Biomedical subjects

B Walmsley

Publications and source records attributed to B Walmsley.

At least 19 recordsLinked to original sources

PubMed2000

Phosphorylation regulates spontaneous and evoked transmitter release at a giant terminal in the rat auditory brainstem.

1. The role of phosphorylation in synaptic transmission was investigated at a large glutamatergic terminal, the endbulb of Held, on bushy cells in the rat anteroventral cochlear nucleus (AVCN). 2. Whole-cell recordings of excitatory postsynaptic currents (EPSCs) were used to examine the effects of kinase inhibitors and activators on low-frequency (baseline) evoked release, spontaneous release, paired-pulse facilitation (PPF) or depression (PPD), repetitive stimuli and recovery from depression. 3. Application of the kinase inhibitor H7 (100 microM) reduced low-frequency evoked EPSC amplitude (by 15 %) and simultaneously increased PPF (or reduced PPD), with no significant change in other aspects of transmission. H7 did not affect the amplitude or frequency of spontaneous miniature EPSCs. 4. Phorbol esters increased EPSC amplitude (by 50 %) with a concomitant decrease in PPF (or increase in PPD), and reduced the final EPSC amplitude during repetitive stimuli. The effect of phorbol esters was due exclusively to protein kinase C (PKC) activation, as the specific PKC inhibitor bis-indolylmaleimide (Bis) completely blocked the potentiating effect of phorbol esters on EPSC amplitude. 5. Significantly, phorbol esters did not increase the evoked EPSC amplitude at connections in which release was maximized using high extracellular calcium concentrations (4-6 mM). 6. Phorbol esters increased the frequency of spontaneous miniature EPSCs in physiological calcium (by 275 %), and in high extracellular calcium (by 210 %) when phorbol esters did not increase the evoked EPSC amplitude. 7. Our results are most consistent with the actions of H7 to decrease low-frequency release probability and phorbol esters to increase low-frequency release probability at the endbulb-bushy cell synaptic connection in the AVCN. The effects of H7 and phorbol esters on paired-pulse responses and tetanic depression appear to be largely consequential to these changes in low-frequency release probability.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

GABA mediates presynaptic inhibition at glycinergic synapses in a rat auditory brainstem nucleus.

Many inhibitory nerve terminals in the mammalian anteroventral cochlear nucleus (AVCN) contain both glycine and GABA, but the reason for the co-localization of these two inhibitory neurotransmitters in the AVCN is unknown. We have investigated the roles of glycine and GABA at synapses on bushy cells in the rat AVCN, using receptor immunohistochemistry and electrophysiology. Our immunohistochemical results show prominent punctate labelling of postsynaptic clusters of glycine receptors and of the receptor clustering protein gephyrin over the surface of bushy cells. In contrast, weak diffuse membrane immunolabelling of GABAA receptors was observed. Whole-cell recordings from bushy cells in AVCN slices demonstrated that evoked inhibitory postsynaptic currents (IPSCs) were predominantly (81 %) glycinergic, based on the decrease in amplitude of the IPSCs in bicuculline (10 microM). This observation was supported by the effect of strychnine (1 microM), which was to decrease the evoked IPSC (to 10 % of control IPSC amplitude) and to produce a greater than 90 % block of spontaneous miniature IPSCs. These results suggest a minor role for postsynaptic GABAA receptors in bushy cells, despite a high proportion of GABA-containing terminals on these cells. Therefore, a role for metabotropic GABAB receptors was investigated. Activation of GABAB receptors with baclofen revealed a significant attenuation of evoked glycinergic IPSCs. The effect of baclofen was presynaptic, as indicated by a lack of change in the mean amplitude of spontaneous IPSCs. Significantly, the decrease in the amplitude of evoked glycinergic IPSCs observed following repetitive nerve stimulation was reduced in the presence of the GABAB antagonist, CGP 35348. This indicates that synaptically released GABA can activate presynaptic GABAB receptors to reduce transmitter release at glycinergic synapses. Our results suggest specific pre- versus postsynaptic physiological roles for GABA and glycine in the AVCN.

Animals↗

PubMed2000

Release probability modulates short-term plasticity at a rat giant terminal.

1. Modulation of release probability is a major factor underlying short-term synaptic plasticity in the central nervous system. We have investigated the relationship between release probability ((Pr) and paired-pulse modulation at a large auditory calyceal synapse containing many transmitter release sites. Whole-cell patch electrode recordings were made of excitatory postsynaptic currents (EPSCs), evoked by stimulation of auditory nerve fibres giving rise to the endbulbs of Held. 2. Quantitative estimates of Pr and quantal amplitude were obtained using the recently developed variance-mean analysis technique. Release probability conditions were modulated by bath application of cadmium, elevated calcium and protein kinase C activation by phorbol esters. 3. Our results show that, under physiological conditions, most sites released neurotransmitter following a single presynaptic nerve impulse, with a mean Pr of 0.6. The mean quantal amplitude was 44 pA, which was consistent with the mean amplitude of miniature EPSCs (47 pA). 4. Under high release probability conditions with elevated calcium or phorbol esters, Pr at all sites approached 1.0. At these high Pr values, variance-mean analysis indicated a significant postsynaptic contribution to paired-pulse depression. The miniature EPSC amplitudes were decreased following stimulation in elevated calcium, confirming a postsynaptic component of paired-pulse depression at this glutamatergic connection. 5. A notable feature was the large variability between neurons in the relationship between paired-pulse ratio and Pr. Based on current models of vesicle release and ultrastructural evidence, we suggest that this variability may be partly due to morphological differences between endbulb specializations, particularly in the ratio of fusion-ready to reserve populations of vesicles at endbulb release sites.

Animals↗

PubMed1999

Quantal size is correlated with receptor cluster area at glycinergic synapses in the rat brainstem.

1. Whole-cell patch electrode recordings of glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were obtained in neurons of the rat anteroventral cochlear nucleus (AVCN). Mean mIPSC peak amplitude was found to vary considerably between AVCN neurons (range, -19.1 to -317.9 pA; mean +/- s.d., -159.1 +/- 100.7 pA; 14 cells). 2. Immunolabelling of glycinergic receptor clusters in AVCN neurons was performed using antibodies against the glycine receptor clustering protein gephyrin. Measurements of the area of gephyrin immunoreactive clusters were obtained using confocal fluorescence microscopy. These measurements showed a large variability in cluster area, not only in the same cell (mean coefficient of variation, c.v., 0.66 +/- 0.18; 16 cells), but also in mean cluster area between cells (range, 0.21-0.84 microm2; 16 cells). 3. A possible relationship between mIPSC amplitude and receptor cluster area was investigated in a further series of experiments, in which mIPSCs recordings and immunolabelling of glycine receptor clusters were obtained for the same cells. In these experiments, AVCN neurons were identified using intracellular labelling with neurobiotin. Successful results using a combination of whole-cell recordings, neurobiotin identification and immunolabelling were obtained for a total of 10 AVCN neurons. Analysis of the results revealed a positive, statistically significant correlation between mean receptor cluster size and mean mIPSC amplitude (P < 0.05, 10 cells, Spearman's correlation test). 4. These results provide direct experimental evidence supporting a hypothesis of central glycinergic transmission in which synaptic strength may be regulated by changes in the size of the postsynaptic receptor region.

Animals↗

PubMed1999

A novel presynaptic inhibitory mechanism underlies paired pulse depression at a fast central synapse.

Several distinct mechanisms may cause synaptic depression, a common form of short-term synaptic plasticity. These include postsynaptic receptor desensitization, presynaptic depletion of releasable vesicles, or other presynaptic mechanisms depressing vesicle release. At the endbulb of Held, a fast central calyceal synapse in the auditory pathway, cyclothiazide (CTZ) abolished marked paired pulse depression (PPD) by acting presynaptically to enhance transmitter release, rather than by blocking postsynaptic receptor desensitization. PPD and its response to CTZ were not altered by prior depletion of the releasable vesicle pool but were blocked by lowering external calcium concentration, while raising external calcium enhanced PPD. We conclude that a major component of PPD at the endbulb is due to a novel, transient depression of release, which is dependent on the level of presynaptic calcium entry and is CTZ sensitive.

Animals↗

PubMed1999

Glycinergic miniature synaptic currents and receptor cluster sizes differ between spinal cord interneurons.

The structural features of a synaptic connection between central neurons play an important role in determining the strength of the connection. In the present study, we have examined the relationship between the structural and functional properties of glycinergic synapses in the rat spinal cord. We have analyzed the structure of glycinergic receptor clusters on rat ventral horn interneurons using antibodies against the glycine receptor clustering protein, gephyrin. We have examined the properties of quantal glycinergic currents generated at these synapses using whole cell patch-clamp recordings of miniature postsynaptic inhibitory currents (mIPSCs) in rat spinal cord slices in vitro. Our immunolabeling results demonstrate that there is a considerable variability in the size of glycine receptor clusters within individual neurons. Furthermore there are large differences in the mean cluster size between neurons. These observations are paralleled closely by recordings of glycinergic mIPSCs. The mIPSC amplitude varies significantly within and between neurons. Results obtained using combined immunolabeling and electrophysiological recording on the same neurons show that cells with small glycine receptor clusters concurrently exhibit small mIPSCs. Our results suggest that the differences in the size of glycinergic receptor clusters may constitute an important factor contributing to the observed differences in mIPSC amplitude among spinal cord interneurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1998

Developmental changes in EPSC quantal size and quantal content at a central glutamatergic synapse in rat.

1. Developmental changes in amplitude and time course of single-fibre-evoked and spontaneous EPSCs mediated by AMPA and NMDA receptors at the endbulb-bushy cell synapse of rats from 4 to 22 days of age were recorded using whole-cell patch-clamp methods in in vitro slices of cochlear nucleus. 2. The mean conductance of the AMPA component of evoked EPSCs increased by 66 %, while that of the NMDA component decreased by 61 %, for 12- to 18-day-old rats cf. 4- to 11-day-old rats. 3. The mean AMPA spontaneous EPSC conductance increased by 54 %, while mean NMDA spontaneous EPSC conductance decreased by 83 %, for 12- to 22-day-old rats cf. 4- to 11-day-old rats. The mean number of quanta contributing to peak evoked AMPA conductance also increased by 78 % in the older age group, after correction for the asynchrony of evoked quantal release. 4. The decay time constant of spontaneous AMPA EPSCs showed a small decrease in older animals, while the decay time constant of spontaneous NMDA EPSCs was markedly decreased in older animals. The decay time constants of evoked NMDA EPSCs showed a quantitatively similar decrease to that of spontaneous NMDA EPSCs. This suggests that AMPA receptor subunit composition is unlikely to undergo developmental change, while NMDA receptor subunit composition may be substantially altered during synaptic maturation. 5. These data are consistent with a developmentally increased efficacy of AMPA receptor-mediated synaptic transmission at the endbulb-bushy cell synapse, due to an increase in underlying AMPA-mediated quantal size and content during the same period as a transient co-localization of NMDA receptors.

Animals↗

PubMed1998

Diversity of structure and function at mammalian central synapses.

Our appreciation of the relationship between synaptic structure and function, and in particular our understanding of quantal synaptic transmission, is derived from classical studies on the neuromuscular junction. However, physiological studies of quantal transmission at mammalian CNS synapses have produced a variety of results, and thus no consensus of opinion has emerged. This variability could be due, in part, to experimental and analytical limitations or to differences in the structural and functional features of central synapses, or both. Some of the experimental limitations have recently been overcome by the use of novel preparations that permit direct measurement of quantal synaptic events in the CNS. Although these studies reveal similarities between the synaptic mechanisms of the neuromuscular junction and CNS synapses, important differences and specializations are also evident. The purpose of this review is to highlight the structural and functional diversity of synapses in the mammalian CNS, and to discuss the potential relevance of structural features to synaptic function.

Animals↗

PubMed1998

Signalling at the synapse: regulation of the post-synaptic response to quantal transmitter release.

Communication between neurones in the central nervous system occurs at specialized synaptic contacts. The strength of a synaptic signal is precisely regulated, and modification of synaptic strength is important in complex brain functions such as learning, and in the formation of appropriate neural maps during development. The fundamental building block of synaptic signalling is the post-synaptic current generated in response to the pre-synaptic release of a quantum of neurotransmitter. The present short review examines the factors that determine the quantal post-synaptic current, and provides direct evidence from a recent study in the author's laboratory that regulation of quantal size is important during development of excitatory transmission in the auditory system.

Animals↗

PubMed1996

Amplitude and time course of evoked and spontaneous synaptic currents in rat submandibular ganglion cells.

1. Excitatory postsynaptic currents (EPSCs) were recorded in rat submandibular ganglion cells in vitro using the two-electrode voltage clamp technique. 2. The peak amplitude of EPSCs evoked by nerve impulses in single presynaptic fibres varied between 1.2 and 9.8 nA in different cells (mean = 4.6 +/- 2.6 nA; n = 23; -80 mV membrane potential; 22-25 degrees C). 3. Experiments were performed to re-investigate a previous hypothesis that different mechanisms underlie the generation of evoked versus spontaneous quantal EPSCs in submandibular cells. This hypothesis was based on the observation of different time courses of evoked and spontaneous EPSCs. 4. In agreement with previous studies, the time course of the decay phase of evoked EPSCs was described by the sum of two exponentials, with time constants tau 1 and tau 2 of 6.9 +/- 0.7 and 34.4 +/- 7.7 ms, respectively (n = 23; -80 mV membrane potential). 5. The double-exponential decay of evoked EPSCs persisted when transmitter release was reduced by bath addition of 100 microM cadmium chloride to the level of failures, one or several quanta. 6. Spontaneous EPSCs exhibited mean amplitudes of 81 +/- 24 pA (n = 5 cells; -80 mV membrane potential), and displayed an extremely wide range of peak amplitudes in the same cell (mean coefficient of variation (c.v.) = 0.37 +/- 0.09; n = 5 cells). In contrast to a previous report (see below), the decay phase of spontaneous EPSCs was found to exhibit a double-exponential time course with time constants similar to those of the evoked EPSC recorded in the same cell. 7. These results indicate that evoked and spontaneously released quanta of transmitter most probably act on the same population of postsynaptic receptors in submandibular ganglion cells. There is a large variability in the peak amplitudes of quantal EPSCs recorded in the same cell. This large variability is not due to electrotonic effects, since these cells lack dendrites.

Animals↗

PubMed1996

Amplitude and time course of spontaneous and evoked excitatory postsynaptic currents in bushy cells of the anteroventral cochlear nucleus.

1. Spontaneous and evoked excitatory postsynaptic currents (EPSCs) were recorded in slices of the rat anteroventral cochlear nucleus (AVCN) at the endbulb-bushy cell synaptic connection. 2. The amplitudes of alpha-amino-3-hydroxy-5-methy-4-isoxa-zolepropionic acid (AMPA)-receptor-mediated spontaneous EPSCs were large (54 +/- 6 pA, mean +/- SD; membrane potential = -70 mV, 22-25 degrees C) and, in the same cell, exhibited a very wide range of peak amplitudes (CM = 0.42 +/- 0.01, n - 15 cells). There was no significant correlation between rise times or decay time constants and the peak amplitudes of spontaneous EPSCs recorded in the same cell, demonstrating that electrotonic attenuation is not responsible for the large amplitude variability of spontaneous EPSCs. 3. Cyclothiazide, a potent blocker of AMPA-receptor desensitization, did not affect the amplitude of spontaneous EPSCs in AVCN bushy cells, suggesting that background desensitization of AMPA receptors is not significant in these cells. However, the decay time constant of spontaneous EPSCs was prolonged significantly (2.6-fold increase). In addition, cyclothiazide produced a marked increase (approximately 40%, n = 6 cells) in the frequency of spontaneous EPSCs, indicating a likely presynaptic site of action of this drug. 4. Cyclothiazide produced a small increase (approximately 10%, n = 7 cells) in the peak amplitude of the evoked endbulb EPSC, but this effect could be explained by the action of cyclothiazide to increase the decay time constant of the underlying quantal EPSCs in conjunction with the asynchrony of quantal transmitter release at the endbulb synapse. 5. These results indicate that neither electrotonic attenuation nor receptor desensitization are responsible for the wide range of peak amplitudes of spontaneous EPSCs in bushy cells. The large quantal variability therefore is likely to be due entirely to intrinsic fluctuations at each release site and site-to-site variability in the numbers of available receptors.

Animals↗

PubMed1995

Interpretation of 'quantal' peaks in distributions of evoked synaptic transmission at central synapses.

At some synaptic connections in the central nervous system, amplitude distributions of evoked synaptic currents exhibit surprisingly sharp and regularly spaced peaks. At these connections, detailed analysis of the peaks has led to the proposal that the 'quantal' synaptic current displays very little variability, not only at a release site, but also between release sites. In this study the latter hypothesis has been tested using simulations of evoked transmission. In contrast with previous conclusions, these simulations demonstrate that the experimental observation of regularly spaced peaks in amplitude distributions of synaptic currents is compatible with large underlying differences in the synaptic current amplitudes between release sites. The simulations also reveal that quantal analysis based entirely on the observation and analysis of regularly spaced peaks in evoked synaptic current amplitude distributions, cannot be used with confidence to estimate presynaptic release probabilities, 'quantal' current amplitudes at each release site, or the total number of available release sites. This problem may be a confounding factor in determining whether pre- or postsynaptic changes underlie alterations in synaptic efficacy, such as occurs during long term potentiation.

Animals↗

PubMed1995

Counting quanta: direct measurements of transmitter release at a central synapse.

Contradictory hypotheses regarding the nature of synaptic transmission in the CNS have arisen from indirect methods of quantal analysis. In this study, we directly count the quanta released following nerve stimulation to examine synaptic transmission at a fast glutamatergic synapse in the mammalian auditory brainstem. Our results demonstrate the relationship between spontaneous and nerve-evoked synaptic events, indicate that asynchronous transmitter release governs the time course of evoked transmission, and show that the stochastic quantal release process, as originally proposed at the neuromuscular junction, is highly conserved at this central synapse.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Receptors underlying excitatory synaptic transmission in slices of the rat anteroventral cochlear nucleus.

1. The anteroventral cochlear nucleus (AVCN) contains two principal cell types that receive input from the auditory nerve. Stellate cells receive conventional synapses on their dendrites, and bushy cells of the AVCN receive axosomatic input via large, calyceal terminals (the end bulbs of Held). We have used whole cell patch-clamp recording techniques to study excitatory postsynaptic currents (EPSCs) in these two principal cells of the rat AVCN. 2. EPSCs evoked in stellate cells by stimulation of the auditory nerve were graded with stimulus strength, indicating a high degree of convergence of input to these cells. At depolarized membrane potentials, EPSCs evoked in stellate neurons had a dual-component time course. The slow component was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV), and the fast component was abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. EPSCs evoked in bushy cells by auditory nerve stimulation were large (50 nS average conductance) and all-or-none at the threshold stimulus level. At -70 mV, the time course of the EPSC was very brief (average time constant of decay 700 microseconds at room temperature). Membrane depolarization revealed a slow component to the EPSC. The fast and slow components were mediated by non-NMDA and NMDA receptors, respectively. The switch-off of end bulb NMDA EPSCs by voltage jumps to the EPSC reversal potential was very rapid, suggesting that the NMDA component arises from sites on or close to the soma. 4. Miniature EPSCs, recorded in the presence of tetrodotoxin (TTX) at depolarized potentials, also had a dual-component time course. The fast and slow components of the miniature EPSCs were blocked by CNQX and APV, respectively. This result indicates that NMDA and non-NMDA receptors can be co-localized at the same, presumably end bulb, release sites. 5. The relative contribution of the slow, NMDA component to the end bulb EPSC declined significantly with age (postnatal days 11-22). 6. These results indicate that both NMDA and non-NMDA receptors underlie excitatory synaptic transmission in the AVCN of young rats. The end bulb synapse onto bushy cells generates a non-NMDA receptor-mediated EPSC with very fast kinetics. NMDA receptors can also mediate synaptic transmission at the end bulb synapse, but their contribution becomes less as the auditory system matures. This finding suggests that NMDA receptors may play an important role in the development of this synapse.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Serial E-M and simulation study of presynaptic inhibition along a group Ia collateral in the spinal cord.

1. A muscle spindle primary afferent (group Ia) was physiologically identified and labeled intracellularly with the use of horseradish peroxidase (HRP) in the cat lumbar spinal cord. Serial-section electron microscopy (EM) was used to examine and reconstruct an entire axon collateral and its branches within Clarke's column. In the present study the existence and location of presynaptic contacts on Ia afferent boutons along these collateral branches were determined from examination of the serial-section electron-micrographs. 2. Of 36 Ia boutons examined in serial sections along the branches of the same collateral, 3 presynaptic contacts were found. Two of these contacts were made with Ia boutons in a complex nodal region consisting of two unmyelinated side branches exhibiting a total of six Ia boutons. The other presynaptic contact was made with a Ia bouton in a nodal region consisting of two Ia boutons connected by a thin unmyelinated bridge. 3. Computer simulations, based directly on the serial-section-reconstructions, were used to investigate the possible effects of these presynaptic contacts on membrane potential and on a propagating action potential along the Ia collateral. The effect of a presynaptic contact was modeled by a sustained gamma-aminobutyric acid-A (GABAA)-activated chloride conductance. 4. The simulation results indicated that the effect of a presynaptic contact on membrane potential and action-potential amplitude is likely to extend beyond the contacted bouton to other boutons occurring along the short unmyelinated branches arising from the same node.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1994

An in vivo pharmacological study of single group Ia fibre contacts with motoneurones in the cat spinal cord.

1. Direct experimental evidence was obtained on the spatial distribution of active synaptic contacts from single Ia muscle afferents on the dendrites of lumbosacral motoneurones in anaesthetized cats. 2. An extracellular micropipette was used to pressure eject the AMPA/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX) in close proximity to the intracellular recording site, in order to create an extracellular concentration gradient of the antagonist. The effect of antagonist ejection on the time course and amplitude of excitatory postsynaptic potentials (EPSPs) evoked in motoneurones by impulses in single group Ia fibres was examined. 3. Pressure ejection of NBQX resulted in a complete block of the monosynaptic group Ia EPSP in two cells, and a significant reduction to 23-57% of control EPSP peak amplitudes in a further six cells (mean, 27%; n = 8). These effects were not associated with changes in membrane potential or membrane time constant. 4. The reduction in amplitude of these single group Ia fibre EPSPs following ejection of NBQX was usually accompanied by a pronounced slowing in the time course of the EPSPs. On average, the EPSP rise times and half-widths were increased by 269 and 37%, respectively. This is most probably due to a considerable spatial spread of the synaptic contacts along the dendrites of motoneurones, with the most proximal synaptic contacts (producing the briefest synaptic potentials) subjected to a greater reduction in amplitude due to a higher local antagonist concentration. 5. An equivalent dendritic cable model of the motoneurone was used to interpret the observed changes in the time course of single fibre EPSPs. The time course of control single fibre EPSPs examined in the present study could be well matched using the cable model and assuming a single location for synaptic input. The observation of a slowed EPSP time course following antagonist ejection indicated that this assumption was not correct and that there was in fact considerable spatial spread in the synaptic contacts arising from these single afferent fibres. These results provide direct evidence that spatial spread of synaptic input may not be detected using the time course of a synaptic potential in conjunction with a neuronal cable model of the postsynaptic cell.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1991

A serial section electron microscope study of an identified Ia afferent collateral in the cat spinal cord.

Serial section electron microscopy has been used to examine a horseradish peroxidase (HRP)-labelled group Ia afferent collateral from its entry point in the grey matter to its termination in Clarke's column of the cat spinal cord. A wide range of geometries and myelination patterns were identified along the collateral, including 1) nodes specialized to exhibit a single synaptic bouton, 2) nodes specialized to exhibit two or more synaptic boutons connected by fine, unmyelinated lengths of the collateral, 3) terminal heminodes, along which boutons were separated by unmyelinated branches, and 4) complex arrangements along which myelinated and unmyelinated branches gave rise to one or more boutons. Thirty-six synaptic boutons of varied shape and size were exhibited by this collateral. Previous studies have shown that the geometry, branching, and myelination pattern of an axon play an important role in determining the amplitude and duration of an action potential propagating along that axon. In turn, the amplitude and duration of a presynaptic action potential influence the efficacy of transmitter release. The varied axonal geometries and myelination patterns observed in the present study provide further evidence in support of our previous proposal that there may be considerable nonuniformity in the efficacy of synaptic transmission among release sites arising from the same primary afferent fiber.

Afferent Pathways↗

PubMed1991

Calcium facilitation of group Ia EPSPs evoked in cat spinal motoneurones in vivo.

The extracellular environment of motoneurones in the cat spinal cord in vivo was altered by means of local perfusion of the central canal. Intracellular recordings were made to determine the effects of raised extracellular Ca2+ or Mg2+ concentration on the monosynaptic afferent excitatory postsynaptic potential (EPSP). Raised extracellular Mg2+ concentration reversibly reduced the EPSP amplitude, whereas raised extracellular Ca2+ concentration produced extremely large increases in the monosynaptic EPSP amplitude, up to almost an order of magnitude. In some cases, a reduction in amplitude of the EPSP and a delay in its onset were also observed, following raised extracellular Ca2+ concentration. This effect was thought to be due to a divalent cation block of the presynaptic action potential. A major conclusion from this study is that group Ia afferent terminals have a much greater transmitter release capacity than suggested by previous studies at this connection.

Animals↗