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D S Faber

Publications and source records attributed to D S Faber.

At least 19 recordsLinked to original sources
PubMed1997

Nitric oxide synthase distribution in the goldfish Mauthner cell.

NADPH-diaphorase histochemical staining was used to assess the distribution of the enzyme nitric oxide synthase (NOS) in the goldfish brain, with the emphasis on the Mauthner (M-) cell, a reticulospinal neuron, and its inputs. Labeling was specific for certain cell types, including the M-cell, which stained heavily. The reaction product in this neuron was uniformly distributed along its axon, soma, and ventral and lateral dendrites. Afferents which synapse with the M-cell were also NADPH-diaphorase positive, including an identified class of inhibitory interneurons and the large myelinated club endings (LMCE) of eighth nerve fibers. The presence of NADPH-diaphorase in a lower level brainstem circuit that undergoes activity-dependent long-term potentiation of both excitatory and inhibitory synapses and is accessible for morpho-functional correlations provides the opportunity to elucidate the mechanism and role of nitric oxide at the single cell level.

Animals↗
PubMed1996

Activity-dependent short-term enhancement of intercellular coupling.

It was reported previously that repeated brief tetanization of the posterior eight nerve can produce long-term homosynaptic potentiations of the electrotonic and chemical components of the mixed EPSP evoked in the Mauthner cell lateral dendrite by a single stimulus to the nerve. We show here that the same stimulus paradigm can lead, alternatively, to short-term enhancements of both excitatory responses. These transient modifications last for approximately 3 min, with a time course similar to post-tetanic potentiation at chemical synapses. However, a different stimulus pattern that transiently increases the presynaptic calcium concentration, paired-nerve stimuli, does not have any significant effect on electrotonic transmission, whereas it facilitates the chemically mediated EPSP. On the other hand, induction of the short-lasting potentiation of coupling, which depended on the discontinuous or burst-like property of the tetanizing paradigm, required NMDA-receptor activation and was blocked by postsynaptic intradendritic injections of the calcium chelator bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid. The ineffectiveness of presynaptic calcium in potentiating electrotonic coupling likely reflects the involvement of a calcium-dependent regulatory protein in the postsynaptic cell and suggests that hemichannels on the two sides of a gap junction plaque can be modified independently. NMDA-mediated modulation of gap junctions could be widespread, because both types of channels coexist during development and in several mammalian adult central nervous system structures such as hippocampus.

Action Potentials↗
PubMed1996

Escape behavior - brainstem and spinal cord circuitry and function.

Recent work has demonstrated that the neural circuits mediating escape reactions in lower vertebrates and mammals have a common framework, with only two excitatory central synapses in the reflex arc. This relatively direct linkage from sense organs to muscles and the fact that segments of the network also transmit other motor commands help guarantee that escape always has priority over ongoing behaviors. Yet, modulation and plasticity contribute some variability to the expression of escape and, therefore, to the adequacy of its survival function.

Animals↗
PubMed1996

Diffusion, not uptake, limits glycine concentration in the synaptic cleft.

1. The question of whether active uptake limits the duration of action of the inhibitory transmitter glycine has been addressed in vivo at inhibitory synapses on the goldfish Mauthner (M) cell. The kinetics of inhibitory postsynaptic potentials and inhibitory postsynaptic currents (IPSCs) evoked antidromically and by eighth-nerve stimulation were recorded in control and in conditions expected to block glycine uptake or slow its diffusion. Theoretical considerations, based on simulated quantal currents, predicted that if diffusion was slow, rapid uptake of glycine would be required and its block would prolong the synaptic responses. 2. Temperature coefficient values for IPSC decay time constants (tau S) are in the range of 2.0 for temperatures between 15 and 23 degrees C, suggesting that diffusion is not the rate-limiting step. 3. Li+, Ch+, or N-methyl-D-glucamine were substituted for 80% of the Na+ in the extracellular fluid to analyze the effects of blocking the Na(+)-dependent glycine uptake. These procedures enhanced the maximum inhibitory shunt produced by glycine iontophoresis, leading to the suggestion that uptake may buffer the concentration of the transmitter in the cleft. In contrast, the Na+ substitutes had no effect on the tau of the recurrent collateral IPSC, which involves synchronous activation of a pool of interneurons and has a monoexponential decay (tau approximately 10-11 ms). 4. The decay phase of the disynaptic IPSCs produced by stimulating the contralateral eighth nerve has fast and slow components, with a prolonged tail lasting up to 100 ms, particularly in the case of repetitive nerve stimulation. The tail is inhibitory, as revealed by its shunt of the antidromic action potential, and it is at least partially Cl- dependent. However, it can be accelerated by superfusion with the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonopentanoic acid (APV). In the presence of these blockers, the IPSC decay remains biexponential (tau fast = 5.2 and 5.9 ms, tau slow = 94 and 130 ms for single and burst stimuli, respectively). Blocking uptake in this condition did not modify tau fast or tau slow. 5. We conclude that an active uptake mechanism does not shape glycinergic IPSCs, including the longer-lasting components that might include a contribution due to persistence of the transmitter. Rather, diffusion alone is sufficient to remove glycine at a rate faster than channel unbinding. 6. To test whether glycine might diffuse to adjacent excitatory synapses and enhance activation of N-methyl-D-aspartate receptors, CNQX and APV were applied locally, by pressure, to the M cell soma, but they had no effect on the prolonged decay of eighth-nerve-evoked responses. Thus the effects of the antagonists when added to the superfusate are exerted at the network level.

2-Amino-5-phosphonovalerate↗
PubMed1996

Properties of spontaneous inhibitory synaptic currents in cultured rat spinal cord and medullary neurons.

1. To identify the type(s) and properties of inhibitory postsynaptic receptor(s) involved in synaptic transmission in cultured rat embryonic spinal cord and medullary neurons, we have used whole cell patch-clamp techniques to record miniature inhibitory postsynaptic currents (mIPSCs) in the presence of tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. 2. The mIPSCs recorded from both spinal cord and medullary neurons had skewed amplitude distributions. 3. The glycinergic antagonist strychnine and the GABAergic antagonist bicuculline each decreased both the frequency and mean peak amplitudes of mIPSCs. We conclude that both glycine and gamma-aminobutyric acid (GABA) are neurotransmitters at inhibitory synapses in our cultured cells. 4. Most (approximately 96-97%) mIPSCs decay with single-exponential time constants, and decay time distributions were consistently best fitted by the sum of four Gaussians with decay constants as follows: D1 = 5.8 +/- 0.1 (SE) ms (n = 63), D2 = 12.2 +/- 0.2 ms (n = 61), D3 = 23.2 +/- 0.4 ms (n = 54), and D4 = 44.7 +/- 1.0 ms (n = 57). We conclude that the four classes of decay times represent kinetically different inhibitory postsynaptic receptor populations. 5. Strychnine and bicuculline usually had one of two different effects on the mIPSC decay time constant distributions; either selective decreases in the frequency of mIPSCs with decay times in certain classes (i.e., the D1 class was reduced by bicuculline, the D2 class by strychnine, and the D3 and D4 classes by both antagonists) or a nonselective depression in the frequency of mIPSCs with decay times in all four classes. The particular effect observed in a given neuron was correlated with the presence or absence of ATP and guanosine 5'-triphosphate (GTP) in the patch pipette. Namely, in 71% of the antagonist applications where the pipette contained ATP and GTP, the result was a nonselective decrease in mIPSCs in all decay time constant classes. Conversely, in 54% of the antagonist applications in their absence, the result was a selective decrease in the frequency of mIPSCs in specific decay time constant classes. 6. In some experiments, mIPSCs reappeared in antagonist solution after an essentially complete block. Recovery from block in the continued presence of antagonist was never observed in the absence of ATP and GTP (8 neurons), and, at the same time, 5 of 9 neurons patched with ATP and GTP in the pipette did show recovery (56%).

2-Amino-5-phosphonovalerate↗
PubMed1996

Inhibitory synaptic transmission in isolated patches of membrane from cultured rat spinal cord and medullary neurons.

1. To quantify the variability in the characteristics of inhibitory glycinergic and GABAergic currents at single synaptic connections between cultured rat embryonic spinal cord or medullary neurons, we have used patch-clamp techniques to record miniature inhibitory postsynaptic currents (mIPSCs) in cell-attached patches. Experiments were performed with the patch pipette containing either a low-calcium internal saline to allow comparison with subsequent whole cell recordings or external saline with tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione, a solution that is more appropriate for bathing a nerve terminal. 2. The mIPSCs recorded from the synapses restricted to the cell-attached patches were characterized by their times to peak, amplitudes, and time constants of decay. The degree of variability in these characteristics was quantified with the use of the following model-independent parameters: the coefficient of variation, skewness, and kurtosis. The distribution of time to peak values has a mean value of 5.6 +/- 0.5 (SE) ms, has the lowest coefficient of variation (0.33 +/- 0.01), is fairly symmetrical, and has a Gaussian shape with respect to peakedness. On the other hand, both the amplitude and decay time constant distributions are highly skewed and more peaked than Gaussian distributions. The mean amplitude is -6.6 +/- 0.6 pA with a coefficient of variation of 0.60 +/- 0.05, whereas the mean decay time constant is 22.8 +/- 1.0 ms with a coefficient of variation of 0.81 +/- 0.03. 3. The amplitude distributions for spontaneous inhibitory currents recorded from cell-attached patches are best fitted by the sum of multiple Gaussians. The coefficient of variation for the first Gaussian peak fitted to the amplitude distributions is 0.290 +/- 0.028. 4. Decay time distributions were consistently best fitted by the sum of four Gaussians with decay constants as follows: D1 = 5.7 +/- 0.2 ms (n = 12), D2 = 11.2 +/- 0.7 ms (n = 11), D3 = 20.6 +/- 0.8 ms (n = 12), and D4 = 43.8 +/- 2.3 ms (n = 16). These mean values are essentially identical to those reported in the preceding paper for mIPSCs recorded in the whole cell configuration. 5. In eight neurons we were able to record mIPSCs both in cell-attached patches and in subsequent whole cell configurations. The properties of mIPSCs recorded from single synapses (i.e., times to peak, amplitude, and time constants of decay) show as much variability as those of mIPSCs recorded subsequently in the whole cell mode; that is, there are no statistically significant differences in the coefficients of variation, skewness, or kurtosis for the three different distributions.

Animals↗
PubMed1996

Giant, TTX-insensitive, inhibitory postsynaptic currents in cultured rat spinal cord and medullary neurons.

1. In whole cell patch-clamp studies on cultured rat embryonic spinal cord and medullary neurons bathed in tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione, large and long-lasting spontaneous inhibitory postsynaptic currents were occasionally recorded. The amplitudes of these events were 1 order of magnitude larger than those of spontaneous miniature inhibitory postsynaptic currents. Because these large currents had reduced amplitudes in calcium-free saline and in solutions containing glycinergic or GABAergic antagonists, we conclude that they were probably produced by large and prolonged release of glycine and/or 4-amino-n-butyric acid (GABA), which subsequently bind to their postsynaptic receptors. 2. The frequency of spontaneous miniature postsynaptic currents increased dramatically during the long, slow decay phase of these large postsynaptic currents. Considering the requirement for extracellular calcium for the occurrence of these large responses, we hypothesize that this increased frequency reflected an increased intracellular calcium concentration in the presynaptic terminal. 3. Similar evidence for large inhibitory postsynaptic currents and prolonged transmitter release was observed in cell-attached patches, which also exhibited the smaller, spontaneous miniature inhibitory postsynaptic currents, suggesting that these large events are properties of single synaptic terminals. 4. A comparison of the properties of these large inhibitory postsynaptic currents recorded in whole cell mode or cell-attached patches showed no statistically significant differences. The overall mean values, then, are 13.9 +/- 1.6 (SE) ms and 4.5 +/- 0.5 s for the 10-90% rise time and duration, respectively. Furthermore, these large events had amplitudes that were 11-fold larger than the mean amplitude of the miniatures (i.e., mean amplitude ratio of 10.8 +/- 0.5). 5. Periodic large increases in the frequency of spontaneous miniature inhibitory postsynaptic currents occurred in both cell-attached patches and in the whole cell mode, and these increases were only sometimes associated with the large inhibitory postsynaptic currents. The rhythmicity in both recording configurations had similar temporal characteristics, with average interburst intervals of 5 and 12-14 s. Presumably these bursts of spontaneous miniature postsynaptic currents reflected periodic oscillations in the Ca2+ concentration in presynaptic terminals. 6. Both the probability and the frequency of occurrence of large inhibitory postsynaptic currents doubled during the 7-day period of time in culture when experiments were performed, suggesting that these large currents may play a role during development.

Animals↗
PubMed1995

"Latent" inhibitory connections become functional during activity-dependent plasticity.

Simultaneous pre- and postsynaptic recordings from identified glycinergic inhibitory interneurons and the Mauthner cell showed that 25% of the afferents produced no or extremely small postsynaptic responses. Morphological determination of the number of contacts made by these cells on the Mauthner cell revealed a connectivity similar to that of functional neurons which always produce clear inhibitory postsynaptic potentials, suggesting that most of the endings, made by weak interneurons are silent. Intraaxonal injection of 4-aminopyridine or Ca2+ greatly enhanced transmission at functional connections but did not modify those which were ineffective. However, after eighth nerve tetanic stimuli, transmission at the weak connections was unmasked or enhanced for prolonged periods and was twice as likely to be potentiated, with a 6-fold greater mean enhancement than the potent ones. This result provides additional support for long-term potentiation of inhibitory synapses. Furthermore, weakly functional junctions represent a "reserve" pool which can be critical for the expression of plasticity within a network, and, consequently, for setting the threshold of reflex activities such as the escape reaction mediated by the Mauthner cell.

4-Aminopyridine↗
PubMed1995

Regulation of synaptic strength at mixed synapses: effects of dopamine receptor blockade and protein kinase C activation.

Previous studies of the mixed excitatory synapses between eighth nerve afferents and the lateral dendrite of the goldfish Mauthner (M-) cell have shown that synaptic strength is enhanced for an hour or longer following either repeated brief tetanizations or local extracellular applications of dopamine. Both the initial electrotonic coupling potential, mediated via current flow through gap junctions, and the subsequent chemically mediated excitatory postsynaptic potentials (EPSPs) are potentiated. Different second messenger pathways are implicated in the postsynaptic induction of these potentiations, with a Ca2+ influx presumably triggering the activity dependent long-term potentiations (LTP) and dopamine acting via a cAMP dependent pathway. Experiments performed to determine whether the LTP involves a stimulus-induced release of dopamine or requires a background level of dopamine receptor activation suggest neither is the case, as tetanization in the presence of a D1 receptor antagonist, which blocks the dopamine effects, produced an LTP comparable to that in the absence of the blocker. The effects of Ca2+ are presumably not due to protein kinase C (PKC) activation, since phorbol esters had no effect on the mixed excitatory synaptic responses, although they did enhance the frequency of spontaneously occurring inhibitory PSPs.

Animals↗
PubMed1995

Retrograde synaptic communication via gap junctions coupling auditory afferents to the Mauthner cell.

Large myelinated club endings of the goldfish eighth nerve arise in the sacculus and establish mixed electrotonic and chemical synapses with the distal part of the Mauthner (M-) cell's lateral dendrite. We show here, using paired pre- and postsynaptic recordings, that depolarizing currents generated postsynaptically (specifically, the mixed synaptic potential produced by activation of part of the afferent population) can in some cases excite the presynaptic fibers and cause them to backfire. Strikingly, while in some systems junctional properties prevent the antidromic spread of depolarizing currents, physiological properties of these afferents and the gap junctions promote backfiring: the amplitude of the coupling potential recorded from an afferent fiber is voltage dependent, increasing with depolarization and being reduced during hyperpolarization. Two mechanisms, with different kinetics, underlie this voltage dependence. One, a nonlinear membrane property of the afferent fiber itself, enhances the coupling potential as the afferent membrane depolarizes. The second mechanism, which is less sensitive to voltage and is symmetric about the resting potential, most likely represents voltage dependence of the junctional membrane. Additionally, we also show retrograde diffusion of low molecular weight substances, as the fluorescent dye Lucifer yellow and the tracer Neurobiotin were found in the terminals of afferent fibers after being injected postsynaptically into the M-cell. These results suggest that the gap junctions in these primary afferents are not only involved in fast anterograde synaptic transmission but also provide the substrate for a retrograde intercellular communication. The electrical coupling may modify the input-output relation between eighth nerve afferents and the lateral dendrite by synchronizing the population of already active fibers and by promoting the recruitment of new fibers via backfiring, such that weaker inputs produce relatively larger responses.

Animals↗
PubMed1994

Automatic detection of spontaneous synaptic responses in central neurons.

A fully automatized software package for detection and measurements of randomly occurring synaptic transients embedded in background noise is described. It is based on waveform recognition protocols, allows analysis of long data segments, and provides quantitative information about event amplitudes and kinetics. Simulated postsynaptic recordings have been used to assess its performance over a wide range of conditions mimicking those seen in physiological experiments.

Animals↗
PubMed1994

Weak excitation and simultaneous inhibition induce long-term depression in hippocampal CA1 neurons.

1. Weak excitation to rat hippocampal CA1 neurons via Schaffer collaterals at a frequency of 0.1 or 0.2 Hz accompanied by repeated brief exposures to the inhibitory transmitter gamma-amino-butyric acid (GABA) causes a long-term depression (LTD, up to 90% of the control) of the stimulated pathway. This depression can be reversed by high-frequency stimulation. 2. Although inhibition is necessary for the induction of this LTD, the depression can be produced with either the GABAA or the GABAB receptor agonists. 3. This conjunctive LTD could not be blocked by the N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovaleric acid. 4. It was, however, blocked by the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionic acid and (RS)-alpha-methyl-4-carboxyphenylglycine, indicating that activation of a metabotropic glutamate receptor is necessary for the LTD. Induction also appeared to require an intracellular Ca2+ increase. 5. Because GABAergic inhibition often modulates glutamatergic transmission in the brain, we propose that this form of synaptic modification is of potential importance for neural plasticity.

Animals↗
PubMed1994

Postsynaptic modulation of synaptic efficacy at mixed synapses on the Mauthner cell.

Extracellular application of dopamine in the synaptic bed of the lateral dendrite of the goldfish Mauthner (M-) cell enhances both the electrical and chemical components of the mixed excitatory postsynaptic potential (EPSP) evoked by ipsilateral eighth nerve stimulation (Pereda et. al., 1992). We describe here results of experiments designed to determine the locus of action of dopamine and the underlying cellular mechanisms. This amine acts independently on the two modes of transmission, since (1) the percentage increases in the two were not correlated, (2) the time courses of their modifications were independent, and (3) the observed increases in synaptic responses cannot be attributed to a generalized effect on M-cell input conductance, which was increased by dopamine, a change that would rather be expected to shunt the synaptic potentials. Also, dopamine does not produce presynaptic spike broadening and does not modify paired-pulse facilitation, two indications that it acts postsynaptically. The alterations in the mixed EPSP are presumably due to activation of a postsynaptic cAMP-dependent phosphorylation pathway. Specifically, they did not occur if the cAMP-dependent protein kinase inhibitor PKI5-24 was injected intradendritically prior to dopamine application, and they could, on the other hand, be mimicked by injections of the catalytic subunit of the cAMP-dependent protein kinase, PKACAT. In contrast, neither manipulation altered the M-cell input conductance directly or affected the dopamine-induced increase in conductance, suggesting this effect of dopamine is cAMP independent.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1993

GABA responses and their partial occlusion by glycine in cultured rat medullary neurons.

Whole-cell current responses to bath application of GABA and glycine were studied in medullary neurons cultured from embryonic rats. Two current components were seen in the responses to bath application of GABA, one component which desensitized and another which did not. These two current components have different dose-response characteristics for GABA, with the nondesensitizing component being activated more effectively and reaching its peak amplitude at lower agonist concentrations than the desensitizing one. The agonist concentrations producing half of the maximum responses are 2.8 +/- 0.3 (+/- S.E.M., n = 9) and 14.7 +/- 2.7 (n = 5) microM for the nondesensitizing and desensitizing components, respectively. The two current components for GABA are differentially affected by the antagonists, picrotoxin and bicuculline. The antagonist concentrations which block 50% of the control desensitizing and nondesensitizing responses to GABA are 33 and 320 microM for picrotoxin, and 3 and 50 microM for bicuculline, respectively. Thus, the characteristics of the GABA responses are analogous to those described previously for glycine in that there are two components which are differentially sensitive to agonist concentration [Lewis et al. (1991) J. Neurophysiol, 40, 1178-1187]. We now find there is occlusion between the responses to GABA and glycine, indicating that they share a population of receptors or channels. The occlusion was incomplete (< 80%) in half of the cells, suggesting that both agonists also activate unique receptors. Furthermore, the current responses to 35 microM GABA are blocked by the glycinergic antagonist, strychnine, with half-maximal blocking concentrations equal to 2 and 30 microM for the desensitizing and nondesensitizing components, respectively. This strychnine sensitivity is less than that for the glycine receptor. At the same time, the current responses to 100 microM glycine are sensitive to the GABAergic antagonists, picrotoxin and bicuculline. The half-maximal blocking concentrations are 36 and 120 microM picrotoxin, and 120 and 500 microM bicuculline, for the desensitizing and nondesensitizing components of the glycine response, respectively. Consequently, these results suggest that these cultured cells have at least three types of inhibitory receptors: glycine receptors, GABA receptors and GABA/glycine receptors, with all three receptors sensitive to block by strychnine, bicuculline and picrotoxin. The GABA/glycine receptor may be an immature form of the inhibitory receptor. Alternatively, some GABA and glycine receptors may have common ionophores.

Animals↗
PubMed1993

Synaptic noise and multiquantal release at dendritic synapses.

1. The quantal nature of inhibitory synaptic noise recorded intracellularly from the lateral dendrite of the goldfish Mauthner cell was studied, using new detection and measurement procedures that eliminate operator intervention. In addition, we employed an analytical algorithm, not previously applied to this problem, which treats composite amplitude distributions as mixtures of gaussians of unknown separations and variances. 2. As in the soma of this neuron, the dendritic inhibitory noise is quantal, with the exception that in the dendrite multiple equally spaced classes may persist in the presence of tetrodotoxin (TTX), an observation that may be correlated with the finding that the inhibitory afferents at this level often contain more than one release site. The validity of the analysis was confirmed by superfusing with saline containing low calcium and high magnesium, which reduces composite histograms that are gaussian mixtures to a single class, equal in amplitude to that of the first component detected in the control. 3. These results suggest that spontaneous exocytotic events may be synchronized at adjacent active zones within single terminals and that lowering the probability of release by reducing calcium may then be a more effective method for isolating single miniature events than is TTX.

Animals↗
PubMed1992

Dopamine enhances both electrotonic coupling and chemical excitatory postsynaptic potentials at mixed synapses.

The transmitter dopamine reduces electrotonic coupling between retinal horizontal cells and increases their sensitivity to glutamate. Since in other systems single afferents establish mixed electrotonic and chemical excitatory synapses with their targets, dopamine might be expected there to depress one component of excitation while enhancing the other. This hypothesis was tested by applying dopamine locally in the vicinity of the lateral dendrite of the goldfish Mauthner cell (M cell) and monitoring the composite electrotonic and chemical excitatory postsynaptic potentials and currents evoked by ipsilateral eighth nerve stimulation. Dopamine produces persistent enhancements of both components of the postsynaptic response while it also increases input conductance. All these dopamine actions are prevented by superfusing the brain with saline containing the dopamine D1 receptor antagonist SCH-23390. Postsynaptic injections of the cAMP-dependent protein kinase inhibitor (Walsh inhibitor, or PKI5-24) block the dopamine-induced changes in synaptic transmission, implicating a cAMP-dependent mechanism. Furthermore, there is a dopaminergic innervation of the M cell, as demonstrated immunohistochemically with antibodies against dopamine and the rate-limiting enzyme in its synthetic pathway, tyrosine hydroxylase. Varicose immunoreactive fibers lie in the vicinity of the distal part of the lateral dendrite between the large myelinated club endings that establish the mixed synapses. As determined with electron microscopy, the dopaminergic fibers contain small vesicles, and they do not have synaptic contacts with either the afferents or the M cell, remaining instead in the synaptic bed. Taken together, these results suggest that dopamine released at a distance from these terminals increases the gain of this primary sensory input to the M cell, most likely through a phosphorylation mechanism.

Animals↗
PubMed1992

Intrinsic quantal variability due to stochastic properties of receptor-transmitter interactions.

Synaptic events at the neuromuscular junction are integer multiples of a quantum, the postsynaptic response to transmitter released from one presynaptic vesicle. At central synapses where quanta are small, it has been suggested they are invariant due to occupation of all postsynaptic receptors, a concept neglecting inherent fluctuations in channel behavior. If this did occur, the quantal release model would not apply there and could not be used to localize sites of synaptic modification. Monte Carlo simulations of quanta include transmitter diffusion and interactions with postsynaptic receptors that are treated probabilistically. These models suggest that when there are few postsynaptic channels available at a synapse, their stochastic behavior produces significant intrinsic variance in response amplitude and kinetics, and saturation does not occur. These results were confirmed by analysis of inhibitory quanta in embryonic and adult Mauthner cells involving a small and large number of channels, respectively. The findings apply to excitatory synapses as well.

Animals↗