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Statistical model of the hippocampal CA3 region II. The population framework: model of rhythmic activity in the CA3 slice.

A statistical model is given to describe the electrical activity patterns of large neural populations of the hippocampal CA3 region. A continuous model has been formalized to describe the statistical processes governing the interactions within and between neural fields. The system of partial differential equations contains diffusion terms which determine the evolution of second moments of the probability distribution functions. The model is supplemented with a differential description of post-synaptic potentials. The discretization procedure has been designed so as to make the discrete equations scaling invariant. Population activities as well as underlying single-cell voltages are simulated during normal and epileptiform activities in the hippocampal CA3 slice. It is demonstrated that our model can reproduce electrophysiological phenomena characteristic to both single-cell and population activities. Specifically, fully synchronized population bursts, synchronized synaptic potentials, and low amplitude population oscillation were obtained.

Action Potentials↗

Voltage-clamp analysis of taurine-induced suppression of excitatory postsynaptic potentials in frog spinal motoneurons.

1. The depressant actions of taurine applications on lumbar motoneurons in the isolated frog spinal cord were studied using conventional intracellular recordings and the two-electrode voltage-clamp technique. 2. With microelectrodes containing K+-acetate, 0.75-2 mM taurine mostly induced a hyperpolarization that often faded or turned into depolarization during the continuous application. A higher concentration (5-7.5 mM) depolarized a majority of cells. The effects on the membrane potential were associated with an increase in input conductance (approximately 285%). 3. The reversal potential of the taurine-induced currents was approximately -70 mV, with microelectrodes containing K+-acetate. In recordings using KCl-filled electrodes, taurine (less than or equal to 2 mM) produced a large depolarization (greater than or equal to 20 mV) at resting potentials near -50 mV, thereby indicating that the reversal potential was positively shifted by loading the cell with Cl-. These results suggest that the taurine potentials were mediated predominantly by an increased Cl- permeability. 4. Voltage-dependent relaxations of taurine currents were observed in 10 of 14 neurons. 5. A linear relation was found between the input conductance and the amount of current required to generate a 1-mV increment in EPSP at resting potential. 6. Polysynaptic excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were more susceptible to taurine than the monosynaptic responses. Taurine (less than 1 mM) seemed to suppress the interneurons mediating polysynaptic pathways. 7. Monosynaptic EPSPs and EPSCs were decreased with higher concentrations of taurine (greater than 1 mM). The percent reduction of EPSPs and that of the corresponding EPSCs had a positive correlation (r = 0.95), whereas, there was no significant correlation between changes in EPSPs and in input conductance, and between changes in EPSCs and in input conductance. The amount of current required to produce a 1-mV increment of EPSP was increased in the presence of taurine, in association with the increased input conductance. 8. Taurine suppressed synaptic potentiation of EPSPs evoked by paired stimuli, at an interval of 60-180 ms. Gamma-D-glutamylglycine, an antagonist of receptors for excitatory amino acids, greatly reduced the amplitude of EPSPs, but had little effect on synaptic potentiation. 9. Taurine suppressed glutamate currents evoked at membrane potentials, clamped near rest in low Ca2+, high Mg2+ solution. 10. These findings suggest that the taurine-induced reduction of EPSPs is due mainly to suppression of EPSCs, through both presynaptic and postsynaptic mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Lemniscal and non-lemniscal synaptic transmission in rat auditory thalamus.

1. The central auditory pathway linking the inferior colliculus (IC) and the medial geniculate body (MGB) of the thalamus consists of a segregated ventral lemniscal and dorsal non-lemniscal projection whose synaptic transmission mechanisms remain unknown. Extracellular and intracellular recordings combined with axonal tract tracing and cell staining were made from lemniscal and non-lemniscal divisions of adult rat MGB maintained acutely in in vitro explants containing parallel tectothalamic projections. 2. Biocytin deposition within the brachium of the IC revealed dense axonal fibres projecting to the MGB. Thin axonal terminals were found throughout the ventral (MGv) and dorsal (MGd) divisions of the MGB. Bushy cells with tufted or bitufted dendritic branches were primarily found in the MGv. In the MGd, cells were mainly seen as stellate neurones having a radiate dendritic arbor. 3. Electrical stimulation of the brachium of IC invariably elicits fast, excitatory synaptic potentials in both MGv and MGd cells. The evoked responses occurred monosynaptically and were exclusively mediated by glutamate acting on both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Non-lemniscal MGd neurones recorded extracellularly exhibited a strong tendency to discharge in bursts in response to brachium stimulation. In contrast, a large proportion of ventral lemniscal cells tended to discharge in single or dual spikes. Intracellularly, MGd cells, but not MGv cells, showed a predominant, slow synaptic potential mediated by NMDA receptors. 4. It is concluded that the central auditory circuitry linking the tectum and the thalamus is connected monosynaptically via glutamatergic synapses. Lemniscal and non-lemniscal thalamic neurones possess distinct response properties which cannot be accounted for by a differential transmitter system or polysynaptic delays as postulated previously.

Animals↗

Potentiation of quantal secretion by insulin-like growth factor-1 at developing motoneurons in Xenopus cell culture.

Although evidence suggests that insulin-like growth factor (IGF) plays an important role in the development and growth of the nervous system, the effect of IGF-1 in the regulation of neurotransmitter release in the peripheral nervous system remains unknown. Here we show that acute application of IGF-1, a factor widely expressed in developing myocytes, dose-dependently enhances the spontaneous acetylcholine (ACh) secretion at developing neuromuscular synapses in Xenopus cell culture using whole-cell patch clamp recording. We studied the role of endogenously released IGF-1 by examining the effect of IGF-1 antibody on the frequency of spontaneous synaptic currents (SSCs) at high-activity synapses, and found SSC frequency was markedly reduced at these high-activity synapses. The IGF-1-induced synaptic potentiation was not abolished when Ca2+ was eliminated from the culture medium or there was bath-application of the pharmacological Ca2+ channel inhibitor Cd2+, indicating that Ca2+ influxes through voltage-activated Ca2+ channels are not required. Application of membrane-permeable inhibitors of inositol 1,4,5-trisphosphate (IP3) or ryanodine receptors effectively occluded the increase of SSC frequency elicited by IGF-I. Treating cells with the phosphoinositide-3 kinase (PI3-K) inhibitors wortmannin or LY294002, and with phospholipase Cgamma (PLCgamma) inhibitor U73122, but not the inhibitor of mitogen-activated protein (MAP) kinase PD98059, abolished IGF-1-induced synaptic potentiation. Taken collectively, these results suggest that endogenously released IGF-1 from myocytes elicits Ca2+ release from IP3- and/or ryanodine-sensitive intracellular Ca2+ stores of the presynaptic nerve terminal. This is done via PI3-K and PLCgamma signalling cascades, leading to an enhancement of spontaneous transmitter release.

Animals↗

A lower bound on the detectability of nonassociative learning in the local bending reflex of the medicinal leech.

Studies of neural mechanisms of learning and memory have focused on large changes at identified synapses. However, memory in distributed processing reflexes could involve widely distributed engrams characterized by small changes at every synapse in the network. To investigate this possibility, we used a neural network optimization algorithm to construct distributed engrams for nonassociative conditioning in a model of the local bending reflex of the medicinal leech (Hirudo medicinalis). The model comprised 4 sensory neurons, 10 to 40 interneurons, 8 motor neurons, and up to 480 connections. Synaptic connections in the model were first optimized to reproduce the amplitude and time course of motor neuron synaptic potentials recorded during local bending. This network, which represented the naive state before conditioning, was then reoptimized to the habituated or sensitized state. Following reoptimization, the memory for nonassociative learning was encoded by small changes dispersed across the entire network, and each change made only a small contribution to the learning. Moreover, because the changes were small, resolution of a few tenths of a millivolt, or 3-5% of an average synaptic potential, would be needed to account for half of the nonassociative learning. These results show how difficult distributed engrams can be to detect and provide a likely lower bound on the detectability of nonassociative learning in this and related networks.

Animals↗

Physiological consequences of morphologically detectable synaptic plasticity: potential uses for examining recovery following damage.

A growing literature indicates that brain structure is modified in various ways with experience. In this paper we briefly survey evidence that the brain retains the capacity to modify its organization in response to demands, including demands resulting from learning, throughout the lifetime. We attempt to address whether these experience-induced changes are accompanied by physiological changes that indicate a functional reorganization of the brain. The kinds of morphological changes that have been observed following brain injury appear to be very similar to those seen after learning. The similarity suggests that many of the basic mechanisms of synaptic change in the brain may be utilized for both functions. This suggests that we can take advantage of some of the methods used to test the changes in physiology with behavioral manipulations to examine the damaged brain. We advocate utilizing electrophysiological techniques to measure functional recovery from brain injury as these may be useful in evaluating both spontaneous recovery from damage and the therapeutic benefits of training, or other therapies.

Adaptation, Physiological↗

Re-innervation of guinea-pig superior cervical ganglion cells by preganglionic fibres arising from different levels of the spinal cord.

1. The ability of preganglionic axons to re-establish their normal pattern of synaptic connexions with superior cervical ganglion cells has been studied after section of the cervical sympathetic trunk.2. In vivo stimulation of the last cervical (C8) and the first seven thoracic ventral roots (T1-T7) 3-4 months after section of the trunk produced end-organ responses similar to those observed in normal animals.3. The pattern of innervation of individual neurones, determined by intracellular recording of synaptic potentials 4-9 months after cutting the sympathetic trunk, was also similar to that observed in normal neurones. Both normal and re-innervated ganglion cells were contacted by pre-ganglionic axons arising from C8 to T7, and each neurone was usually innervated by a contiguous subset of these segments.4. Re-innervated neurones, as normal cells, were typically dominated by the innervation from a particular spinal cord segment, with the adjacent segments contributing a synaptic influence that decreased as a function of distance from the dominant segment. This was true whether the amplitude of the post-synaptic potential, or the estimated number of contributing axons, was used as the criterion of segmental dominance.5. Re-innervated neurones, however, showed some abnormalities. The average number of ventral roots contributing innervation to each neurone was reduced from 4.1 to 3.0, and discontinuities in the sequence of innervating segments were more frequent than in normal neurones. Moreover, fewer preganglionic axons contacted each neurone after regeneration.6. A further difference between normal and re-innervated neurones during the period covered by these experiments was that axons from the more caudal spinal cord segments were less successful in re-establishing contacts with ganglion cells than those from the rostral segments. The more caudal the position of the preganglionic neurones, the more pronounced was this relative deficiency.7. Although anomalies of ganglion cell innervation were apparent, the basis for the restoration of normal functional effects appears to be the re-establishment of a pattern of innervation of individual neurones similar to that observed in normal ganglia.

Action Potentials↗

Long-term potentiation as synaptic dialogue.

We have proposed a testable model of the physiological and biochemical events underlying LTP that offers the following novel features. (1) The focus is not on a single mechanism or synaptic site, but rather on the integration and interaction of mechanisms occurring on both sides of the synapse, (2) beta PKC plays a critical presynaptic role in LTP, while gamma PKC functions postsynaptically. (3) These stages can be ordered in a time-delimited sequence of post- then presynaptic molecular events based on the period of effectiveness of inhibitor compounds. (4) The distinction is made between the time when kinase activation occurs and the time when the potentiated response requiring this kinase activation is observed.

Animals↗

The afferent volleys responsible for spinal proprioceptive reflexes in man.

1. To define the neural volleys responsible for the Achilles tendon jerk and the H reflex, muscle afferent activity was recorded using micro-electrodes inserted percutaneously into appropriate fascicles of the tibial nerve in the popliteal fossa.2. The response of soleus muscle afferents to tendon percussion consisted of a dispersed volley, starting 3.5-7.0 ms after percussion, increasing to a peak over 6.5-11.0 ms, and lasting 25-30 ms, depending on the strength of percussion. Electrical stimuli to the sciatic nerve at a level adequate to evoke an H reflex but subthreshold for the M wave produced a more synchronized volley, the fastest fibres of which had conduction velocities of 62-67 m/s, and the slowest 36-45 m/s.3. The wave of acceleration produced by percussion subthreshold for the ankle jerk spread along the skin at over 150 m/s. Midway between the bellies of the gastrocnemii it consisted of a damped oscillation with four to five separate phases and maximum amplitude approximately one-twentieth of that recorded on the Achilles tendon.4. With ten primary spindle endings, tendon percussion subthreshold for the ankle jerk elicited two to five spike discharges per tap, the shortest interspike intervals being 4-7 ms. Tendon percussion elicited single discharges from two Golgi tendon organs, and altered the discharge pattern of a single secondary spindle ending. The degree of dispersion of the multi-unit muscle afferent volley can be explained by the pattern of discharge of primary spindle endings.5. Percussion on the Achilles tendon evoked crisp afferent volleys in recordings from nerve fascicles innervating flexor hallucis longus, tibialis posterior, the intrinsic muscles of the foot and the skin of the foot. Electrical stimuli delivered to the tibial nerve in the popliteal fossa at a level sufficient for the H reflex of soleus produced either a volley in muscle afferents from the intrinsic muscles of the foot or a volley in cutaneous afferents from the foot.6. For comparable stimuli in the two positions, the H reflex was inhibited but the Achilles tendon jerk enhanced when the ankle was dorsiflexed from 105 degrees to 90 degrees .7. The duration of the rise times of the excitatory post-synaptic potentials (e.p.s.p.s) produced in soleus motoneurones by electrical stimulation, and by tendon percussion subthreshold for the H reflex and the ankle jerk respectively, was estimated from post-stimulus time histograms of the discharge of voluntarily activated single motor units in soleus. The mean e.p.s.p. rise times were 1.9 ms for electrical stimulation and 6.6 ms for tendon percussion. There was evidence that the duration of the electrically evoked e.p.s.p. was curtailed by an inhibitory post-synaptic potential (i.p.s.p.) of only slightly longer latency than the e.p.s.p.8. The mechanically induced and electrically induced afferent volleys are not homogeneous volleys in group I a afferents from triceps surae. The afferent volleys differ in so many respects that it is probably invalid to compare the H reflex and tendon jerk as a measure of fusimotor activity. It is suggested that neither reflex can be considered a purely monosynaptic reflex.

Achilles Tendon↗

Re-innervation of ganglia transplanted to the neck from different levels of the guinea-pig sympathetic chain.

Thoracic and lumbar sympathetic ganglia from donor guinea-pigs were transplanted to the bed of an excised superior cervical ganglion in host animals. Homotopic transplants of superior cervical ganglia served as controls. In this way the same set of preganglionic axons (the cervical sympathetic trunk) was confronted with ganglia from different levels of the sympathetic chain. Re-innervation of the transplants was studied after 3-5 months. 1. Neurones in ganglia transplanted from different levels of the sympathetic chain were re-innervated to about the same over-all degree by the preganglionic axons of the host's cervical sympathetic trunk. Thus, the mean amplitude of post-synaptic potentials, the estimated number of innervating axons, and the number of spinal segments providing innervation to each neurone were similar in transplanted thoracic, lumbar and superior cervical ganglion cells. 2. Neurones in transplanted mid-thoracic ganglia, however, were re-innervated more frequently, and more strongly, by axons arising from more caudal thoracic segments than neurones in transplanted superior cervical ganglia. Stimulation of axons arising from the fourth thoracic spinal segment (T4), for example, elicited post-synaptic potentials that on average were twice as large in transplanted fifth thoracic ganglion cells as in transplanted superior cervical ganglion cells; conversely, axons arising from T1 re-innervated neurones in the superior cervical ganglion about 2-3 times more effectively than fifth thoracic ganglion cells. This difference in the re-innervation of the fifth thoracic and the superior cervical ganglion is in the same direction as (although less pronounced than) the normal difference in the segmental innervation of these ganglia. 3. Transplanted lumbar ganglia were also re-innervated more effectively by relatively caudal segments compared to re-innervated cervical ganglia, but this difference was no greater than that observed for transplanted thoracic ganglia. 4. We conclude that preganglionic axons can distinguish (or be distinguished by) ganglia derived from different levels of the sympathetic chain. Our findings are consistent with the view that ganglion cells have some permanent property that biases the innervation they receive.

Animals↗

Effect of oxidative stress on excitatory amino acid release by cerebral cortical synaptosomes.

Previous studies in our laboratory have suggested that an oxidation reaction is responsible for the actions of free radicals to decrease synaptic potentials. Recently we observed that free radicals both decreased depolarization-induced vesicular release and enhanced basal, nonvesicular release of the excitatory amino acid, [3H]L-glutamate. In order to evaluate the contribution of oxidative reactions to this latter effect, we evaluated the actions of the oxidizing agent chloramine-T on synaptosomal release of excitatory amino acids, using [3H]D-aspartate as the exogenous label. Basal and depolarization evoked [3H]D-aspartate release were calcium-independent and nonvesicular. Chloramine-T pretreatment significantly increased basal release, while having no effect on high K(+)-evoked release. These data suggest that an oxidative process can mimic the free radical increase of basal release, as well as the decrease in synaptic potentials. On the other hand, the calcium-independent-evoked release may involve a different mechanism. Our results demonstrate that under basal, nondepolarizing conditions, oxidative stress exerts an adverse effect on the presynaptic nerve terminal, resulting in an increased release of potentially damaging excitatory amino acid neurotransmitters.

Amino Acids↗

Ia afferent excitation of motoneurones in the in vitro new-born rat spinal cord is selectively antagonized by kynurenate.

Intracellular recordings from motoneurones in in vitro preparations of new-born rat spinal cord were used to study the sensitivity of the Ia excitatory post-synaptic potential (e.p.s.p.) to antagonists of excitatory amino acids, in order to test whether group Ia primary afferents release L-glutamate, or a similar compound, as a neurotransmitter. The Ia e.p.s.p. was isolated for study by using low intensity stimulation of individual muscle nerves and by the addition to the superfusate of high concentrations of divalent cations which suppressed polysynaptic inputs to the motoneurones. The pattern of convergence of group Ia afferents from homonymous, heteronymous and antagonist muscle nerves onto motoneurones in the new-born rat was similar to that reported in the adult cat spinal cord. Homonymous muscle nerve stimulation evoked the largest amplitude Ia e.p.s.p.s while heteronymous muscle nerve stimulation elicited smaller e.p.s.p.s or had no effect. Stimulation of antagonist muscle nerves resulted in inhibitory post-synaptic potentials (i.p.s.p.). Superfusion of the specific N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovalerate, did not inhibit the Ia e.p.s.p. but did suppress later, polysynaptic components of the response evoked from dorsal roots. Kynurenate was a potent inhibitor of the Ia e.p.s.p. The site of action of kynurenate was examined by observing its effect on synaptic depression and was found to be consistent with a post-synaptic mechanism. Kynurenate selectively blocked the depolarization of motoneurones elicited by L-glutamate and had no effect on the depolarization evoked by carbachol. The selectivity of action of kynurenate was further examined by comparing its effect on the recurrent i.p.s.p. evoked by ventral root stimulation with its effect on the Ia e.p.s.p. The recurrent i.p.s.p. was antagonized by strychnine and dihydro-beta-erythroidine while kynurenate, at a concentration which greatly reduced the Ia e.p.s.p., had no effect. These results suggest that stimulation of group Ia primary afferents evokes the release of L-glutamate, or a similar compound, which activates non-NMDA excitatory amino acid receptors on motoneurones which, in turn, mediate the Ia e.p.s.p.

2-Amino-5-phosphonovalerate↗

Group Ia synaptic input to fast and slow twitch motor units of cat triceps surae.

1 The characteristics of the group Ia synaptic input to triceps surae motoneurones have been examined in pentobarbitone-anaesthetized cats, using intracellular recording techniques. The mechanical properties of the muscle units innervated by the cells were determined and the motoneurone input resistance values were also measured.2. A significant positive correlation was found between the maximum amplitudes of homonymous composite (electrically evoked) monosynaptic excitatory post-synaptic potentials (EPSPs) and the motoneurone input resistance values across the entire population of units sampled. The same correlation in the case of heteronymous EPSPs was also significant although somewhat less strong.3. The distribution of the amplitudes of unitary miniature EPSPs (mEPSPs) of presumed group Ia origin, elicited by small static stretches of the homonymous muscles, were also studied. A significant positive correlation was found between the median amplitudes of the mEPSP distributions and the input resistance values in the motoneurones studied. Positive correlation was also observed between the amplitudes of the median mEPSPs and the maximum homonymous composite EPSPs in the cells for which both data points were available.4. In each of these correlations, the synaptic potential amplitudes tended to be larger in the relatively high resistance type S (slow twitch muscle unit) motoneurones from both gastrocnemius and soleus motor pools, than in the lower resistance type F (fast twitch muscle unit) gastrocnemius cells.5. Examination of the shape of the homonymous monosynaptic EPSP wave forms in different motoneurones showed that these tended to be significantly longer in duration in type S cells than in type F. This difference could not be entirely accounted for by the relatively small difference in mean time constant values found in types F and S cells.6. The results suggest that the density of group Ia synaptic terminals tends to be higher on type S motoneurones than on the type F cells. Further, cells receiving a relatively high density of group Ia input apparently tend to have a greater proportion of this input distributed to distal membrane regions than is the case in motoneurones receiving a relatively low input density.

Animals↗

Effects on iontophoretically applied acetylcholine on membrane potential and synaptic activity of bulbar respiratory neurones in decerebrate cats.

Intracellular recordings were made from bulbar respiratory neurones of decerebrate cats, together with iontophoretic application of acetylcholine and its specific antagonists to assess cholinergic mechanisms involved in the central respiratory network in vivo. Of 126 respiratory-related neurones impaled in the ventral respiratory group, iontophoresis of acetylcholine produced depolarization in 67 cells (53%), hyperpolarization in 36 cells (29%), and no effect in the remaining 23 cells (18%). Depolarization occurred predominantly in laryngeal motoneurones (31/40) and bulbo-spinal neurones (4/5), while a comparable number of non-antidromically-activated respiratory neurones displayed either depolarization (33/81) or hyperpolarization (31/81). Acetylcholine had no significant effect on excitatory and inhibitory postsynaptic potentials in all types of neurones tested. Both depolarizing effects of acetylcholine were antagonized by co-iontophoresis of atropine, but not by hexamethonium. Input resistance was increased (7/9) or unchanged (2/9) in depolarized cells, whereas it was unaltered in all hyperpolarized cells tested (n = 6). The present results suggest that the distribution and functions of cholinergic muscarinic receptors are different for the laryngeal and bulbo-spinal types of respiratory neurones and the non-antidromically-activated respiratory neurones in the cat.

Acetylcholine↗

A novel role for calcium-independent phospholipase A in alpha-amino-3-hydroxy-5-methylisoxazole-propionate receptor regulation during long-term potentiation.

A considerable body of evidence indicates that phospholipase A(2) (PLA(2)) enzymes participate in long-term potentiation (LTP) of excitatory synaptic transmission. In the present study, we have undertaken experiments to identify which calcium-independent isoform of PLA(2) is involved in synaptic plasticity and to determine whether calcium-independent PLA(2) (iPLA(2)) contributes to post-synaptic processes of LTP. Using field recordings from rat CA1 hippocampal slices, we found that theta-burst stimulation (TBS)-induced LTP of field excitatory post-synaptic potentials (fEPSPs) was abolished by the iPLA(2) inhibitor bromoenol lactone (BEL) but not by the Ca(2+)-dependent PLA(2) inhibitor arachidonyl trifluoromethyl ketone (AACOCF(3)). The ionic currents generated during TBS were not affected during iPLA(2) inhibition as BEL by itself had no effect on the magnitude of facilitation during burst responses. In addition, (R)-BEL, an enantioselective inhibitor of iPLA(2)gamma, precluded TBS-induced LTP, an action that was not replicated by the iPLA(2)beta inhibitors (S)-BEL and methyl arachidonyl fluorophosphonate. (R)-BEL was, however, ineffective on pre-established LTP. Finally, BEL also prevented the potentiation of fEPSPs elicited by brief exposure to 50 microM N-methyl-d-aspartate, as well as the associated up-regulation of alpha-amino-3-hydroxy-5-methylisoxazole-propionate (AMPA) receptor GluR1 subunit levels and the increase of (3)H-AMPA binding in crude synaptic fractions. Collectively, these results unravel a new role for iPLA(2)gamma in LTP, which appears to favor the insertion of AMPA receptors at post-synaptic membranes.

Animals↗

Synchronous afferent discharge from a passive muscle of the cat: significance for interpreting spike-triggered averages.

Evidence is presented for the existence of synchrony between the spike trains of muscle afferents of the passive cat medial gastrocnemius muscle held at fixed length. Synchrony between the spike trains of a population of muscle afferents was quantified by means of a synchronization index (Is), derived from spike-triggered averages of the muscle-nerve neurogram and the rectified neurogram. A previously used test based solely upon the neurogram average (Watt, Stauffer, Taylor, Reinking & Stuart, 1976) is shown to be invalid. The differences between experimentally derived Is values and theoretical Is values derived for the condition of asynchrony were compared to estimated confidence limits for those differences. This comparison revealed that twenty-two of fifty-three muscle-afferent spike trains whose rectified averages satisfied certain conditions for interpreting the Is were synchronized with the discharge of other afferents. The form of the rectified averages of another eight afferents suggested that these afferents might also have been synchronized. Synchrony in the discharge of muscle afferents was found in three experiments in which the neurogram was recorded from a single nerve branch to medial gastrocnemius, as well as in the data of experiments in which the whole muscle nerve was used. The degree of synchrony was similar for Ia, spindle group II and Ib afferents. The magnitude of the synchrony found in these experiments was judged by comparison to the results of analog simulations and the increase in Is values resulting from the application of small, quick stretches to the medial gastrocnemius muscle. The degree of synchrony found on average was approximately equivalent to that of a single spike occurring once for every four discharges of the reference spike train. Simulations were performed to determine the distortion of monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) obtained by spike-triggered averaging which would be produced by synchrony between the spike trains of Ia and spindle group II afferents of the magnitude found in this study. These simulations indicate that the apparent amplitude would be increased by approximately 4 microV on average. Both the 10-90% rise time and the half-width would increase, the effects being greater for smaller e.p.s.p.s. Consequently, the synchrony found in this study is of most concern in the study of small post-synaptic potentials, such as those due to spindle group II afferents.

Action Potentials↗

Muscarinic and peptidergic excitation of bull-frog sympathetic neurones.

The large B cells of bull-frog sympathetic ganglia are well known to be depolarized by slow synaptic transmission, muscarinic agonists, analogues of luteinizing hormone-releasing hormone (LHRH), and substance P. Voltage-clamp analysis shows that these actions result from two underlying mechanisms: inhibition of the M-current, a voltage-dependent potassium current; and in some cells, an inward current associated with an increase in conductance. The additional inward current appears as a voltage-insensitive change in the instantaneous conductance (i.e. apparent leak conductance). The additional inward current is typically slower in onset and offset than is M-current inhibition. It is typically seen for higher concentrations and longer durations of agonist application. In many cells, only a decrease in M-current can be demonstrated. Muscarine inhibits the M-current with 50% inhibition (I50) at 0.7 microM. At least 86% of the M-current is muscarine sensitive. At comparable concentrations, oxotremorine produces less M-current inhibition than does muscarine. Some analogues of teleost LHRH (T-LHRH) are more potent as M-current inhibitors than T-LHRH itself. Those peptides tend to act more slowly than T-LHRH. Substance P shows variable potency for M-current inhibition, with I50 s ranging from 2 nM to greater than 2 microM on different cells. The response to long applications of substance P desensitizes in some cells, which has not been observed for comparable applications of muscarinic or LHRH agonists. Other tachykinins (including substance K) inhibit the M-current. C-terminal fragments of substance P are ineffective, and M-current inhibition by substance P is not blocked by [D-Pro2,D-Trp7,9]- or [D-Arg1,D-Pro2, D-Trp7,9,Leu11] substance P. The slow muscarinic excitatory post-synaptic potential (e.p.s.p.) produces a graded inhibition of up to 90% of the M-current. Occasional cells show an additional inward current with an associated increase in conductance during the slow e.p.s.p. This effect is less marked than with exogenous muscarinic agonists. The late, slow e.p.s.p., which is produced by stimulation of high threshold C-fibre inputs and is resistant to cholinergic antagonists, also involves M-current inhibition. An additional inward current can be observed in some cells. M-current inhibition (by agonists or slow synaptic potentials) increases the number of spikes produced by a given depolarizing current, often allowing maintained firing. This action is not mimicked by equivalent depolarization, and is still seen when the cell is manually clamped to the original resting potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Distributed processing by visual interneurons of crayfish brain. I. Response characteristics and synaptic interactions.

1. The visual responses and synaptic interactions of a small population of crayfish interneurons are described. 2. The discharge of optic nerve sustaining fibers (tonic on-cells) appears in the brain prior to the onset of the light-evoked discharge of any of the higher order, descending visual interneurons. Direct depolarization of impaled sustaining fibers elicits impulse responses in a large number of descending interneurons. These results indicate that the sustaining fibers provide the visual input to higher order interneurons. 3. Four classes of descending interneurons can be distinguished. All arise in the brain and have axons in the circumesophageal connectives. The response forms vary from tonic to phasic. Two classes of tonic cells are distinguished by response latency and two classes of phasic neurons are distinguished by the rate of response adaptation. The phasic neurons exhibit the most rapid habituation, the largest receptive fields, and the most potent nonvisual inputs. 4. Synaptic interactions are studied by cross-correlation of impulse trains and direct observation of synaptic potentials. About 84% of the cells examined reveal evidence of functional connections to other descending visual interneurons. 5. Cross-correlograms derived from impulses of parallel interneurons exhibit a mean time lage to peak of 6.6 +/- 2.8 ms (SD). The measured delay from EPSP onset to spike onset is 6.0 +/- 4.0 ms. Thus a substantial proportion of the correlogram's time lag to peak is associated with postsynaptic integration time. 6. Direct depolarization of impaled tonic on-cells elicits impulse activity at a fixed delay in other descending interneurons. 7. Synaptic potentials in descending visual interneurons are correlated 1:1 with axon spikes of other descending interneurons. 8. A third of the 80 interactions examined were reciprocal and many cells were implicated in multiple interactions. 9. The results suggest that the descending visual interneurons are organized in a complex network, which can cordinate the discharge of various subpopulations of the ensemble. It is proposed that the coordination of impulses in parallel interneurons may be a mechanism for coding and information transfer in the crayfish nervous system.

Animals↗