kainate, and the currents gated by kainate desensitize with prolonged agonist exposure; (2) all kainate receptor subunits are detected to some extent by reverse transcriptase-PCR, whereas glutamate receptor subunits GluR5 and KA-2 are expressed at high levels in the TG; (3) there is an obvious similarity between the features of native kainate receptor channels in TG neurons and of heteromeric recombinant GluR5(R)/KA-2 channels in pharmacological properties, desensitization, rectification, ion permeability, and mean channel conductance; and (4) the age-dependent increase in GluR5 and KA-2 RNA levels in the TG is correlated well with an increased number of kainate-sensitive cells during postnatal development. Our data suggest that the heteromeric GluR5/KA2 combination actually occurs in TG neurons and give a clue as to the subunit composition of native kainate receptor channels.

Animals↗

PubMed1996

Hypoglossal premotor neurons in the rostral medullary parvocellular reticular formation participate in cortically-induced rhythmical tongue movements.

Premotor neurons projecting to the hypoglossal (XII) nucleus and participating in cortically-induced rhythmical tongue movements were defined by extracellular recording in the cat. Two thirds (37/57) of antidromically identified XII premotor neurons sampled in the rostral medullary parvocellular reticular formation showed changes in their firing pattern during cortically-induced rhythmical activity of XII motoneurons. Fifteen of the 37 neurons showed a firing in phase with rhythmical activity of either the medial or lateral branch of the XII nerve (phasic-type). The remaining 22 neurons showed an increase in discharge with no apparent correlation with cortically-induced rhythmical activity of the XII nerve (non-phasic-type). Among the phasic- and non-phasic-type neurons, 30 neurons received inputs from the cortical masticatory area, and 14 neurons received further excitatory inputs from the inferior alveolar nerve. By systematic mapping of the stimulation sites effective for antidromic activation, four phasic-type neurons were confirmed to project to either tongue-protruding or -retracting XII motoneuron pools in accordance with their burst firing, suggesting that the phasic-type premotor neurons contribute to excitation of XII motoneurons during cortically-induced rhythmical activity. It is concluded that there are the XII premotor neurons driving cortically-induced rhythmical activity of XII motoneurons in the rostral medullary parvocellular reticular formation.

Animals↗

PubMed1994

Estradiol transcriptionally and posttranscriptionally up-regulates thyrotropin-releasing hormone receptor messenger ribonucleic acid in rat pituitary cells.

17 beta-Estradiol (E2) has been shown to up-regulate the binding activity of the TRH receptor in rat pituitary cells. In this report, we investigated whether and how E2 alters TRH receptor expression at the mRNA level using the oocyte mRNA expression system, Northern blot analysis, and nuclear run-on assay. In oocytes injected with mRNA from the anterior pituitaries or GH3 cells, a TRH-induced 45Ca2+ efflux appeared. This efflux was dependent on the amount of TRH and injected RNA, and was inhibited by simultaneous addition of chloridazepoxide, an antagonist of the TRH receptor. Treatment of GH3 cells with E2 increased TRH receptor mRNA activity, as assessed in the oocyte expression system; the E2 effect became apparent after 3 h of treatment and reached a maximum (3- to 4-fold) between 6-72 h after addition. Northern blot analysis with a 412-basepair cDNA fragment or 3.7-kilobasepair full-length cDNA of the TRH receptor as a probe showed that E2 maximally (5-fold) increased the TRH receptor mRNA level of GH3 cells, with a half-maximal concentration of 0.1 nM after 6 h of treatment. The elevated level of mRNA induced by E2 was augmented, rather than impeded, by cycloheximide, indicating that ongoing protein synthesis was not required for the induction. The rate of transcription of the TRH receptor gene in isolated nuclei taken from GH3 cells was increased 3-fold by 2 h of treatment with E2. Furthermore, the half-life of the TRH receptor mRNA in GH3 cells was prolonged by E2 (from 2.3 to 4.4 h). These results demonstrate that E2 up-regulates the TRH receptors of the pituitary cells at the mRNA level by increasing both the transcription rate and stability.

Animals↗

PubMed1993

Modulation of calcium currents by a metabotropic glutamate receptor involves fast and slow kinetic components in cultured hippocampal neurons.

The modulation of high-threshold Ca2+ currents by the selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), was investigated in cultured hippocampal neurons using whole-cell voltage-clamp recording. ACPD reduced high-threshold Ca2+ currents carried by Ba2+ with an EC50 of 15.5 microM. The inhibition was reversible, voltage dependent, and blocked by L-2-amino-3-phosphonopropionic acid (1 mM) or by pretreatment with pertussis toxin. Inhibition by ACPD was greatly enhanced, and became irreversible, when the nonhydrolyzable GTP analog GTP gamma S was included in the whole-cell pipette. In some neurons, the Ba2+ current was inhibited by L(+)-2-amino-4-phosphonobutanoic acid (L-AP4) as well as ACPD while most cells were insensitive to L-AP4, suggesting that these agonists activate distinct receptors. The inhibition of Ca2+ currents was reduced but not eliminated in the presence of either omega-conotoxin GVIA or nifedipine, suggesting that both N- and L-type Ca2+ currents were affected. The degree and kinetics of inhibition were dependent on intracellular calcium. With [Ca]i < 1 nM, inhibition had a fast onset (t approximately 1-2 sec) and a rapid recovery, consistent with a membrane-delimited pathway. However, a slow component of inhibition appeared when the steady state [Ca]i was increased to 100 nM (t onset approximately 3 min). The slow component did not require transient Ca2+ influx or release of intracellular Ca2+. We suggest that Ca2+ channel modulation by ACPD involves either two mGluR subtypes with separate coupling mechanisms or a single mGluR that couples to both mechanisms.

Alanine↗

PubMed1991

A voltage-clamp study of the effects of Joro spider toxin and zinc on excitatory synaptic transmission in CA1 pyramidal cells of the guinea pig hippocampal slice.

Using the single-electrode voltage-clamp technique, we have examined the effects of a non-N-methyl-D-aspartate (NMDA) antagonist. Joro spider toxin (JSTX), and of an NMDA antagonist, zinc, on excitatory postsynaptic currents (EPSCs) evoked by stimulation of stratum radiatum in CA1 pyramidal cells of the guinea-pig hippocampal slice. Pressure application of a synthesized JSTX (JSTX-3) at 10-200 microM greatly reduced the EPSCs (14/19 cells). The block by JSTX-3 was observed in pyramidal cells where the EPSCs showed linear peak current-voltage (I-V) relations in the control. EPSCs remaining after JSTX-3 application showed non-linear peak I-V relationships (10/14 cells), and were blocked by puff application of the selective NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV) at 200 microM (6/10 cells). In the presence of JSTX-3, the decay time constant of the EPSC was increased and was less affected by membrane potential. JSTX-3 had no detectable effects on EPSCs apparently mediated solely by NMDA receptor. These observations suggest that JSTX-3 blocks excitatory synaptic transmission mainly by suppressing non-NMDA-receptor-mediated EPSCs, and that the JSTX-3-insensitive component is mediated at least in part by NMDA receptors in the hippocampal slice. Zinc (100-200 microM) reversibly attenuated EPSCs (6/9 cells) and appeared to block a slower component of the EPSCs, suggesting that mainly NMDA receptor-mediated currents were affected.

2-Amino-5-phosphonovalerate↗

PubMed1991

Nonstationary fluctuation analysis and direct resolution of single channel currents at postsynaptic sites.

In order to measure unitary properties of receptor channels at the postsynaptic site, the noise within the decay phases of inhibitory postsynaptic currents (IPSCs) and of N-methyl-D-aspartate (NMDA)-dependent excitatory postsynaptic currents (EPSCs) in rat hippocampal neurons was studied by nonstationary fluctuation analysis. Least squares scaling of the mean current was used to circumvent the wide variation in amplitude of postsynaptic currents. The variance of fluctuations around the expected current was analyzed to calculate single channel conductance, and fluctuation kinetics were studied with power spectra. The single channel conductance underlying the IPSC was measured as 14 pS, whereas that underlying the EPSC was 42 pS. Openings of the EPSC channel could also be resolved directly in low-noise whole-cell recordings, allowing verification of the accuracy of the fluctuation analysis. The results are the first measurements of the properties of single postsynaptic channels activated during synaptic currents, and suggest that the technique can be widely applicable in investigations of synaptic mechanism and plasticity.

2-Amino-5-phosphonovalerate↗

PubMed1991

Spider toxin and the glutamate receptors.

A neurotoxin (JSTX) was isolated from the venom of spider (Nephila clavata). JSTX blocked both the excitatory postsynaptic (EPSPs) and glutamate-induced potentials in lobster neuromuscular synapse and squid giant synapse. In mammalian central nervous system, JSTX blocked the EPSPs in CA1 pyramidal neurons resulting from stimulation of Schaffer collateral/commissure input. Pharmacological investigation showed that JSTX preferentially suppressed quisqualate/kainate receptor subtypes but was much less effective on NMDA receptor. Using synthesized spider toxins we studied the structure-activity relationship and found that the 2,4 dihydroxyphenylacetyl asparagine in the toxin structure was responsible for suppressive action, while the remaining part containing a polyamine was related to the agonist binding site with the polycationic part enhancing the toxic activity. Labeling of synthesized JSTX was used for histochemical as well as biochemical studies. Using autoradiography, 125I-JSTX-3 was found to bind at the lobster neuromuscular synapse. Histochemical study utilizing the interaction of biotinylated JSTX-3 with avidin showed specific binding of the toxin in rat cerebellum and hippocampus. JSTX-3-binding protein was purified from rat brain by affinity chromatography. SDS-PAGE of the affinity purified protein showed at least 4 bands ranging from 40 to 70 kDa.

Animals↗

PubMed1990

Intracellular records of the effects of primary afferent input in lumbar spinoreticular tract neurons in the cat.

1. The afferent-evoked synaptic input to lumbar spinal cord (L5-S1) neurons that were activated antidromically from the medial pontomedullary reticular formation (nucleus reticularis gigantocelluaris and vicinity) was investigated with the use of intracellular recordings in pentobarbital sodium-anesthetized cats. 2. Spinoreticular tract (SRT) neurons (n = 33) were categorized into three types ("deep-inhibited," "deep-complex," and "intermediate") on the basis of their locations and of their responses to natural and electrical stimulation. 3. The deep-inhibited-type neurons, located in the medial part of the deeper laminae (approximately VI-VIII), comprised a large component of the sample (20/33). They had no demonstrable excitatory receptive field (RF). However, electrical stimulation of low-threshold cutaneous afferents of hindlimb nerves evoked inhibitory postsynaptic potentials (IPSPs) via an oligosynaptic linkage. High-threshold cutaneous and muscle afferents also evoked IPSPs. 4. In the deep-complex-type neurons (8/33), electrical stimulation of low-threshold cutaneous afferents evoked complex IPSP-excitatory postsynaptic potential (EPSP) sequences. With intense stimuli, long-latency C-fiber-like EPSPs were evoked. Two of these eight neurons were characterized as wide-dynamic-range (WDR) neurons with large, excitatory and inhibitory cutaneous RFs. 5. Intermediate-type neurons (5/33) were concentrated in the lateral spinal gray and relatively superficially (approximately lamina V). These neurons had convergent low- and high-threshold cutaneous inputs (WDR neurons). Electrical stimulation of low-threshold cutaneous afferent fibers from within the excitatory RF evoked mono- or disynaptic EPSPs followed by IPSPs. High-threshold muscle and cutaneous afferents also evoked EPSPs. 6. These results show that SRT neurons have a variety of response characteristics resulting from various degrees of spatial and temporal summation of primary afferent input. Neurons with widespread inhibitory responses but no excitatory drive from the periphery comprise a surprisingly large component of the SRT: the function of these cells is unknown. It is apparent that the spinoreticular projection has considerable functional heterogeneity.

Animals↗

PubMed1989

Effects of a spider toxin (JSTX) on hippocampal CA1 neurons in vitro.

The effect of a toxin (JSTX) obtained from Nephila clavata (Joro spider) on the CA1 pyramidal neurons of the hippocampus was studied using slice preparations. JSTX blocked the excitatory postsynaptic potentials (EPSPs) in the pyramidal neuron evoked by Schaffer collateral stimulation but was without effect on the antidromic action potentials or on the resting conductance. Depolarization induced by ionophoretic application of glutamate was readily suppressed by JSTX but aspartate-induced depolarization was much less sensitive to the toxin. Among preferential agonists activating 3 receptor subtypes for excitatory amino acids, quisqualate responses were most effectively suppressed by JSTX. Kainate responses were similarly suppressed but in some cells higher concentration of the toxin was needed to block the responses. N-methyl-D-aspartate (NMDA) responses were the least sensitive to JSTX but they were suppressed by +/- 2-amino-5-phosphonovaleric acid (APV). Long term potentiation (LTP) once it had taken place was not completely inhibited by APV. In the presence of JSTX, however, LTP was blocked and tetanic stimuli produced only a short-lived potentiation. In Mg2+ free solution, an orthodromic stimulation evoked repetitive spike responses which were superimposed on the depolarization following the initial spike. APV suppressed the depolarization and associated spikes leaving an orthodromic response which was sensitive to JSTX. The results suggest that JSTX blocks EPSPs in CA1 pyramidal neurons which are mediated by non-NMDA type receptors.

Action Potentials↗

PubMed1988

Synaptic bases of cortically-induced rhythmical hypoglossal motoneuronal activity in the cat.

Intracellular recordings were made from hypoglossal motoneurons during cortically-induced fictive mastication in paralyzed encéphale isolé cats. Repetitive stimulation of the masticatory area of the cerebral cortex induced rhythmical tongue movements coordinated with jaw movements. After the animal was immobilized, the cortical stimulation still induced rhythmical burst activity in the hypoglossal nerve and the digastric nerve. The burst activities in the medial and lateral branches of the hypoglossal nerve alternated rhythmically, and were in and out of phase with the burst activities of the digastric nerve, respectively. All hypoglossal motoneurons showed rhythmical intracellular potentials during repetitive cortical stimulation. The rhythmical depolarizing potentials superimposed by spike bursts appeared in phase with rhythmical bursts in either the lateral or medial branch of the hypoglossal nerve. No hyperpolarization was present between consecutive depolarizing potentials. Synaptic activation noise increased coincidentally with the depolarizing potential, indicating that EPSPs were involved in the generation of the depolarizing potential. No evidence was obtained for the existence of IPSPs during the inter-depolarizing phase by intracellular current injection. It was concluded that rhythmical bombardment of excitatory impulses to hypoglossal motoneurons was responsible for the rhythmical activity induced by repetitive stimulation of the cortical masticatory area.

Animals↗