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M E Selzer

Publications and source records attributed to M E Selzer.

At least 55 records · Page 3Linked to original sources
PubMed1986

Determinants of directional specificity in the regeneration of lamprey spinal axons.

The projection patterns of regenerating spinal axons in the larval sea lamprey (Petromyzon marinus) were determined by intracellular injection of HRP. Four hundred and eighty-six of 562 stained axons and axon-like neurites (87%) arising from Muller and Mauthner axons, giant interneurons, and dorsal cells terminated in an orientation similar to that of their counterpart control cells. Therefore, lamprey spinal axons regenerate selectively along their normal projection paths. During the first 4 weeks of recovery, i.e., before any had regenerated beyond the transection site, 91 of 114 axons and long neurites (80%) projected in the proper direction. Thus, the correctness of the final projection patterns did not result from selective retraction of randomly directed long neurites. When the cords were doubly transected 1 cm apart, orientation of regenerating neurites remained normal both within the 1 cm island and in the adjacent spinal cord. This suggests that the directional specificity of axonal regeneration was determined neither by the location of the scar nor by the availability of channels formed by the degenerating fibers. Finally, removing 1 cm of spinal cord eliminated potential synaptic targets for regenerating axons on either side of the lesion, but did not affect the direction of axonal growth. These findings are consistent with the hypothesis that the regeneration of lamprey spinal axons is guided by local chemical cues that persist long after the pathways are formed early in development.

Animals↗
PubMed1985

Frequency-dependent effects of phenytoin on frog junctional transmission: presynaptic mechanisms.

The action of the antiepileptic drug, phenytoin, on junctional transmission at various frequencies of synaptic activation was studied in frog nerve-muscle preparation. Intracellular recordings were made from muscle end-plates, and extracellular focal and subsendothelial recordings were obtained from motor nerve terminals and their parent axons, respectively. When the motor nerve was stimulated at 100-200 Hz, exposure to the drug (0.1-0.3 mM) induced intermittent failures of junctional transmission which appeared faster as the rate of stimulation was increased. At these and at lower stimulation frequencies (30-50 Hz), in which failures of transmission occurred only rarely, phenytoin markedly limited the buildup of end-plate potential amplitude during the period of repetitive nerve stimulation (tetanic potentiation). Several lines of evidence suggest that both drug effects are consequent to a frequency-dependent depression of the action potential at motor axons and terminals, which could lead to an intermittent conduction block at the higher rates of stimulation. The selective action of phenytoin on high frequency synaptic transmission may contribute to the specificity shown by this drug in suppressing epileptic seizures while sparing neuronal activity.

Animals↗
PubMed1985

Regeneration of functional synapses between individual recognizable neurons in the lamprey spinal cord.

In 4- to 5-year-old sea lamprey larvae that had recovered from complete transection of the spinal cord, pairs of giant interneurons on opposite sides of the scar were impaled with microelectrodes. In 4 of 30 pairs, stimulation of the caudal cell elicited a monosynaptic electrochemical excitatory postsynaptic potential in the rostral cell. Fifty percent of such pairs were synaptically linked in control lampreys without transections. These results show regeneration of functional synaptic connections between individual neurons in a vertebrate central nervous system.

Animals↗
PubMed1985

Suppression by phenytoin of convulsant-induced afterdischarges at presynaptic nerve terminals.

The mechanisms underlying the induction of afterdischarges at presynaptic nerve terminals by convulsant aminopyridines and their suppression by the anticonvulsant drug phenytoin were studied at the frog neuromuscular preparation. Addition of aminopyridine to the perfusing solution induced the appearance of afterdischarges in motor nerve fibres following their primary response to a single nerve stimulus. The afterdischarges seemed to originate at or near the nerve terminals and to propagate both antidromically and orthodromically. The latter resulted in repetitive activation of the neuromuscular synapse. Focal recordings of nerve terminal potentials suggested that aminopyridines may induce afterdischarges by slowing spike repolarization and thereby producing a prolonged depolarization of nerve terminals. Phenytoin suppressed the aminopyridine-induced afterdischarges and the resultant repetitive excitation of the postsynaptic muscle fibres. This effect of phenytoin was associated with a depression of the action potential at the motor nerve terminals but not at their parent axons. These results single the presynaptic nerve terminals as preferential sites for convulsant and anticonvulsant actions.

4-Aminopyridine↗
PubMed1985

Thyrotropin-releasing hormone in lamprey central nervous system.

Thyrotropin-releasing hormone (TRH) levels were measured by radioimmunoassay in the CNS of larval and adult sea lampreys and adult river lampreys. In larval sea lampreys, the pituitary complex contained approx. 609 pg TRH/mg, brain contained 43.5 +/- 5.5 pg/mg (mean +/- S.E.M.) while the spinal cord contained 11.2 +/- 2.3 pg/mg. Corresponding levels in the adult sea and river lampreys were similar. Complete spinal transection did not significantly alter TRH levels below the lesion. Thus, the spinal cord contains TRH independent of supraspinal axonal projections.

Animals↗
PubMed1985

On the mechanism by which phenytoin blocks post-tetanic potentiation at the frog neuromuscular junction.

Post-tetanic potentiation (PTP) was elicited at the frog sartorius and cutaneous pectoris neuromuscular junctions. A 30-sec, 30-Hz tetanus produced a 2- to 3-fold post-tetanic increase in endplate potential (EPP). In surface-recorded responses this PTP decayed in a double exponential way with time constants of 12.7 sec +/- 2.4 (SEM) and 146.8 sec +/- 36.6. In acute experiments 0.2 to 0.8 mM phenytoin (5,5-diphenylhydantoin, DPH) dramatically and reversibly reduced the early component. The late component was also reduced, although to a lesser extent and often not reversibly. DPH reduced PTP even when there was no failure of the EPP during the tetanus. Thus, the DPH effect did not require a complete block of the presynaptic action potential. At longer exposures and higher DPH concentrations EPP failures did develop, and this was associated with a more profound suppression of PTP. PTP was also elicited in tetrodotoxin (TTX)-containing solutions using electronic stimulation of nerve terminals to elicit transmitter release. This PTP had a much shorter duration (about 30 sec) than that seen in normal Ringer's solution and was followed by depression of EPP amplitudes. Thus, sodium entry into nerve terminals enables a mechanism which greatly prolongs PTP. DPH had no effect on PTP in TTX. These results, together with others in the literature, suggest that the reduction of PTP by DPH involves a graded reduction of sodium influx into nerve terminals during high rates of axon stimulation. The development of all-or-none failures of the presynaptic action potential results in even greater suppression of PTP.

Action Potentials↗
PubMed1984

Phenytoin reduces frequency potentiation of synaptic potentials at the frog neuromuscular junction.

The action of the commonly used antiepileptic drug phenytoin on frequency potentials was studied at the frog neuromuscular junction. Whereas the drug, at concentrations of 0.1-0.3 mM, had only a slight effect on EPPs evoked by nerve stimulation at a frequency of 0.5 Hz, it strongly suppressed their potentiation during tetanic nerve stimulation at 30 Hz. The post-tetanic potentiation of the EPPs was also reduced by the drug. These effects occurred without a blockade of invasion of the nerve impulse into the presynaptic terminal during the tetanus, and thus indicate a specific frequency-dependent depressant action of the drug on neurally-evoked transmitter release.

Animals↗
PubMed1984

Directional specificity in the regeneration of lamprey spinal axons.

After spinal transection in ammocoetes (lamprey larvae) 4 to 5 years old, functional recovery is accompanied by a limited regeneration in which axons grow as far as 5 millimeters beyond the scar. In axotomized giant interneurons labeled intracellularly with horseradish peroxidase 16 to 120 days after transection, 74 percent of regenerating neurites grew in their normal projection pattern, rostal and contralateral to the cell body. One third of the neurites originated anomalously from posterior dendrites. Despite their initial abnormal orientation, 80 percent of these neurites looped contralaterally and rostrally to assume the normal projection path. The directional specificity persisted when giant interneurons were located in islands formed by double simultaneous cord transection. This limited regeneration seems to be characterized by directional selectivity that cannot be attributed to nonspecific influences, such as a tendency of neurites to grow in an already established direction or a trophic effect of the zone of injury.

Animals↗
PubMed1984

Glycine uptake by lamprey spinal neurons demonstrated by light microscopic autoradiography.

We have mapped the neuronal uptake of 3H-glycine in the spinal cords of large larval sea lampreys: Petromyzon marinus. Spinal cords were incubated in 10(-6) M 3H-glycine for 15 minutes. They were rinsed in lamprey solution, fixed in phosphate-buffered 2% glutaraldehyde, and washed in phosphate buffer. They were then sectioned with a cryostat at 16-m thickness or dehydrated, embedded in Epon, and sectioned at 1-4 micron. Sections were coated with a photographic emulsion and maintained at 4 degrees C for 1-7 days. By sectioning horizontally, it was possible to obtain complete serial reconstructions of up to 1.5-mm lengths of cord in 100-150 sections. The outlines of labelled cells were traced with a Nikon drawing attachment. For one Epon-embedded spinal cord sectioned at 4 micron, tracings were superimposed to form complete maps for 0.6-1.5-mm lengths in three representative regions of cord: rostral (gill region), caudal (dorsal fin region), and midsection. The labelled neurons were small (5-10-micron diameter) cells distributed throughout the central gray columns. They numbered 22 cells per hemisegment in the rostral region, 33 in the midsection, and 43 in the caudal region. None of the previously identified cell types were labelled, including lateral interneurons, edge cells, giant interneurons, dorsal cells, and Müller and Mauthner axons.

Animals↗
PubMed1984

Electrophysiologic evidence of regeneration of lamprey spinal neurons.

Morphologic evidence has shown that the anteriorly projecting axons of giant interneurons (GIs) can regenerate after spinal transection in larval sea lampreys (19). In the present study, we showed that the regenerating neurites of GIs were electrically excitable. We also showed evidence for regeneration of descending afferent connections to GIs. Spinal cords were transected at the level of the cloaca. After at least 70 days recovery, GIs located 1.5 to 17.0 mm below the scar were impaled with microelectrodes. Stimulating electrodes were placed at various distances above the scar. Six of 13 GIs located 4 to 17 mm below the scar could be activated antidromically. For 1 GI, the rostralmost point of stimulation which elicited these responses was 13.5 mm above the scar. For the others, the range was 0.5 to 4.5 mm. Estimated average conduction velocity in regenerated neurites was 0.50 m/s compared with 1.94 m/s for the parent axon. Twelve GIs could be orthodromically activated by fixed-latency EPSPs. The most rostral point of stimulation that could elicit such responses was 0.5 to 8.5 mm above the scar. There was an inverse relationship between the farthest distance of stimulation and the distance of the GI from the scar. These findings are consistent with the hypothesis that regeneration of axons across a spinal transection is limited to neurons whose cell bodies are situated within 1 to 2 cm from the transection, and that regenerating neurites grow only a few millimeters beyond the scar.

Afferent Pathways↗
PubMed1983

Axonal regeneration in lamprey spinal cord.

Spinal cords of sea lamprey larvae were transected at one of two levels: (a) rostral, at the last gill, or (b) caudal, at the cloaca. Following various recovery times, regeneration of the posteriorly projecting giant reticulospinal axons (RAs) was demonstrated by intra-axonal injection of horseradish peroxidase (HRP). Regeneration of axons of anteriorly projecting dorsal cells (DCs) and giant interneurons (GIs) was demonstrated by intrasomatic HRP injection into cells located just below the transection scar. After 40 days of recovery, 55% of proximally transected RAs (rostral cut) regenerated at least as far as the center of the scar, whereas only 15% of distally transected RAs (caudal cut) did so. Maximum distance of regeneration was 5.3 mm beyond the scar for proximally transected RAs but only 38 u for distally transected RAs. Proximally transected RAs also branched more profusely than distally transected ones. These data (when combined with others in the literature) suggest that the regenerative capacity of RAs may decrease with distance of axotomy from the cell body. Distance of regeneration and degree of branching of proximally transected RAs peaked between 40 and 100 days. Thereafter, there appeared to be a tendency toward neurite retraction. Of axotomized GIs, 76% regenerated anteriorly at least as far as the center of a caudal transection scar (GIs are located only in the caudal part of the cord). The maximum distance of regeneration was 1.3 mm beyond the scar. Of DC axons, 56% regenerated anteriorly at least as far as the transection site. The maximum distance was 1.1 mm beyond the scar. DCs located just below a caudal transection regenerated at least as well as those located below a rostral transection. Axonal regeneration was also demonstrated for a few lateral cells, edge cells, and crossed caudally projecting interneurons.

Animals↗
PubMed1981

Autoradiographic studies of estrogen target cells in the forebrain of larval lamprey, Petromyzon marinus.

The distribution of estrogen target neurons is assessed in the forebrain of larval sea lamprey, Petromyzon marinus, by the use of thaw-mount autoradiography. Following the injection of [3H]estradiol-17 beta, radioactively labeled neurons are found in the ventral telencephalon and in the ventral and dorsal diencephalon, including preoptic, central hypothalamic, and thalamic regions. In the pallium no labeled cells exist. Pituitary glands, obtained from two of the animals, contain no labeled cells. The topographical distribution of estrogen target neurons in larval lamprey is similar to that of adult animals. The number of target neurons in larval lamprey, however, is lower than in the adult. The presence of target cells indicates that gonadal steroids act on the brain at this early stage of development. The lack of concentration of estrogen in pituitary cells suggests an absence of feedback regulation of estrogen at the pituitary level.

Animals↗
PubMed1981

The inulin space of the lamprey spinal cord.

The distribution of [14C]inulin was measured in isolated spinal cords of larval and feeding stage adult forms of sea lamprey (Petromyzon marinus) and expressed in per cent of total cord wet weight. In larval cord the apparent inulin space reached a plateau value of 32--33% within 2.5. min. This correlates well with electrophysiological experiments in which 10(-7) M tetrodotoxin added to the perfusion fluid blocked the responses of giant interneurons to both intracellular and rostral cord stimulation in 1 to 2 min. Thus the plateau level of inulin space probably represents the extracellular space. [14C]Mannitol did not reach a steady distribution space even after 30 min of incubation. Therefore, mannitol is not an accurate extracellular space indicator in the isolated lamprey spinal cord. The inulin space increased with increasing temperature of incubation. Average inulin spaces for larval spinal cords incubated at 5, 10 and 22 degrees C were approximately 26%, 33% and 42% respectively. The inulin space of isolated adult lamprey spinal cords was about 18--19%. Since in larvae the inulin space did not vary consistently with the sizes (and therefore presumably the ages) of the animals, it is likely that the reduction in inulin space during maturation does not occur gradually during the larval phase, but probably occurs during transformation. The difference between the inulin spaces of isolated larval and adult spinal cords is reflected qualitatively in the electron microscopic appearance of the extracellular space. We conclude that the inulin space in the lamprey spinal cord behaves similarly to the picture of the mammalian brain extracellular space which has emerged in recent years. Because of the rapidity of inulin diffusion in the lamprey cord and the unambiguous time-dependent behavior of the inulin space of the isolated lamprey cord, the latter would seem to be useful model for the extracellular space of the vertebrate central nervous system.

Aging↗
PubMed1981

Glutamic acid decarboxylase in sea lamprey (Petromyzon marinus): characterization, localization, and developmental changes.

We have carried out assays for glutamic acid decarboxylase (GAD) in homogenates of brain and spinal cord from larval and adult sea lamprey (Petromyzon marinus). The enzyme had similar characteristics in both stages. Optimal pH was 6.8; optimal temperature was 27-30 degrees C; Km at 27 degrees C was 5 mM. GAD activity was distributed uniformly along the length of the spinal cord. Specific activities for the larval cord and brain were 26 and 63 nm CO2/mg protein/h, respectively. The specific activities for the adult cord and brain were 29 and 236 nm CO2/mg protein/h, respectively. Thus, the activity of cord homogenates did not change significantly between larval and adult stages, but that of the brain increased about fourfold.

Aging↗
PubMed1980

Estrogen target cells in the forebrain of river lamprey, Ichthyomyzon unicuspis.

Estrogen-concentrating cells in the brain of river lamprey, Ichthyomyzon unicuspis, are identified and mapped by thaw-mount autoradiography. After injection of 3H-estradiol-17 beta, cells with nuclear concentration of radioactivity are found in the ventral periventricular area of the telencephalon, and in preoptic, central hypothalamic, and thalamic regions of the diencephalon, while in the pallium no such target cells are found. Injection of unlabeled estradiol prior to the administration of 3H-estradiol reduces of eliminates the nuclear concentration of radioactivity. The autoradiographic results demonstrate the presence of estrogen target cells in the brain of descendents of one of the phylogenetically earliest vertebrate lines. The topographical distribution of these target neurons, which are accumulated in certain periventricular structures, is similar to the distribution of estrogen target neurons described previously for other nonmammalian and mammalian vertebrates. Accordingly, estrogen feedback and activation sites are present throughout vertebrate phylogeny.

Animals↗
PubMed1979

Projections of lamprey spinal neurons determined by the retrograde axonal transport of horseradish peroxidase.

The spinal cords of larval sea lampreys (Petromyzon marinus) and adult river lampreys (Ichthyomyzon unicuspis) were injected with horseradish peroxidase through a transection 1 cm caudal to the last gill. Some animals also had a spinal hemisection 1 cm caudal to the injection. After recovery periods of 1 to 52 days, the spinal cords were treated with diaminobenzidene and hydrogen peroxide, and the projections of various cell types determined in wholemount slides. From these observations the following conclusions were drawn. Most dorsal cells (primary sensory cells) are bipolar with a long rostral projection and a short caudal projection of no more than 5-10 mm. Both processes travel in the ipsilateral dorsal column. Their peripheral processes enter the dorsal roots as branches of their central axons. Some dorsal cells send processes out three or more dorsal roots both rostral and caudal to the cell body. Myotomal motoneurons have characteristic locations in the medial gray column and send prominent transversely oriented dendrites into the lateral columns. A few motoneurons are unusually large. In addition to giant interneurons the majority of smaller rostrally projecting interneurons also have decussating axons. A recently described cell type, the oblique bipolar cell, appears to have an exclusively crossed rostral projection. Although most edge cells project rostrally, as many as 20% may have a caudal projection or both rostral and caudal projections. Edge cells project equally to the ipsilateral and contralateral spinal hemicord, but their processes do not extend more than about 18 mm in sea lamprey larvae and 37 mm in adult river lampreys. Lateral cells project exclusively to the ipsilateral caudal hemicord. A few cells which resemble lateral cells in location and in possessing large lateral dendrites, project rostrally. However, these have atypical morphologic features which probably distinguish them from true lateral cells. Thus far, regardless of cell type, all decussating axons seem to pass ventral to the central canal, while decussating medial dendrites pass dorsally.

Animals↗
PubMed1979

The effect of phenytoin on the action potential of a vertebrate spinal neuron.

The effect of phenytoin (PTN) 20 microgram/ml was tested on the passive membrane properties and the action potential of the dorsal cells in the spinal cord of the river lamprey. Dorsal cells are primary sensory neurons with no synaptic input, and thus allow examination of membrane properties in the absence of contaminating synaptic currents. PTN did not affect the resting membrane potential and slightly raised the input resistance. However, it greatly raised the threshold voltage and current for activation of action potentials by intracellularly injected current. It also reduced the maximum rate of rise of the action potential, the spike overshoot and the spike undershoot, while increasing the spike duration. In contrast to findings in other vertebrate sensory neurons, dorsal cell action potentials were blocked in zero sodium or tetrodotoxin, and not affected by zero calcium or 1 mM manganese. Thus they PTN on dorsal cells is that it partially blocks the activated sodium conductance increase of the action potential. Because a long delay was observed for maximal effect of PTN and for washout, it is postulated that the drug may require partitioning into the lipid membrane, or entry into the cell for its pharmacological action.

Action Potentials↗