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PubMed2000

Backpropagation of the delta oscillation and the retinal excitatory postsynaptic potential in a multi-compartment model of thalamocortical neurons.

Uniform and non-uniform somato-dendritic distributions of the ion channels carrying the low-threshold Ca(2+) current (I(T)), the hyperpolarization-activated inward current (I(h)), the fast Na(+) current (I(Na)) and the delayed rectifier current (I(K)) were investigated in a multi-compartment model of a thalamocortical neuron for their suitability to reproduce the delta oscillation and the retinal excitatory post-synaptic potential recorded in vitro from the soma of thalamocortical neurons. The backpropagation of these simulated activities along the dendritic tree was also studied. A uniform somato-dendritic distribution of the maximal conductance of I(T) and I(K) (g(T) and g(K), respectively) was sufficient to simulate with acceptable accuracy: (i) the delta oscillation, and its phase resetting by somatically injected current pulses; as well as (ii) the retinal excitatory postsynaptic potential, and its alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate and/or N-methyl-D-aspartate components. In addition, simulations where the dendritic g(T) and g(K) were either reduced (both by up to 34%) or increased (both by up to 15%) of their respective value on the soma still admitted a successful reproduction of the experimental activity. When the dendritic distributions were non-uniform, models where the proximal and distal dendritic g(T) was up to 1.8- and 1. 2-fold larger, respectively, than g(T(s)) produced accurate simulations of the delta oscillation (and its phase resetting curves) as well as the synaptic potentials without need of a concomitant increase in proximal or distal dendritic g(K). Furthermore, an increase in proximal dendritic g(T) and g(K) of up to fourfold their respective value on the soma resulted in acceptable simulation results. Addition of dendritic Na(+) channels to the uniformly or non-uniformly distributed somato-dendritic T-type Ca(2+) and K(+) channels did not further improve the overall qualitative and quantitative accuracy of the simulations, except for increasing the number of action potentials in bursts elicited by low-threshold Ca(2+) potentials. Dendritic I(h) failed to produce a marked effect on the simulated delta oscillation and the excitatory postsynaptic potential. In the presence of uniform and non-uniform dendritic g(T) and g(K), the delta oscillation propagated from the soma to the distal dendrites with no change in frequency and voltage-dependence, though the dendritic action potential amplitude was gradually reduced towards the distal dendrites. The amplitude and rising time of the simulated retinal excitatory postsynaptic potential were only slightly decreased during their propagation from their proximal dendritic site of origin to the soma or the distal dendrites. These results indicate that a multi-compartment model with passive dendrites cannot fully reproduce the experimental activity of thalamocortical neurons, while both uniform and non-uniform somato-dendritic g(T) and g(K) distributions are compatible with the properties of the delta oscillation and the retinal excitatory postsynaptic potential recorded in vitro from the soma of these neurons. Furthermore, by predicting the existence of backpropagation of low-threshold Ca(2+) potentials and retinal postsynaptic potentials up to the distal dendrites, our findings suggest a putative role for the delta oscillation in the dendritic processing of neuronal activity, and support previous hypotheses on the interaction between retinal and cortical excitatory postsynaptic potentials on thalamocortical neuron dendrites.

Action Potentials↗

PubMed1996

N-methyl-D-aspartate receptors mediate a slow excitatory postsynaptic potential in the rat midbrain dopaminergic neurons.

Repetitive local application of a short train of stimuli to the rat substantia nigra and ventral tegmental area elicited a predominant depolarizing, slow, long-lasting synaptic response in the dopaminergic cells intracellularly recorded in vitro. This slow excitatory postsynaptic potential ranged between 13 and 27 mV at holding potentials of about-75 mV and lasted for 0.2-6 s. It was not greatly affected by the perfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 microM), while it was potentiated in the presence of bicuculline methiodide (30 microM) or picrotoxin (50-100 microM) and 2-hydroxysaclofen (100-300 microM). In contrast, a substantial component of the slow excitatory postsynaptic potential was reversibly depressed, in a concentration-dependent manner, by the application of the N-methyl-D-aspartate receptor antagonists D,1-2-amino-5-phosphonovalerate (10-100 microM). Furthermore, the slow excitatory postsynaptic potential was reversibly increased by the superfusion of nominally magnesium-free solution. It was graded, increasing in amplitude with increased stimulus intensity, and was blocked by tetrodotoxin (0.5 microM). We suggest that a sustained activation of synaptic terminals containing excitatory amino acids mediates a slow excitatory postsynaptic potential in the dopaminergic cells of the midbrain. N-Methyl-D-aspartate receptors participate in the generation of this slow potential, while the alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate/kainate receptors do not seem to contribute substantially to this potential. This N-methyl-D-aspartate-mediated synaptic event could be implicated in the release of dopamine as well as in the excitotoxic injury of the dopaminergic neurons.

2-Amino-5-phosphonovalerate↗

PubMedDate not supplied

Age-related decrease in the N-methyl-D-aspartateR-mediated excitatory postsynaptic potential in hippocampal region CA1.

Glutamatergic fast synaptic transmission is known to be altered with age in a region-specific manner in hippocampus of memory-impaired old rats. In the present experiment, presynaptic fiber potentials and non-N-methyl-D-aspartate (NMDAR) and NMDAR-mediated synaptic responses in CA1 were compared in three ages of behaviorally characterized male F-344 rats. In the CA1 region, old rats showed approximately equivalent reductions in non-NMDAR- and NMDAR-excitatory postsynaptic potential amplitudes for a given size of presynaptic fiber potential. There was no change in magnitude of the presynaptic response itself at any stimulus level. These results are consistent with the hypothesis that there is a reduction in the number of Schaffer collateral synapses per presynaptic axon. This pattern of results in CA1 is very different from what is known to occur at the perforant path-granule cell synapse. In fascia dentata the non-NMDAR-mediated excitatory postsynaptic potential is increased in amplitude, although the NMDAR-mediated excitatory postsynaptic potential is reduced for a given presynaptic input. These data suggest that age-related functional alterations in neurotransmitter receptor subtypes occur differentially between closely-related anatomical subregions.

Aging↗

PubMed1996

Electrical stimulation of the cholinergic laterodorsal tegmental nucleus elicits scopolamine-sensitive excitatory postsynaptic potentials in medial pontine reticular formation neurons.

A large and consistent body of data implicates mesopontine cholinergic neurons in the production of rapid eye movement sleep, and indicates that many rapid eye movement sleep events are mediated by activation of pontine reticular formation neurons. There is anatomical evidence for projections from the mesopontine cholinergic nuclei to the pontine reticular formation, but no study has shown that stimulation of this cholinergic zone produces excitatory postsynaptic potentials in pontine reticular formation neurons. In the present study, intracellular recording were made from 168 pontine reticular formation neurons, identified by antidromic activation from the bulbar reticular formation and by neurobiotin intracellular labeling, in acutely anesthetized cats. The effects of single-pulse electrical stimulation of the laterodorsal tegmental nucleus portion of the ipsilateral mesopontine cholinergic zone were evaluated in these neurons. Under urethane anesthesia this stimulation produced, in 21 of 22 recorded neurons, long-latency excitatory postsynaptic potentials (mean = 3 ms), consistent with the conduction velocity of unmyelinated cholinergic fibers (measured conduction velocity was 2 m/s). This excitatory postsynaptic potential was virtually abolished by intravenous administration of the muscarinic cholinergic receptor blocker scopolamine (n = 40 neurons), and by acute cuts separating the laterodorsal tegmental nucleus and the recorded neurons (n = 40). In contrast, a short-latency excitatory postsynaptic potential (0.7-1.5 ms) was not reduced in amplitude by scopolamine and could still be elicited following acute transverse cuts. Unlike the longer-latency excitatory postsynaptic potential, its amplitude was not reduced by barbiturate anesthesia. These data, suggesting the presence of an excitatory, cholinergic laterodorsal tegmental nucleus projection to the pontine reticular formation, provide further support to other lines of evidence implicating mesopontine cholinergic neurons in the production of rapid eye movement sleep, and are compatible with a model of rapid eye movement sleep generation in which a key element is mesopontine cholinergic input depolarizing and increasing the excitability of reticular core neurons.

Animals↗

PubMed1996

Optical studies of the biphasic modulatory effects of glycine on excitatory postsynaptic potentials in the chick brainstem and their embryogenesis.

Multiple-site optical recording of transmembrane potential activity, using a voltage-sensitive dye, was employed to monitor neural activity from the nucleus tractus solitarius of the chick embryo. Optical signals related to glutamate-mediated excitatory postsynaptic potentials were evoked by a brief square current pulse applied with a microsuction electrode to the vagus nerve, and were recorded simultaneously from many sites in the brainstem slice preparation. We have found that glycine has biphasic modulatory effects on the glutamate-mediated excitatory postsynaptic potentials: at lower concentrations, glycine enhances the glutamate-mediated excitatory postsynaptic potential-related optical signal, and at higher concentrations, it reduces the glutamate-mediated excitatory postsynaptic potential-signal. The enhancing effect was insensitive to strychnine, but the reducing effect was blocked by strychnine, suggesting that the former effect was induced by glycine which increased glutamate binding to N-methyl-D-aspartate receptors, and the latter resulted from an increase in chloride conductance through the strychnine-sensitive inhibitory glycine receptors in postsynaptic neurons. The inhibitory effect of glycine was first observed in the brainstem preparations at the seven-day-old embryonic stage, and the enhancing effect was first observed in the nine-day-old preparations. We determined regional distributions of the biphasic effects of glycine in the seven- to nine-day old embryonic preparations. The spatial distribution of the enhancing effect appeared to be concentrated on the ventral side of the nucleus tractus solitarius, and the inhibitory effect was relatively concentrated in the medial portion. Furthermore, we compared the glycine effect with the effect of Mg(2)+ on N-methyl-D-aspartate receptors, and we have found that the Mg(2)+ site is functionally organized prior to the glycine site during embryonic development.

Animals↗

PubMed1993

Behavioral parameters of the spatial memory correlate with the potentiation of the population spike, but not with the population excitatory postsynaptic potential, of the CA1 region in rat hippocampal slices.

Rats were tested for spatial performance in a water maze with further in vitro investigation of short-term and long-term potentiation (STP and LTP) in the CA1 region of the hippocampus. Recordings of the population spike in stratum pyramidale and population excitatory postsynaptic potential (EPSP) in stratum radiatum were made with extracellular electrodes after stimulation of the radiatum and oriens inputs in the region. It was found that for both inputs, STP and LTP of the population spike amplitude correlated with behavioral parameters of memory: latency of reaching the hidden platform (escape latency) and percent of time which the animal spent inside the quadrant with the platform. Potentiation of the initial slope of EPSP, in contrast, did not correlate with these parameters. These data support the hypothesis that hippocampal LTP may underlie spatial performance and show that potentiation of the output characteristic of the hippocampus (population spike), but not of the EPSP, is a physiological correlate for spatial memory.

Action Potentials↗

PubMedDate not supplied

A simple mathematical model of second-messenger mediated slow excitatory postsynaptic potentials.

We have developed a novel and simple mathematical model of a slow excitatory postsynaptic potential (EPSP) based on an abstraction of the processes of activation, inactivation, and summation of a cAMP, protein kinase A (PKA)-dependent second-messenger cascade. The model describes the activation of receptors, G-proteins, and production of cAMP as the first stage and uses first-order, non-rate-limited kinetics. The second stage corresponds to the release of active, PKA catalytic subunit and can use first- or higher-order kinetics. The third stage represents simple phosphorylation of ion channels and is limited by the number of channels available. The decay of each stage is based on first-order, mass-action kinetics. These equations and some variations were solved numerically and values of the parameters were determined by fitting to a variety of experimental data from myenteric neurons of the guinea-pig ileum. The model produced a slow EPSP with a nonlinear stimulus-response relationship that resulted from the underlying kinetics of the signaling cascade. This system of equations is suitable for incorporation into a large-scale computer simulation, and the methodology should be generalizable to other pathways.

Animals↗

PubMed2003

[Bombesin-mediated non-cholinergic late slow excitatory postsynaptic potentials in guinea pig inferior mesenteric ganglion in vitro].

The effect of bombesin (BOM) on non-cholinergic excitatory synaptic transmission of the guinea pig inferior mesenteric ganglion (IMG) was investigated by intracellular recording. Repetitive stimulation of the colon nerves (1 ms, 25 Hz, 4 s) elicited a burst of action potentials, which was followed by a long-lasting depolarization in 74.3% (52/70) of the IMG neurons. The depolarization was not blocked by nicotinic (d-tubocurarine, 100 micromol/L) and muscarinic (atropine, 1 micromol/L) antagonists, but was eliminated in a low Ca(2+)/high Mg(2+) Krebs solution, indicating that the depolarization was due to the release of non-cholinergic transmitters. Superfusing the ganglia with BOM (10 micromol/L, 1 min) induced a slow depolarization in 66.5% (109/164) neurons tested. The BOM response was not appreciably changed in low Ca(2+)/high Mg(2+) Krebs solution (n=6, P>0.05), suggesting that BOM depolarized the neurons by acting directly on the postsynaptic membrane rather than via a release of other endogenous depolarizing substances. In a total of 102 cells that exhibited late slow excitatory postsynaptic potential (ls-EPSP), superfusion of the ganglia with BOM produced a membrane depolarization in 82 neurons (80%), while the remaining 20 cells (20%) exhibited no response to BOM. In 18 neurons with ls-EPSP, 4 (22%) neurons were sensitive to both BOM and SP; 6 (33%) and 5 (28%) neurons were only sensitive to BOM and SP, respectively. The remaining 3 (17%) neurons were insensitive to both BOM and SP. Membrane resistance (Rm) had no apparent change in 47.3%, 59.5 % of the neurons tested during the ls-EPSP (n=55) and BOM depolarization (n=84), respectively, but had a marked decrease in 38.2%, 27.4%, and a marked increase in the remaining 14.5%, 13.1% of the neurons. However, when the Rm change accompanying ls-EPSP was compared with that accompanying BOM depolarization (n=20) in the same neuron, the changes in Rm were always parallel. Moreover, ls-EPSP (n=6) and BOM depolarization (n=8) were all augmented by conditioning hyperpolarization. The extrapolated values of the reversal potentials of ls-EPSP and BOM depolarization were 46.0+/-8.0 and 50.0+/-7.0 mV (n=8, P>0.05), respectively. In 14 BOM-sensitive neurons, a ls-EPSP was elicited by repetitive colon nerve stimulation. Superfusion of BOM (10 micromol/L) in these cells initially caused a large depolarization and then membrane potential gradually subsided to resting level in the continuous presence of BOM. Stimulation of the presynaptic nerves at this time failed to elicit a detecable ls-EPSP in 2 neurons and induced a much smaller one in 10 cells, while the ls-EPSP in the remaining 2 neurons was not appreciably affected. On the other hand, prolonged superfusion of BOM had no effect on the amplitude and duration of ls-EPSP in 6 BOM-insensititive neurons studied (P>0.05). The amplitude and duration of SP-induced depolarization were not altered by prolonged superfusion of BOM (n=4, P>0.05) Superfusion of tyr(4) D-phe(12) bombesin (1 micromol/L, 10 15 min), a BOM receptor antagonist, did not cause any noticeable changes in passive membrane properties nor block nicotinic f-EPSPs, but markedly suppressed (n=5) or completely abolished (n=11) BOM depolarization in all 16 neurons tested Similarly, tyr(4) D-phe(12) bombesin partially or completely antagonized the ls-EPSP in 9 out of a total of BOM sensitive neurons (n=11). The ls-EPSP elicited in the remaining two neurons was insignificantly affected by this drug. However, following 10 20 min of wash with Krebs solution the ls-EPSP was reversed. In contrast, superfusion of the ganglia with tyr(4) D-phe(12) bombesin did not change the amplitude and duration (P>0.05) of ls-EPSP in 10 BOM-insensitive cells. Similarly, the amplitude and duration of SP-induced depolarization were not appreciably affected by tyr(4) D-phe(12) bombesin (n=6, P>0.05). In conclusion, our results indicate that BOM may be another transmitter mediating the ls-EPSP in the guinea pig IMG and that there is no cross-desensitization of BOM receptors and SP receptors.

Action Potentials↗

PubMed1989

Simultaneous recording of presynaptic spikes and excitatory postsynaptic potentials from monosynaptically connected hippocampal neurons.

A technique has been devised to activate single granule cells in the hippocampus, and to record simultaneously spikes from the particular granule cell and excitatory postsynaptic potentials from a monosynaptically connected CA3 neuron. The unitary excitatory postsynaptic potentials (EPSPs) sustained for long observation periods, and increased in size with increases in stimulus frequency and in external Ca2+ concentration. This technique may be useful for quantal analysis of transmission through the synapse between mossy fibers and CA3 neurons.

Action Potentials↗

PubMed1989

Variance analysis of excitatory postsynaptic potentials in cat spinal motoneurons during posttetanic potentiation.

1. Fluctuations in the peak amplitudes of composite excitatory postsynaptic potentials (EPSPs) in cat spinal motoneurons were analyzed during posttetanic potentiation (PTP). Each of a series of identical tetanic stimulus trains delivered to a muscle nerve was followed by 45 test stimuli applied at 2-s intervals. The mean peak amplitude and mean peak variance were calculated for EPSPs evoked by all those stimuli following a tetanus with the same time interval. It was assumed that the variance arises primarily from the probabilistic all-or-none behavior of single synaptic boutons and background noise due to spontaneous synaptic activity and thermal noise in the recording system. The variance was corrected for the contribution from additive Gaussian background noise. 2. If it is assumed that individual synaptic boutons behave independently, corrected mean peak variance and mean peak amplitude are related by a parabolic function. The expected parabolic relationship was seen in 9 of 31 cases studied, and the parameters of the best parabolic fit to the data allowed estimation of some synaptic properties. From these parameters, the mean amplitude of the unit EPSP (v) was estimated to be 102.1 +/- 57.4 (SD) microV. An average of 3.7 boutons comprised each Ia-motoneuron contact system. 3. On average, only 27% of all synaptic boutons given off by the stimulated Ia fibers to one motoneuron were active and releasing transmitter during unpotentiated reflex transmission. The remaining 73% of the synapse population was intermittently silent. The population of boutons which took part in synaptic transmission could be divided into two subpopulations, one with a release probability P = 1 and a second with a mean release probability P = 0.13 +/- 0.086. 4. We conclude that synaptic boutons connecting Ia afferents to motoneurons exist in two populations, one having a high and one a low probability of transmitter release. Transmitter release is quantal, resulting in a unit EPSP of approximately 100 microV measured at the motoneuron soma.

Analysis of Variance↗

PubMed1983

On the central pattern generator for the basic breathing rhythmicity.

Recent advances in several laboratories concerning the respiration-related medullary neurons, their locations, projections, interconnections, morphological and physiological properties, and patterns of inhibitory postsynaptic potentials, excitatory postsynaptic potentials, and discharge rate, on the one hand, and the "systems behavior," on the other, have provided the basis for new hypothesis concerning the neural mechanisms underlying the central pattern generator (CPG) for breathing and its different parts. The onset of the "ramp"-like increase in inspiratory activity is due to an abrupt release of inhibition and a subsequent progressively increasing synaptic excitation of inspiratory premotor neurons. The integration of the excitatory "drive" inputs underlying the ramp inspiratory activity seems to depend on structures in the ventrorostral medulla, including nucleus paragigantocellularis. The termination of this activity by the off-switch mechanisms is actuated when a critical threshold is attained by the excitatory inputs of 1) a slowly increasing inspiration-related activity and 2) the afferent input from the pulmonary stretch receptors. The nature of the former activity is discussed. During the expiratory phase, an inhibitory activity suppresses inspiration-facilitating inputs with a slowly decaying power that controls the expiratory duration. The postinspiration activity, which brakes the rate of exhalation during the first part of the expiratory phase, depends on mechanisms separate from those responsible for the inspiratory ramp activity. The respiratory CPG seems to be organized with considerable amount of redundancy, or "degeneracity."

Biomechanical Phenomena↗

PubMed1996

Role of N-methyl-D-aspartate and metabotropic glutamate receptors in corticothalamic excitatory postsynaptic potentials in vivo.

The ventrobasal thalamus is the principal somatosensory thalamic relay nucleus, and it receives two major sources of excitatory input: firstly an input from ascending sensory afferents, and secondly a descending projection from the primary somatosensory cortex. There is considerable anatomical evidence to suggest that both of these projections utilise the excitatory amino acid L-glutamate as their neurotransmitter. Previous work from this laboratory has shown that the sensory input to the rat ventrobasal thalamus in vivo is mediated by ionotropic excitatory amino acid receptors of both the N-methyl-D-aspartate and non-N-methyl-D-aspartate type. These findings are consistent with data from other studies in various thalamic relay nuclei. In contrast, there are considerably less data available concerning the synaptic pharmacology of the corticothalamic projection although there have been both speculation and studies concerning the functional significance of this pathway. There is some evidence to suggest an involvement of N-methyl-D-aspartate receptors and metabotropic glutamate receptors. The aim of this study was to determine which excitatory amino acid receptors might mediate cortically-elicited excitatory postsynaptic potential in the ventrobasal thalamus in vivo. Intracellular recordings were made, and neurotransmitter antagonists were applied on to rat ventrobasal thalamus neurons by microiontophoresis. Cortically-elicited excitatory postsynaptic potentials were reduced by the N-methyl-D-aspartate antagonist 3-[(+/-)-2-carboxy-piperazin-4-yl]-propyl-1-phosphonate, or the Group I metabotropic antagonist (S)-4-carboxyphenylglycine. These data indicate that both N-methyl-D-aspartate receptors and Group I (possibly metabotropic glutamate receptors type I) metabotropic receptors are involved in the mediation of corticothalamic transmission. Such a transmitter mechanism would allow a modulatory system that could selectively enhance other excitatory inputs. Some of these data have been reported in abstract form.

Animals↗

PubMed1987

Excitatory postsynaptic potentials in neonatal rat sympathetic preganglionic neurons: possible mediation by NMDA receptors.

Excitatory postsynaptic potentials (EPSPs) evoked in antidromically identified sympathetic preganglionic neurons (SPNs) and membrane depolarizations induced by N-methyl-D-aspartate (NMDA) applied by pressure ejection were increased by removing Mg ions from the perfusing media and blocked by D-2-amino-5-phosphonovalerate (APV), DL-APV and ketamine. Further, the amplitude of EPSPs and NMDA-induced depolarizations were decreased and increased by membrane hyperpolarization in Krebs solution with and without Mg2+, respectively. These findings indicate that the excitatory amino acid receptor mediating the EPSPs in SPNs may be of the NMDA subtype.

Animals↗

PubMed1976

Analysis of the slow excitatory postsynaptic potential in bullfrog sympathetic ganglion cells.

The ionic mechanism of the slow excitatory postsynaptic potential (slow EPSP), i.e. the muscarinic action of acetylcholine (ACh), was studied either by stimulating preganglionic nerves or by applying ACh in curarized sympathetic ganglion cells of bullfrogs. There are three different types of cells characterized by the effects of membrane hyperpoliarization on the amplitude of slow EPSP. One group of cells showed an increase in amplitude (type 1 cell) and, in two other groups of cells, it remained unchanged (type 2 cell) or decreased (type 3 cell), when the membrane was hyperpolarized. Under the muscarinic effects of ACh, the slope membrane conductance was increased (type 1 cell), unchanged (type 2 cell) or decreased (type 3 cell) at 10-20 mV hyperpolarized levels, while it was unchanged (type 1 cell) or decreased (types 2 and 3 cells) at resting and depolarized levels. In all cells, the slow ACh potential, corresponding to the slow EPSP, was almost completely suppressed in a high K+, Ca2+-free, Na+-free solution. These results suggest that the slow EPSP is generated by increases in Na+ and Ca2+ conductance and also by a simultaneous decrease in the K+ conductance.

Acetylcholine↗

PubMed1992

Quantal parameters of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

Binomial distributions of amplitudes of excitatory postsynaptic potentials (EPSPs) mixed with Gaussian noise were simulated. The objective of Monte Carlo simulations was, firstly, to study influences of sampling size (N) and noise standard deviation (Sn) on estimates of mean quantal content (m), quantal size (v) and binomial parameters (n and p) by four methods of quantal analysis (histogram, variance, failures and combined method) based on the binomial model and, secondly, to modify these methods on the basis of comparison of estimated with simulated parameters. Reliable estimates (within +/- 10% of the simulated values) were obtained for large sample sizes (N = 500-1000) with Sn less than or equal to v by the histogram (deconvolution) method and with Sn less than or equal to 2v by the other three methods. Similar results were obtained by averages from about 10 simulations if smaller samples were used (N = 50-200). In electrophysiological experiments on slices, "minimal" EPSPs were recorded from CA1 pyramidal cells after low-intensity stimuli to stratum radiatum or stratum oriens. Amplitudes of minimal EPSPs fluctuated in a manner predicted by the quantum hypothesis. Amplitude distributions of EPSPs in the non-facilitated state were adequately described either by binomial statistics with an average p equal to about 0.4 (a range of 0.3-0.7) and an average n of about 3 (range 2-6) or by Poisson statistics with m of about 1. The quantal analysis suggests that typical values of m and v for a single activated fibre in stratum radiatum might be about 0.5-1 and 300-400 microV, respectively, with low p (0.1-0.3) and n (2-4). However, the estimates of binomial parameters should be considered as coarse approximations in view of the simulation results and a possible nonuniformity of parameter p. The comparison of results of various methods based on the binomial model, in both simulation and physiological experiments, indicates the reliability of estimates of basic quantal parameters (m and v) under realistic conditions of physiological experiments. The methods are considered to be sufficiently sensitive to make use of them for studies on mechanisms of long-term synaptic plasticity.

Animals↗

PubMed1996

Reduced corticomotoneuronal excitatory postsynaptic potentials (EPSPs) with normal Ia afferent EPSPs in amyotrophic lateral sclerosis.

We studied excitatory postsynaptic potentials (EPSPs) arising in single spinal motoneurons (composite EPSPs) induced by Ia afferent and magnetic cortical stimulation in 28 normal subjects ranging in age from 24 to 84 years and 28 patients with amyotrophic lateral sclerosis (ALS) aged 34 to 82 years. The subjects voluntarily recruited single motor units of the first dorsal interosseous muscle. Using peristimulus time histograms, we determined changes in the firing probability of the first dorsal interosseous motor units and measured the magnitude of the EPSP. An early period of increased firing probability (primary peak) occurred at approximately 30 msec after la afferent and 25 msec after cortical stimulation, reflecting underlying EPSPs arising in spinal motoneurons induced by either projection. The latency of the primary peaks for both Ia afferent and cortical stimulation was mildly prolonged in ALS, suggesting a loss of the fastest-conducting spinal motoneurons. Patients with ALS had la afferent-driven EPSPs whose amplitude and rise time were equivalent to those of normal subjects. However, the ratio of cortical to la afferent-driven composite EPSPs in ALS was significantly lower than that for normal subjects. Fourteen of 28 ALS motor units had cortically driven EPSPs that were small or large only because of a prolonged rise time. The findings suggest that in ALS, corticomotoneuronal attrition or dispersion of the descending volley occurs in the presence of normally functioning spinal motoneurons to which they project.

Adolescent↗

PubMed1994

Angiotensin II depresses glutamate depolarizations and excitatory postsynaptic potentials in locus coeruleus through angiotensin II subtype 2 receptors.

A previously reported depression of glutamate responses by angiotensin II was investigated to define the nature of this neuromodulatory effect. Studies were carried out in an vitro brain slice preparation containing the locus coeruleus, using intracellular recordings, and iontophoretic, micropressure and bath perfusion methods for application of drugs. The angiotensin action was found to be blocked by a non-peptide antagonist specific for the angiotensin type 2 receptor, and not by an antagonist selective for the type 1 receptor. Excitatory postsynaptic potentials mediated primarily by excitatory amino acids were also depressed by angiotensin II. The angiotensin II depressions of glutamate were shown to be strong and highly specific. The low effectiveness of bath-applied compared with iontophoretically or micropressure-applied angiotensin II was found to be at least partly explained by a rapid degradation by peptidases. Ammonium ions and hydrogen ions were also able to depress glutamate responses, but these effects were not specific for locus coeruleus neurons and were mediated independently of the angiotensin actions. Strong depression by angiotensin II of excitatory postsynaptic potentials as well as exogenously applied glutamate strengthens the strong possibility of a physiological role for this neuromodulatory mechanism. The identification of the type 2 angiotensin receptor subtype as the mediator of this effect indicates a novel functional role for this receptor, since previously recognized functions of angiotensin II in the brain, such as vascular and body fluid regulation, have been associated with the type 1 receptor.

Angiotensin II↗

PubMed1998

Integration of excitatory postsynaptic potentials in dendrites of motoneurons of rat spinal cord slice cultures.

We examined the attenuation and integration of spontaneous excitatory postsynaptic potentials (sEPSPs) in the dendrites of presumed motoneurons (MNs) of organotypic rat spinal cord cultures. Simultaneous whole cell recordings in current-clamp mode were made from either the soma and a dendrite or from two dendrites. Direct comparison of the two voltage recordings revealed that the membrane potentials at the two recording sites followed each other very closely except for the fast-rising phases of the EPSPs. The dendritic recording represented a low-pass filtered version of the somatic recording and vice versa. A computer-assisted method was developed to fit the sEPSPs with a generalized alpha-function for measuring their amplitudes and rise times (10-90%). The mean EPSP peak attenuation between the two recording electrodes was determined by a maximum likelihood analysis that extracted populations of similar amplitude ratios from the fitted events at each electrode. For each pair of recordings, the amplitude attenuation ratio for EPSP traveling from dendrite to soma was larger than that traveling from soma to dendrite. The linear relation between mean ln attenuation and distance between recording electrodes was used to map 1/e attenuations into units of distance (micron). For EPSPs with typical time course traveling from the somatic to the dendritic recording electrode, the mean 1/e attenuation corresponded to 714 micron for EPSPs traveling in the opposite direction, the mean 1/e attenuation corresponded to 263 micron. As predicted from cable analysis, fast EPSPs attenuated more in both the somatofugal and somatopetal direction than did slow EPSPs. For EPSPs with rise times shorter than approximately 2.0 ms, the attenuation factor increased steeply. Compartmental computer modeling of the experiments with biocytin-filled and reconstructed MNs that used passive membrane properties revealed amplitude attenuation ratios of the EPSP traveling in both the somatofugal and somatopetal direction that were comparable to those observed in real experiments. The modeling of a barrage of sEPSPs further confirmed that the somato-dendritic compartments of a MN are virtually isopotential except for the fast-rising phase of EPSPs. Large, transient differences in membrane potential are locally confined to the site of EPSP generation. Comparing the modeling results with the experiments suggests that the observed attenuation ratios are adequately explained by passive membrane properties alone.

Animals↗