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D S Faber

Publications and source records attributed to D S Faber.

At least 55 records · Page 3Linked to original sources
PubMed1990

Long-term potentiation of electrotonic coupling at mixed synapses.

Long-term potentiation of chemical synapses is closely related to memory and learning. Studies of this process have concentrated on chemically mediated excitatory synapses. By contrast, activity-dependent modification of gap junctions, which also widely exist in higher structures such as hippocampus and neocortex, has not been described. Here we report that at mixed synapses between sensory afferents and an identified reticulospinal neuron, the electrotonic coupling potential can be potentiated, as well as the chemically mediated excitatory postsynaptic potential, for a prolonged time period using a stimulation paradigm like that which produces long-term potentiation in hippocampus. The effect on coupling is due to an increase in gap-junctional conductance. Our data indicate that the potentiation of both synaptic components requires an increase in intracellular calcium, involves activation of NMDA (N-methyl-D-aspartate) receptors, and is specific to the tetanized pathway.

Afferent Pathways↗
PubMed1990

Glutamate stimulates release of Ca2+ from internal stores in astroglia.

We report here that, in the absence of external Ca2+, glutamate produces a transient increase in intracellular Ca2+ [( Ca2+]i) in cultured spinal cord astrocytes, by mobilizing internal Ca2+ stores. [Ca2+]i was measured with Fura-2 using the ratiometric method. Astrocytes were identified by immunostaining for glial fibrillary acidic protein. Glutamate and quisqualate consistently caused a transient increase in [Ca2+]i, with both the response amplitude and latency being graded functions of agonist concentration. Some cells produced multiple transients. N-Methyl-D-aspartate, kainate and aspartate were ineffective. We conclude that the quisqualate subtype of glutamate receptors mediates release of Ca2+ from internal stores in mammalian astrocytes.

Animals↗
PubMed1990

Developmental changes in the regulation of glycine-activated Cl- channels of cultured rat medullary neurons.

Glycine-activated currents in 1- to 11-day-old rat medullary neurons were studied using patch clamp techniques. Glycine produced neither repeatable whole-cell current responses nor single-channel activity in the cell-attached mode until cells were in culture for a week or more. However, Cl- channels were present at the early stages because glycine-activated channels were seen in excised, inside-out patches. Furthermore, for cells less than a week in culture, 10 patches which did not exhibit glycine-activated Cl- channels in the cell-attached mode did upon excision. Consequently, the activation properties of these Cl- channels undergo a developmental change in that some cellular factor(s) presumably prevents the Cl- channels from opening in the intact cell during the initial stages in culture.

Animals↗
PubMed1990

Axotomy-induced alterations in the electrophysiological characteristics of neurons.

The electrophysiological alterations provoked by axotomy have now been studied for almost half a century, in a number of different cell types. Consequently, it is now possible to detail some common mechanisms underlying these changes and to sort out certain trends in the data. The major phenomena reviewed in this section and some possible future directions are summarized below. (1) It is now possible to advance a unified hypothesis for the effects of axotomy on the conduction velocity of myelinated fibers. The key is that axon diameter, which is directly correlated with conduction velocity, is regulated, at least in part, by neurofilament protein gene expression and transport into the axon. Thus, the largest myelinated axons, with the fastest conduction velocities, have the highest neurofilament contents, and in turn, experience greater or faster declines in neurofilament content, axon caliber, and conduction speed following nerve injury. This regulation of neurofilament gene expression also appears to be target- and/or accessory cell-dependent. In fact, Hoffman and colleagues (1988) have hypothesized that neuron interactions with specific targets (via as yet unknown target-induced signals) may either specify or permit specification of the level of neurofilament gene expression in neurons. Imposed on this primary size determinant is an influence of activity, which also underlies the differential atrophy and decrement in conduction velocity exhibited by motor and sensory fibers of comparable diameters in the same lesioned nerve. Unmyelinated axons, whose structures are not dominated by neurofilament content and metabolism, react very differently to axotomy. The structural and metabolic basis of their reaction is not known. (2) Passive membrane properties, in particular neuronal input resistance, remain relatively stable in the majority of neurons after axotomy. The major exceptions, vertebrate spinal motoneurons, lamprey dorsal interneurons, and mammalian vagal motoneurons, all show an increase in input resistance after axotomy. This change in input resistance appears to be correlated with structural or geometric simplification of dendritic trees and real or apparent changes in specific membrane resistance in one case and with a reduction in cell body size in the other two; however, changes in specific membrane resistance cannot be excluded even in the latter two cases. In the spinal motoneurons, input resistance changes may be more pronounced in those neurons with the most extensive or complex dendritic geometries (i.e. F-type motoneurons). More combined electrophysiological (ideally under voltage or patch clamp conditions) and morphological investigations of single neurons need be done to resolve these questions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Transmission at a central inhibitory synapse. IV. Quantal structure of synaptic noise.

1. Continuous segments of synaptic noise were recorded, in 12 experiments, from the voltage-clamped goldfish Mauthner (M-)-cell soma during depolarizations beyond the Cl- equilibrium potential so that spontaneous inhibitory postsynaptic currents (IPSCs) were outward going, i.e., opposite in polarity to excitatory transients. Inhibitory components constituting the noise were detected with a program based on their expected waveforms, and their amplitude distributions were analyzed according to a quantal model to determine whether these responses, presumably because of asynchronous impulses in a population of presynaptic cells, were integral multiples of the same minimal unit. 2. Synaptic noise in the M-cell is predominantly inhibitory, as it is abolished by the glycine antagonist strychnine. IPSC amplitudes varied by 20-fold or more and about one-third were grouped in bursts, with one or several components often occurring during the falling phase of a preceding one. To measure individual amplitudes, a base-line correction procedure was designed to extrapolate the decay of the leading IPSC, on the assumption that it was exponential with a time constant, tau, equal to that obtained by fitting averaged waveforms of distinct IPSCs recorded in quiet periods. Currents were expressed in nanoamperes and, for comparison between experiments, as percentages of the full-sized IPSC evoked by activation of the collateral network. 3. The probability distribution functions (PDFs) of inhibitory events generated with such an analysis had from 5 to 12 clear and equally spaced peaks, larger transients not being included because of their sparsity. These PDFs were fit with a sum of Gaussians, on the assumption that all peaks were integral multiples of the smallest unit and had the same standard deviation, sigma. The fits were statistically satisfactory, according to a chi 2 test, and mean quantal size was 0.63 +/- 0.17% (SD; range, 0.42-1.0%) of the collateral IPSC. 4. In eight experiments, tetrodotoxin (TTX) was subsequently applied topically to block presynaptic impulses and isolate "miniature" responses because of single exocytotic events. It had no apparent nonspecific effects, as indicated by the constancy of M-cell input conductance (8.01 +/- 3.11 microS vs. 7.90 +/- 2.89 microS). Amplitude distributions of residual IPSCs were unimodal and Gaussian, with their mean size (0.60 +/- 0.19%) and average rise time (0.548 +/- 0.128 ms) the same as those of the first peaks of control histograms. The latter parameter was also comparable with that of unitary IPSCs studied previously. These results thus confirmed that spontaneous and evoked events are due to transmitter release from the same afferent population.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Characteristics of glycine-activated conductances in cultured medullary neurons from embryonic rat.

Characteristics of glycine-activated currents in 10- to 20-day-old neurons were studied using the gigaseal whole-cell technique. Glycine activated a Cl- conductance that was blocked by strychnine acting as a mixed inhibitor, effecting both Imax and Kd. Glycine receptors with at least two different sensitivities to strychnine were found, based on the apparent inhibition constants (Ki). These two Ki values were associated with different Hill coefficients for the glycine responses. Cs+ activated the same receptor and also activated a relatively nonselective cation conductance.

Animals↗
PubMed1989

The effects of postsynaptic levels of cyclic AMP on excitatory and inhibitory responses of an identified central neuron.

The effects of cAMP on Mauthner (M-) cell excitatory and inhibitory responses were studied in vivo. Cyclic AMP was iontophoresed into the M-cell lateral dendrite, after which we monitored the changes in cellular responsiveness to stimulation of 2 classes of identified presynaptic cells: (1) excitatory fibers from the posterior branch of the ipsilateral eighth cranial nerve and (2) inhibitory interneurons activated by the M-cell collateral and commissural networks. We found that postsynaptic injections of cAMP increased the magnitudes of the electrically and chemically mediated EPSPs from the eighth nerve and enhanced M-cell inhibitory responses as well. Furthermore, cAMP augmented paired-pulse facilitation of both types of excitatory potentials. No effects on input conductance, resting membrane potential, or presynaptic spike width were observed. All effects were mimicked by aminophylline, a cAMP-dependent phosphodiesterase inhibitor but not by 5'-AMP, the cAMP breakdown product. These results provide evidence for second-messenger modulation in vivo of electrotonic and chemical synaptic potentials at mixed synapses. In addition, they provide the first evidence for cAMP modification of a glycinergic receptor-channel complex. Preliminary results from some of these experiments have been reported previously (Wolszon and Faber, 1986).

Action Potentials↗
PubMed1988

An efferent inhibition of auditory afferents mediated by the goldfish Mauthner cell.

Intracellular recordings from goldfish auditory afferents revealed a hyperpolarization triggered by a single impulse in the Mauthner cell. The firing of either one of the two Mauthner cells alone was sufficient to evoke this potential change. The all or none hyperpolarization, which could only be recorded in some auditory fibers, presumably was an inhibitory postsynaptic potential. The inhibitory postsynaptic potential typically had a latency of 6 ms, an amplitude of 1 mV and a half-decay time of 6.8 ms; it could block or delay impulses evoked by direct current injection and could attenuate the amplitude of excitatory postsynaptic potentials evoked by sound pulses. However, this inhibitory postsynaptic potential did not reduce the amplitudes of electrotonic coupling potentials produced by antidromic impulses in the Mauthner cell. We propose that the inhibitory postsynaptic potential is generated at the dendrites of the auditory fibers, i.e. in the ear, rather than at the central terminals of the afferent, where the antidromic coupling potentials originate. The possibility that the inhibitory postsynaptic potential actually represented dis-facilitation due to an efferent inhibition of the hair cells, which tonically depolarize the saccular fibers, was ruled out because depolarization of these fibers increased the inhibitory postsynaptic potential amplitude. Possible morphological substrates for the efferent inhibition and the behavioral significance of this inhibition are discussed.

Animals↗
PubMed1988

Synergism at central synapses due to lateral diffusion of transmitter.

Recordings of inhibitory postsynaptic currents in the goldfish (Carassius auratus) Mauthner cell demonstrate nonlinear interactions when adjacent synapses are coactivated. Responses evoked by single presynaptic neurons were paired with those due to activation of a limited pool of similar inhibitory cells. In about 50% of the experiments the compound currents were substantially larger than the sum of their individual components. Potentiation was maximal when the two responses occurred nearly simultaneously, and its decay paralleled that of the conditioning current; it started with a delay of about 300 microsec, and calculations indicate that in this time transmitter molecules would diffuse laterally 0.5-1.1 micron, which equals the separation of adjacent synapses. Iontophoretically applied glycine produced a comparable enhancement of the eighth nerve evoked inhibitory current. When quantal inhibitory responses were simulated, taking into consideration glycine diffusion, transmitter-receptor interactions, and channel activation, with the latter requiring two binding steps, the results demonstrated that the facilitation when neighboring inputs are active is due to lateral diffusion of the transmitter, glycine, to fringe areas where single bound receptors are available for further interactions and channel opening.

Animals↗
PubMed1988

Unitary conductance changes at teleost Mauthner cell glycinergic synapses: a voltage-clamp and pharmacologic analysis.

1. The magnitude and kinetics of inhibitory postsynaptic currents (IPSCs) evoked in the goldfish Mauthner (M-) cell by intracellular stimulation of identified presynaptic interneurons (unitary responses) and by activation of the recurrent collateral network were determined with single-and double electrode voltage-clamp techniques. 2. The peak magnitude of the inhibitory conductance changes were 5610 +/- 4800 nS (mean +/- SD; n = 13) for the collateral response, and 144 +/- 44 nS (n = 7) for the unitary IPSCs. These synaptic conductances, which are due to the opening of Cl- channels, were independent of the degree of Cl- -loading of the M-cell. 3. The peak amplitude of the collateral inhibitory postsynaptic potential (IPSP) was a constant fraction (0.52 +/- 0.06) of the driving force, which was determined from current-voltage plots for both types of IPSCs and ranged from 10 to 37 mV. These findings confirm indirect measurements from previous current-clamp studies and validate the normalization procedure used to previously calculate synaptic conductances from IPSP amplitudes, a method that therefore may be applicable to other central neurons. 4. At the resting membrane potential, the rise time of the unitary IPSCs was 0.34 +/- 0.07 ms (n = 18), whereas their decay was exponential, with a time constant of 5.7 +/- 1.1 ms (n = 16). 5. Iontophoretic and intramuscular applications of the glycine antagonist strychnine reduced or blocked M-cell inhibitory responses, without altering the excitability of the presynaptic neurons, or the driving force. 6. Amplitude fluctuations of unitary IPSPs recorded during partial blockade by strychnine were analyzed according to a binomial model of quantal transmitter release. In one experimental series, comparison of the binomial parameters before and after applying the antagonist indicated that only quantal size, q, was reduced, whereas n, the number of available release units, and p, the probability of release, were unaffected by strychnine. In a second series, the individual presynaptic cells were injected with horseradish peroxidase (HRP), and it was found that the correlation between n and the number of stained presynaptic boutons and, therefore, of active zones, was maintained in the presence of the drug. No evidence was found for silent synapses in these conditions. 7. The quantal conductance, gq, was estimated from the binomially derived quantal size, in millivolts, and the voltage-clamp measurements of the IPSP driving force and M-cell input conductance. gq averaged 21.5 nS in control conditions and 12.3 nS in the presence of strychnine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Synaptic transmission mediated by single club endings on the goldfish Mauthner cell. I. Characteristics of electrotonic and chemical postsynaptic potentials.

Simultaneous pre- and postsynaptic intracellular recordings, combined with HRP injections, were used to study the properties of junctional transmission between club endings of saccular nerve afferents and the Mauthner (M-) cell in goldfish. All endings were electrotonically coupled to the M-cell, but impulses in less than 20% of the afferents produced chemically mediated excitatory postsynaptic potentials as well. There were no differences between the coupling potentials of those endings that mediated chemical transmission and those that did not, and presynaptic injections of HRP confirmed that in both cases the studied fibers terminated on the M-cell as single club endings. Since electron microscopic studies (Nakajima, 1974; Kohno and Noguchi, 1986; Tuttle et al., 1986) have consistently revealed structural correlates of chemical synapses in all the endings, we propose that the chemical synapses in the majority of the club endings are functionally silent. The electrotonic coupling at these junctions was characterized on the basis of coupling coefficients and DC transfer resistances. Coupling coefficients for anti- and orthodromic action potentials averaged 0.076 and 0.011, respectively. The transfer resistances measured with injections of constant-current pulses were the same in both directions (approximately 18.6 k omega), indicating the junctions do not rectify. Two separate calculations of the gap junctional resistance indicated that it is in the range of 6.7-35.8 M omega, with a mean value of 15.5 M omega. This calculated junctional resistance corresponds to 670 open gap junction channels, assuming a single-channel conductance of 100 pS. As that estimate is about 2 orders of magnitude smaller than the number of the presumed morphological correlates of the channels, i.e., intramembranous particles observed with the technique of freeze-fracture (Kohno and Noguchi, 1986; Tuttle et al., 1986), we conclude that only a small fraction of the morphologically observed channels are open at any time. The characteristics of the chemically mediated EPSPs were as follows: amplitude, 0.139 +/- 0.075 mV (mean +/- SD; n = 16); latency from onset of the coupling potential, 636 +/- 26 mu sec (n = 24); 10-90% rise time, 244 +/- 33 mu sec (n = 14); and decay time constant, 1.32 +/- 0.51 msec (n = 6). The decay phase was fit by a single exponential, and its time constant presumably is the same as that of the underlying conductance change since the M-cell's membrane time constant is significantly faster, 0.3-0.4 msec.

Algorithms↗
PubMed1988

Synaptic transmission mediated by single club endings on the goldfish Mauthner cell. II. Plasticity of excitatory postsynaptic potentials.

Simultaneous pre- and postsynaptic intracellular recordings were used to analyze the properties of chemically mediated synaptic transmission between single club endings of eighth nerve afferents and the goldfish Mauthner (M-) cell lateral dendrite. The EPSPs exhibited pronounced facilitation when the presynaptic fiber fired high-frequency bursts of 2 or 3 impulses at intervals of 2-4 msec. The amplitudes of the EPSPs evoked by the second and third presynaptic impulses of a burst were, on average, 99 and 108% larger than that evoked by the first impulse. A cross-correlation analysis showed that the amplitudes of the control and facilitated EPSPs fluctuated independently, indicating that the facilitation was mediated by a presynaptic mechanism. This conclusion was supported by a comparison of the coefficient of variation for the control and facilitated EPSPs, on the basis of a binomial release model. In addition, the value of binomial n, the number of presynaptic release units, was not changed during facilitation. The origin of EPSP fluctuations was analyzed by examining the correlation between the amplitudes of EPSPs and those of the electrotonic coupling potentials associated with them. The absence of correlation between the 2 variables suggested that the fluctuations of EPSPs were not due to a variable presynaptic impulse invasion. The EPSP fluctuations were further analyzed by assuming that the facilitation was associated with an increase in the probability (p) of transmitter release and that the release process followed simple binomial statistics. The binomial variables thus calculated were n = 6-11, p = 0.29-0.44, and q = 31-61 microV, values comparable to the estimates for other CNS synapses. More importantly, these parameters provided satisfactory fits to the amplitude histograms of the control and facilitated EPSPs. The number of release units, n, was smaller than, but in a range similar to, the number of active zones identified in the freeze-fracture study of the club endings (Kohno and Noguchi, 1986). This correlation is consistent with the notion that active zones are the structural correlates of quantal release units. In the preceding paper, it was shown that impulses in a majority of club endings electrotonically coupled to the M-cell do not produce a detectable chemically mediated EPSP, although the contacts have the morphological correlates of chemical synapses. In an attempt to activate these "silent" connections, 2 approaches were used. First, the burst-firing paradigm, which could effectively facilitate EPSPs already present, failed to reveal any EPSPs at the silent junctions.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed1988

Identification of motoneurons and interneurons in the spinal network for escapes initiated by the mauthner cell in goldfish.

We used intracellular recording and staining techniques to study the spinal circuitry of the escape behavior (C-start) initiated by the Mauthner axon (M-axon) in goldfish. Simultaneous intracellular recordings from one or both M-axons and a spinal neuron, followed by HRP labeling of the spinal cell, show that each M-axon makes monosynaptic, chemical excitatory synapses onto 2 populations of ipsilateral spinal neurons. The first consists of the large primary motoneurons that, based on earlier work (Fetcho, 1986), innervate exclusively the faster, white muscle fiber types in the myomeres. The second group of cells is formed by previously undescribed descending interneurons with ipsilateral axonal branches that have contacts with primary and secondary motoneurons spread over 2 or more body segments. Indirect evidence suggests that these descending interneurons are excitatory, and they may explain the polysynaptic activation of motoneurons observed in earlier studies of the spinal circuitry (Diamond, 1971). Both classes of neurons excited by the ipsilateral M-axon are disynaptically inhibited by the contralateral one. The morphology and physiology indicate that this inhibition is mediated by interneurons that are electrotonically coupled to one M-axon and have processes that cross the cord to inhibit contralateral neurons in the region where these postsynaptic cells receive excitatory input from the other M-axon. We have identified interneurons with the physiological and morphological features of these predicted crossed inhibitory interneurons. These cells are electrotonically coupled to the ipsilateral M-axon and receive a chloride-dependent disynaptic inhibitory input from the contralateral M-axon. Their very simple somata give rise to a process that crosses the spinal cord between the 2 M-axons. Once on the opposite side of the cord, the crossing process sends myelinated branches that run rostrally and caudally, roughly parallel to the contralateral M-axon. Processes that arise from these longitudinal branches terminate in a striking association with collaterals of the M-axon; nearly every M-axon collateral along the longitudinal course of an interneuron is met by a branch or branches of the interneuron whose terminals are apposed to neurons postsynaptic to the collateral.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Spinal inputs to the ventral dendrite of the teleost Mauthner cell.

Ascending excitatory inputs from the periphery to the ventral dendrite of the goldfish Mauthner (M)-cell are characterized in this report. Direct stimulation of the spinal cord, at strengths suprathreshold for antidromic activation of the M-axon, evoked a graded excitatory postsynaptic potential (EPSP) in the distal ventral dendrite of the cell. This localization was demonstrated by multiple intracellular recordings from the soma and dendritic loci. The EPSP had a relatively long latency (mean = 3.6 ms) and contained multiple components. Furthermore, the EPSP amplitudes were extremely sensitive to frequency, being reduced by more than 50% at frequencies of 1-2 Hz and maximal with interstimulus intervals of 30-60 s. The spinal input is, therefore, likely to be mediated by a polysynaptic pathway. Direct stimulation of the skin surface evoked similar EPSPs, in terms of latency, wave form, graded nature, frequency dependence and spatial distribution on the M-cell ventral dendrite. Thus, the spinal cord and skin inputs probably relay somatosensory information from the trunk to the M-cell ventral dendrite. This notion was further confirmed by an interaction study of the EPSPs evoked from the two sites. We also report that the ventral dendrite does not support active spike electrogenesis, as indicated by the spatial profile of the M-cell antidromic impulse amplitude.

Afferent Pathways↗
PubMed1987

Localization of optic tectal input to the ventral dendrite of the goldfish Mauthner cell.

Although visually evoked Mauthner cell (M-cell) startle responses occur in the goldfish, the afferent projections underlying these reactions have not been previously studied. We have recorded from the M-cell while stimulating the left optic nerve and/or right optic tectum and have traced projections of the optic nerve and restricted areas of the optic tectum using HRP histochemistry and autoradiography. Tectal stimulation elicits similar postsynaptic potentials (PSPs) in both M-cells. The responses recorded in the right (ipsilateral) cell were localized to its ventral dendrite. The existence of uncrossed tectal projections to the ventral dendrite was confirmed morphologically following application of horseradish peroxidase (HRP) to the optic tectum. The PSPs contained both inhibitory and excitatory components, but with adequate stimulus strength, excitation of either M-cell dominated. Thus, this pathway is probably sufficient to trigger visually evoked startle responses mediated by the M-cell. Stimulation of the left optic nerve also evoked PSPs capable of bringing both M-cells to threshold. The blockage of this response by conditioning stimulation of the right tectum suggests that the visual information is relayed to the M-cells through this structure. In support of these findings, no label was found near any portion of the M-cell after either intraocular injection of tritiated proline or application of HRP to the cut end of the optic nerve. In summary, visual input to the M-cell is mediated via projections from the tectum, is segregated onto the ventral dendrite, and is capable of bringing this neuron to threshold. This pathway presumably accounts for the demonstrated behavioral efficacy of visual stimuli in evoking a startle response.

Animals↗