Search PubMed⌕ Search

Biomedical subjects

Y Yarom

Publications and source records attributed to Y Yarom.

At least 55 records · Page 3Linked to original sources

Voltage behavior along the irregular dendritic structure of morphologically and physiologically characterized vagal motoneurons in the guinea pig.

1. Intracellular recordings from neurons in the dorsal motor nucleus of the vagus (vagal motoneurons, VMs) obtained in the guinea pig brain stem slice preparation were used for both horseradish peroxidase (HRP) labeling of the neurons and for measurements of their input resistance (RN) and time constant (tau 0). Based on the physiological data and on the morphological reconstruction of the labeled cells, detailed steady-state and compartmental models of VM were built and utilized to estimate the range of membrane resistivity, membrane capacitance, and cytoplasm resistivity values (Rm, Cm, and Ri, respectively) and to explore the integrative properties of these cells. 2. VMs are relatively small cells with a simple dendritic structure. Each cell has an average of 5.3 smooth (nonspiny), short (251 microns) dendrites with a low order (2) of branching. The average soma-dendritic surface area of VMs is 9,876 microns 2. 3. Electrically, VMs show remarkably linear membrane properties in the hyperpolarizing direction; they have an average RN of 67 +/- 23 (SD) M omega and a tau 0 of 9.4 +/- 4.1 ms. Several unfavorable experimental conditions precluded the possibility of faithfully recovering ("peeling") the first equalizing time constant (tau 1) and, thereby, of estimating the electrotonic length (Lpeel) of VMs. 4. Reconciling VM morphology with the measured RN and tau 0 through the models, assuming an Ri of 70 omega.cm and a spatially uniform Rm, yielded an Rm estimate of 5,250 omega.cm2 and a Cm of 1.8 microF/cm2. Peeling theoretical transients produced by these models result in an Lpeel of 1.35. Because of marked differences in the length of dendrites within a single cell, this value is larger than the maximal cable length of the dendrites and is twice as long as their average cable length. 5. The morphological and physiological data could be matched indistinguishably well if a possible soma shunt (i.e., Rm, soma less than Rm, dend) was included in the model. Although there is no unique solution for the exact model Rm, a general conclusion regarding the integrative capabilities of VM could be drawn. As long as the model is consistent with the experimental data, the average input resistance at the dendritic terminals (RT) and the steady-state central (AFT----S) and peripheral (AFS----T) attenuation factors are essentially the same in the different models. With Ri = 70 omega.cm, we calculated RT, AFS----T, and AFT----S to be, on the average, 580 M omega, 1.1, and 13, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Low threshold calcium spikes, intrinsic neuronal oscillation and rhythm generation in the CNS.

Field potential studies in vivo have shown that many subcortical structures, such as the inferior olivary nucleus, the thalamic nuclei and the lateral habenular nucleus, generate behaviorally relevant rhythms. In each region, intracellular analysis in brain slices has revealed that activation of a transient, low-threshold calcium current plays a pivotal role in rhythmogenesis. The membrane potential of each individual neuron may oscillate rhythmically as a result of interplay between this current and other inward and outward voltage and calcium-dependent currents. Synchronization of this oscillatory single-cell activity, through mutual interaction and/or appropriately timed afferent drive, results in generation of stereotyped population rhythms.

Action Potentials↗

Electrophysiology of degenerating neurones in the vagal motor nucleus of the guinea-pig following axotomy.

1. The electrophysiological properties of motoneurones in the dorsal motor nucleus of the vagus in the guinea-pig were studied at different times following cervical vagotomy. The results were compared both to normal neurones and to results obtained at the same time from intact neurones located in the contralateral nucleus. 2. The input resistances of axotomized neurones are significantly higher than those of normal neurones (66 +/- 29 compared to 45 +/- 17 M omega). This difference was seen during the first month following axotomy without any sign of a time-dependent process. On the other hand, no change in resting potential was observed. 3. Significant reduction in action potential amplitude was observed 1 month after axotomy (from 97.8 +/- 8 to 87 +/- 7 mV) and was followed by slow recovery lasting more than 1 year. Neither the Na+ conductance nor the voltage-dependent K+ conductance responsible for the fast rise and fall of the action potential, respectively, were affected by axotomy. 4. One month after axotomy the action potential duration in axotomized neurones was found to be shorter than that of normal neurones (0.9 +/- 0.1 ms compared to 1.1 +/- 0.04 ms). We show that this decrease in duration reflects a reduction in the depolarizing hump on the falling phase of the action potential, which is known to express the Ca2+ conductance activated during the action potential. A slow recovery of the spike duration was observed, although an age-dependent reduction in duration was also observed in neurones in the contralateral nucleus. 5. Two K+ conductances, the Ca2+-dependent and the A type, decrease 1 month after axotomy and follow a similar time course of recovery to that of the reduction in action potential duration and amplitude. 6. The firing pattern of axotomized neurones undergoes profound alteration, manifested as an increase in firing duration as a response to a rectangular current pulse. Examination of these alterations reveals that the reduction in both K+ conductances is responsible for the observed changes. 7. The results are discussed within the framework of the degenerative response known to take place in the nucleus following axotomy. We hypothesize that the observed phenomena reflect an increase in intracellular Ca2+ concentration which, in turn, inactivates the Ca2+ and K+ conductances. Furthermore this rise in intracellular Ca2+ may eventually be responsible for cell death.

Action Potentials↗

Time course and distribution of motoneuronal loss in the dorsal motor vagal nucleus of guinea pig after cervical vagotomy.

Cells in the dorsal motor vagal nucleus (DMVN) of the adult guinea pig were counted at different times after unilateral cervical section of the vagus nerve. The counts were made from serial 30 microns coronal sections throughout the DMVN in normal and operated animals. There are three types of cells in the DMVN of guinea pig: medium-sized motoneurons that are retrogradely filled by HRP from the site of the vagotomy, small neurons, and glial cells. An interesting observation was a change in distribution of cells in the DMVN with age in unoperated guinea pigs. Following vagotomy degeneration was seen only in the motoneurons. Disappearance of motoneurons was slow and only 27% were present after 1 year. During that time the decrease in the total number of motoneurons was exponential with a time constant of 8.6 months, but degeneration in different parts of the nucleus was not uniform. Thirty-four percent of motoneurons in the caudal area of DMVN disappeared in the first month after vagotomy, while the rostral area was almost unchanged. The rostral area, however, showed rapid degeneration between 3 and 6 months after vagotomy. The central part of the nucleus degenerated at a constant rate between those of the rostral and caudal regions. At the end of 1 year, cell loss in all parts of the nucleus was approximately equal. Surviving motoneurons showed morphological changes: rounding of the soma, continuous reduction of the cell volume, and shrinkage of the nucleus. Occasional abnormal forms showing vacuolization or invaginated nuclei were seen. Calculations show that the process of degeneration lasts 25 days on the average. The marked degeneration found in dorsal vagal motoneurons, in contrast to recovery from axotomy in somatic motoneurons, is similar to that found in intrinsic neurons of the central nervous system. The slow and continuous time course of disappearance of motoneurons after vagotomy, however, is exceptional. It is reasonable to postulate that the increased vulnerability of these motoneurons may be sufficient to result in degeneration in response to what are normally nonpathological metabolic demands.

Animals↗

Long-term modifiability of anomalous and delayed rectification in guinea pig inferior olivary neurons.

Delayed and anomalous rectification was studied in inferior olivary (I.O.) neurons in guinea pig brain stem slices maintained in vitro. Hyperpolarization of the I.O. cell beyond rest membrane potential was accompanied by anomalous rectification (AR). This consisted of 2 parts: an instantaneous and a time-dependent component. The "instantaneous" component was blocked by bath addition of Ba2+ or Cs+ and demonstrated inactivation following prolonged hyperpolarization. The time-dependent component, referred to as the gK(ol), was blocked by harmaline in concentrations of 0.1 mg/ml or by substitution of Co2+, Cd2+, or Mn2+ for Ca2+ in the bath. The gK(ol) was blocked by extracellular Cs+ but not by Ba2+. Delayed rectification (DR), consisting of 2 distinct components, was observed after membrane depolarization by more than 10 mV with respect to rest (usually at -65 mV). One of the components of the DR was found to be quite similar to the classical gK. It did not demonstrate significant inactivation with membrane potential change and was reduced by Ba2+ or tetraethylammonium (TEA). A second component of the DR demonstrated voltage-dependent inactivation and was thus referred to as gK(inact). This inactivation determined by current-clamp measurements had a sigmoidal time course, with approximately a 1 sec onset latency and a half-time to peak of 7 sec. The inactivation of gK(inact) outlasted current injection for tens of seconds to several minutes, depending on the duration and amplitude of the preceding depolarization. During this period, I.O. neurons could be easily activated and demonstrated full dendritic spikes following current injection or excitatory synaptic input that had previously been subthreshold for spike initiation. The inactivation component of the DR was removed by prolonged membrane hyperpolarization beyond rest. gK(inact) was blocked by 4-aminopyridine (4-AP; 100 microM) but not by Ba2+. This inactivation was dependent on the presence of extracellular Ca2+ or Ba2+. Addition of Co2+ or Cd2+ to the bath did not block gK(inact) but did prevent its inactivation. The modulatory effects of these different membrane conductances on the integrative properties of I.O. neurons are described. The long duration of the inactivation of DR and AR is considered as the basis for a dynamic long-term modulation of the electroresponsive and integrated properties of I.O. neurons.

4-Aminopyridine↗

Sodium-dependent regenerative responses in dendrites of axotomized motoneurons in the cat.

Ten days after extradural axotomy, partial spikes are found in greater than 20% of cat L7 motoneurons, while 15-21 days after axotomy the incidence increases to 60%. These responses are produced in excitable (hot) spots in the dendrites by synaptic excitation. Intracellular injection of QX-314, a lidocaine derivative and effective blocker of Na+ channels from within neurons, results in elimination of partial spikes before blocking somadendritic spikes. The action of QX-314 does not depend on changes in passive membrane properties or on changes in synaptic properties. Injections of Cs+ and Cl- ions rule out any major role for calcium, potassium, or chloride currents in the production of partial spikes. The partial spikes represent an unusual Na+-dependent dendritic phenomenon induced by axotomy when carried out relatively near the soma. It is reasonable to postulate that the partial spikes result from a higher concentration of Na+ channels in the dendrites. This may be the consequence of a high rate of production of Na+-channel proteins that are intended for the cut end of the axon; alternatively, they may result from the reflection from the cut end of such proteins produced at either a normal or an increased rate. These aberrant channels are inserted into somatic and dendritic membranes in higher concentrations than normal and, as well as producing local dendritic regions of low safety factor responsible for the partial spikes, also produce somadendritic spikes of unusually fast rise time and lower than usual threshold, which are relatively resistant to QX-314.

Action Potentials↗

Oscillatory properties of guinea-pig inferior olivary neurones and their pharmacological modulation: an in vitro study.

The oscillatory properties of the membrane potential in inferior olivary neurones were studied in guinea-pig brain-stem slices maintained in vitro. Intracellular double-ramp current injection at frequencies of 1-20 Hz revealed that inferior olivary neurones tend to fire at two preferred frequencies: 3-6 Hz when the cells were actively depolarized (resting potential less than -50 mV), and 9-12 Hz when they were actively hyperpolarized (resting potential more than -75 mV). In 10% of the experiments spontaneous subthreshold oscillations of the membrane potential were observed. These oscillations, which resembled sinusoidal wave forms and had a frequency of 4-6 Hz and an amplitude of 5-10 mV, occurred synchronously in all cells tested within the slice. These oscillations persisted in the presence of 10(-4) M-tetrodotoxin and were blocked by Ca2+ conductance blockers or by the removal of Ca2+ from the bathing solution. The oscillations were affected by gross extracellular stimulation of the slice but not by intracellular activation of any given neurone. The data indicate that these oscillations reflect the properties of neuronal ensembles comprised of a large number of coupled elements. Similar ensemble oscillation could be induced, in most experiments, by adding harmaline (0.1 mg/ml) and serotonin (10(-4) M) to the bath and could be blocked by bath addition of noradrenaline. Harmaline was found to increase cell excitability by hyperpolarizing the neurones and shifting the inactivation curve for the somatic Ca2+ spike to a more positive membrane potential level. The role inferior olivary oscillations play in the organization of motor coordination is discussed.

Action Potentials↗

Electrophysiological properties of guinea pig septal neurons in vitro.

The electrophysiological properties of septal neurons have been examined in vitro in guinea pig brain slices. These cells display different firing modes when stimulated by transmembrane current pulses depending on the amplitude of the depolarization. With small pulses septal neurons fire repetitive Na spikes but on larger depolarizations they respond with a single full-Na action potential which is followed by a number of spikes of smaller amplitude. A further increase in the amplitude of the pulse evokes powerful Ca spikes possibly generated in the dendrites. These Ca spikes appear with larger amplitude in presumptive intradendritic recordings. In many cells stimulation of the fimbria evoked postsynaptic responses consisting of either a depolarization, a hyperpolarization or a depolarization-hyperpolarization sequence.

Action Potentials↗

Intrinsic control of electroresponsive properties of transplanted mammalian brain neurons.

The present study presents the first analysis of neurons in mammalian brain transplants based on intracellular recording. The results, obtained in brain slices including both donor and host tissue, showed that neuronal precursor cells in embryonic transplants retained their ability to complete their normal differentiation of cell-type-specific electroresponsive properties. Distortions in cell aggregation and synaptic connectivity did not affect this aspect of neuronal differentiation.

Animals↗

Ionic currents and firing patterns of mammalian vagal motoneurons in vitro.

The electrophysiological properties of guinea-pig dorsal vagal motoneurons were studied in an in vitro slice preparation. Antidromic, orthodromic and direct stimulation of the neurons demonstrated that the action potential is comprised of several distinct components: a fast initial spike followed by afterdepolarization and an early and a late afterhyperpolarizations. The fast initial spike and the early afterhyperpolarization were blocked by tetrodotoxin and tetraethylammonium ions, respectively. The afterdepolarization (present on the falling phase of the spike) and the late afterhyperpolarization were blocked by the addition of ions known to block calcium conductance (CdCl2, CoCl2 or MnCl2), indicating close association between these two potentials. Prolonged outward current injection through the recording electrode produced two different firing patterns, depending on the initial level of the membrane potential. From resting potential (usually -60 mV) the firing pattern was characterized by a short train of action potentials appearing shortly after the onset of the depolarization step. By contrast, when the depolarization was delivered from a hyperpolarized membrane potential level, a short train of repetitive firing appeared after an initial delay of 300-400 ms. The membrane current responsible for this initial reduction in excitability was studied by means of a single-electrode voltage-clamp technique. The magnitude, direction and kinetics of such current flow are consistent with the presence of early potassium current (IA), partly inactive at the resting potential. Synaptic activation of vagal motoneurons could be obtained by electrical stimulation of the tissue surrounding the vagal nucleus or by direct activation of the vagal nerve. Perivagal stimulation generated excitatory and inhibitory synaptic potentials which could be reversed by shifting the membrane potential. Vagal nerve stimulation, in addition to the antidromic activation of the cells, generated depolarizing responses which were unitary in nature and did not show much sensitivity to shifts in membrane potential. Perivagal and vagal nerve-evoked depolarizations could generate action potentials as well as partial dendritic spikes. We conclude that spike electroresponsiveness in vagal motoneurons is generated by voltage-dependent Na+ and Ca2+ conductances. In addition, the Ca2+-dependent current triggers a K+ conductance which is responsible for modulating the firing frequency obtained from the normal resting level.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Intracellular injection of acetylcholine blocks various potassium conductances in vagal motoneurons.

Injection of acetylcholine into cholinergic neurons of the dorsal motor nucleus of the vagus induced membrane depolarization, an increase in input resistance, a decrease of early and late afterhyperpolarizations and a prolongation of the action potential. These effects were reversible and within 10-20 min almost complete recovery was always observed. Externally applied acetylcholine, even with doses as high as 15 mM, was not effective. Acetylcholine appeared to block voltage- and Ca2+-dependent K+ conductances. This block was manifested by the reduction of both the early and late afterhyperpolarizations and a decrease of the delayed rectification. The reversal potential for the conductance decrease was 15-30 mV negative to the resting potential. As a result of this blockade an increased Ca2+ current ensues, which is responsible for most of the prolongation of the action potential. The same responses were obtained after the injection of carbamylcholine, neostigmine and choline. However, unlike acetylcholine no sign of recovery was observed. In fact injection of neostigmine, carbamylcholine or neostigmine, together with acetylcholine, produced a delayed response which may reflect the accumulation of endogenous acetylcholine.

Acetylcholine↗

Neuronal interactions mediated by neurally evoked changes in the extracellular potassium concentration.

Neuronal interactions mediated by alteration of the extracellular K+ concentration [K+]o occur between populations as well as among single neurones in very restricted regions. The interactions mediated by K+ ions may range from low efficacy ones (in which the effects of increased [K+]o around the non-active cells can be recorded only after massive activity of a large population of neurones) to very effective interactions (in which a single action potential in a neurone is sufficient to produce a depolarization of several mV in a second one). Such efficient K+-mediated interactions cannot be unequivocally distinguished by shape, amplitude or time course from postsynaptic responses induced by chemical or electrotonic synapses. We review here experiments which demonstrate various levels of interactions mediated by changes in potassium ion concentration. The giant axons (Gax) and non-giant axons from the central nervous system of the cockroach Periplaneta americana were used. The types of interactions discussed are: pathological interactions among populations of neurones induced by the convulsant drug picrotoxin; restricted and limited interactions which are the consequence of the combination of the special geometry of Gaxs and increases in extracellular K+; and finally, local and efficient interactions among Gaxs which are postulated to be mediated by K+ ions. The experiments described in this review, as well as others, demonstrate that the extracellular spaces in the CNS serve as predetermined pathways for K+-mediated neuronal communication. When the extracellular space between two adjacent neurones is very small, the K+-mediated interaction may resemble the PSPs of chemical or electrotonic synapses. It is possible that because of this resemblance, other K+-mediated interactions in the CNS have not been identified as such.

Abdomen↗

Functional elimination of afferent pathways and decreased safety factor during postembryonic development of cockroach giant interneurons.

The giant interneurons (GIN) from the cockroach CNS undergo two major physiological changes during the postembryonic developmental period: (A) a marked decrease in the number of afferent pathways innervating the GIN at the metathoracic ganglion (Ts); and (B) a gradual decrease in the safety factor for impulse propagation along the intraganglionic segment in T3. In 100% of the experiments (n greater than 100) performed on GIN from early developmental stages, spontaneous postsynaptic potentials (SPSPs) were recorded; in adults, on the other hand. SPSPs have been recorded in only 34% of the experiments (n = 74). Evoked synaptic potentials can be elicited in nymphal stages by stimulation of 8 nerves of T3, the contralateral connectives, ipsi- and contralateral nerve roots 2, 3, 5, and by stimulation of adjacent GINs. In adult, PSPs can be evoked by stimulation of adjacent GINs, and contralateral thoracic connectives, but not from nerves 2, 3 and 5. The functional disappearance of synaptic inputs to the GINs does not reflect a general phenomenon of reduction in synaptic transmission efficacy. In previous studies it was demonstrated that high frequency stimulation of adult GIN leads to blockage of impulse propagation in T3. In nymphal stages, the safety factor for propagation of impulses along T3 is higher. The reduction in safety factor appears gradually during the postembryonic developmental period. From analysis of the mechanisms underlying the elimination of functional afferent pathways and the appearance of low safety factor (see consecutive paper by Yarom and Spira) it is concluded that the functional elimination of afferents is a consequence of decreased transmission efficacy, while the appearance of low safety regions for impulse propagation is a consequence of morphological changes of the GIN segment within ganglion T3.

Afferent Pathways↗

Morphological and electrophysiological properties of giant interneurons during the postembryonic development of the cockroach CNS.

The giant interneurons (GIN) of the central nervous system of the cockroach undergo two major physiological changes during the postembryonic development period: (A) a gradual decrease in the safety factor for action potential propagation across the GIN in the metathoracic ganglion (T3); and (B) a marked decrease in the number of afferent pathways innervating the GIN in T3 (Spira and Yarom). Analysis of the morphological structure of the GINs, by intracellular injection of cobalt ions and by cross-sections prepared for light and electron microscope, reveals that despite the extensive growth of the GINs during the postembryonic developmental period, the main structural outline of the fibers is not altered. In adult preparations, however, the GIN diameter narrows 25-26% in ganglion T3, while in early nymphal stages the reduction is only 8-10%. The difference in the extent of narrowing of the fibers in adult and nymphal stages is the major factor that accounts for the development of a low safety factor region for impulse propagation across T3. Analysis of the passive membrane properties of the GIN reveals that the electrotonic length of the GIN segment in T3 is identical in adult and nymphal stages. It is concluded that the functional disappearance of afferents innervating the GINs in T3 is a consequence of decreased transmission efficacy along the afferent pathways.

Afferent Pathways↗

Extracellular potassium ions mediate specific neuronal interaction.

The giant interneurons from the nerve system of the cockroach Periplaneta americana exhibit a peculiar reciprocal synaptic interaction. The synaptic potentials are not blocked by addition of 5 millimolar cobalt chloride and have an extrapolated reversal potential close to 0 millivolt. Hyperpolarizing current injected into one cell does not spread to the other. Intracellular injection of tetraethylammonium ions into one giant interneuron increases the duration of the action potential of the injected cell to 30 milliseconds and reduces the rise time and amplitude of the postsynaptic response recorded in the other giant interneuron. These results indicate that the interaction between the interneurons is not mediated by conventional chemical or electrotonic synapses.. All evidence points to generation of the potentials by localized increases in extracellular potassium concentrations as a consequence of firing of one neuron.

Action Potentials↗

Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage-dependent ionic conductances.

The electrophysiological properties of guinea-pig inferior olivary (I.O.) cells have been studied in an in vitro brain stem slice preparation. 1. Intracellular recordings from 185 neurones in this nucleus reveal that antidromic, orthodromic or direct stimulation generates action potentials consisting of a fast spike followed by an after-depolarizing potential (ADP). The ADP had an amplitude of 49 +/- 8 mV (mean +/- S.D.) and a duration which varied over a wide range with the level of depolarization. This ADP is followed by an after-hyperpolarizing potential (AHP) having an amplitude of 12 +/- 3 mV (mean +/- S.D.) from rest and lasting up to 250 msec. The AHP shows a rebound depolarization wave. 2. Synaptic activation may be obtained by peri-olivary stimulation with a bipolar electrode located in the immediate vicinity of the I.O. nucleus. These potentials are a mixture of depolarizing and hyperpolarizing synaptic events which can be reversed by direct membrane polarization. 3. Addition of tetrodotoxin (TTX) to the bath, or removal of extracellular Na, abolishes the fast initial action potential but does not modify the ADP or the AHP. Blockage of Ca conductance by Co, Mn, Cd or D600, or replacement of Ca by Mg, abolishes the ADP--AHP sequence. 4. Hyperpolarization of the neurone uncovers a low-threshold Ca conductance which is inactivated at rest and has similar pharmacological properties to the ADP. This low-threshold spike plays a central role in the rebound potential following the AHP. 5. Simultaneous impalement of I.O. neurone pairs demonstrated the presence of electrotonic coupling between neurones, which is especially prominent in the medial accessory olive.

Action Potentials↗