Wiley
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A specific 70K protein found in epileptic rat cortex: Induction of bursting activity and negative resistance by its intracellular application in <i>Euhadra</i> neurons Abstract The effect of 70‐kD protein (P70, a specific protein found in cobalt‐induced epileptogenic focus of rat cerebral cortex) on membrane properties was examined in identified neurons of the snail, Euhadra peliomphala , using the pressure injection method combined with the voltage‐clamp technique. In neurons that normally exhibited spontaneous regular firing, intracellular injection of P70 elicited bursting activity and a negative slope resistance (NSR) region in their current‐voltage (I‐V) curve in a manner corresponding to the duration of its injection. These responses were suppressed by prior injection of an antibody to P70 into the neurons, and were markedly inhibited by a reduction of extracellular Na+ ions and the anticonvulsant agent phenytoin, but not by Co2+ ‐substituted Ca2+ ‐free saline. In addition, intracellularly applied P70 potentiated both bursting activity and the NSR induced by a Na channel activator, veratridine. However, prior application of a saturating dose of this activator occluded the effect of P70. These results suggest that P70 elicits a Na+ ‐dependent negative resistance, which may contribute to the generation of bursting activity.
Wiley - Tập 22 Số 3 - Trang 287-297 - 1991
Fos: An immediate‐early transcription factor in neurons Abstract In the past several years a great deal of evidence has accumulated linking neuronal activation events to the regulation of gene expression. We have pursued an analysis of c‐fos regulation in the nervous system to elucidate the molecular mechanisms involved in stimulus‐transcription coupling. The c‐fos gene can be viewed as an archetype of the set of cellular immediate‐early genes encoding transcription factors. These genes are believed to function in coupling short‐term signals elicited by extracellular to long‐term changes in cellular phenotype by orchestrating alterations in target gene expression. Several animal seizure models have been used to demonstrate the activation of gene expression in specific populations of neurons. Using a transgenic mouse approach, based on a foslacZ fusion gene, we now demonstrate an association between c‐fos expression and cell death in the nervous system. A delayed and protracted induction was observed following surgical lesion and in response to neurotoxin exposure. This system allows us to determine, for the first time, the DNA regulatory sequences that are responsible for the induction of gene expression in neurons in vivo . Furthermore, foslacZ transgenic mice provide a unique resource for identifying cell populations that respond to specific stimuli or that are susceptible to particular toxins. © 1995 John Wiley & Sons, Inc.
Wiley - Tập 26 Số 3 - Trang 403-412 - 1995
A developmental analysis of spontaneous and reflexive reversals in the nematode <i>Caenorhabditis elegans</i> Abstract Reversals of forward locomotion in the nematode Caenorhabditis elegans are thought to be mediated by a common neural circuit, the touch withdrawal circuit. Despite substantial neuroanatomical changes over postembryonic development, one reversal behavior, the head‐touch withdrawal reflex, does not appear to change over development (Chalfie and Sulston, 1981). The experiments reported here indicate that two other reversal behaviors, spontaneous reversals and the tap reversal reflex to vibratory stimuli, show developmental changes. Young adult animals showed higher frequencies of spontaneous reversals than all other developmental stages, while larval stages differed from adults in their pattern of responses to tap. Although animals of all stages reversed in response to touch, taps elicited both reversals and accelerations of forward movement. In response to single taps, larval stages reversed on approximately half the occasions; young adult and 4‐day‐old adults almost always reversed. Increasing stimulus magnitudes increased the probability of accelerations at all developmental stages, but larval stages showed fewer reversals and more accelerations than adults. The behavioral changes observed coincide with known periods of neuroanatomical change in the touch withdrawal circuit. The addition of a late‐developing sensory neuron, AVM, is implicated in the behavioral differences between juveniles and adults.
Wiley - Tập 21 Số 4 - Trang 543-554 - 1990
Synaptic <i>drosophila</i> UNC‐13 is regulated by antagonistic G‐protein pathways via a proteasome‐dependent degradation mechanism Abstract UNC‐13 is a highly conserved plasma membrane‐associated synaptic protein implicated in the regulation of neurotransmitter release through the direct modulation of the SNARE exocytosis complex. Previously, we characterized the Drosophila homologue (DUNC‐13) and showed it to be essential for neurotransmitter release immediately upstream of vesicular fusion (“priming”) at the neuromuscular junction (NMJ). Here, we show that the abundance of DUNC‐13 in NMJ synaptic boutons is regulated downstream of GαS and Gαq pathways, which have inhibitory and facilitatory roles, respectively. Both cAMP modulation and PKA function are required for DUNC‐13 synaptic up‐regulation, suggesting that the cAMP pathway enhances synaptic efficacy via DUNC‐13. Similarly, PLC function and DAG modulation also regulate the synaptic levels of DUNC‐13, through a mechanism that appears independent of PKC. Our results suggest that proteasome‐mediated protein degradation is the primary mechanism regulating DUNC‐13 levels at the synapse. Both PLC‐ and PKA‐mediated pathways appear to regulate synaptic levels of DUNC‐13 through controlling the rate of proteasome‐dependent DUNC‐13 degradation. We conclude that the functional abundance of DUNC‐13 at the synapse, a key determinant of synaptic vesicle priming and neurotransmitter release probability, is primarily regulated by the rate of protein degradation, rather than translocation or transport, convergently controlled via both cAMP and DAG signal transduction pathways. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 417–438, 2003
Wiley - Tập 54 Số 3 - Trang 417-438 - 2003
Multiple forms of acetylcholinesterase and their distribution in endplate and non‐endplate regions of rat diaphragm muscle Abstract The properties of the cholinesterase activity in homogenates of whole rat diaphragm and of innervated (+EP) and non‐innervated (−EP) regions of the muscle have been investigated. Under standard assay conditions, over 90% of the cholinesterase activity of whole muscle homogenates was due to specific acetylcholinesterases. The specific activity of acetylcholinesterase was higher in +EP regions of muscle than in −EP regions. About 40% of the total activity was calculated to be specifically associated with the endplates. When a high speed supernatant fraction of muscles homogenized in 1 M NaCl, 0.5% Triton X‐100 was subjected to velocity sedimentation in a sucrose gradient, and three species of acetylcholinesterase activity with sedimentation constants of 4 S, 10 S and 16 S were observed. All three forms were stable under the conditions of sedimentation and had buoyant densities of approximately 1.28. All three hydrolyzed β‐methylacetylcholine at approximately 30% the rate that acetylcholine was hydrolyzed. The 10 S and 16 S forms were inhibited by concentrations of acetylcholine over 1.25 mM, but no substrate inhibition was observed with the 4 S enzyme. Velocity sedimentation of extracts from +EP and −EP regions of muscle demonstrated that the 4 S and 10 S forms of the enzyme were distributed throughout the muscle while the 16 S form was found only in +EP regions. Extracts of the phrenic nerve contained only 4 S and 10 S forms. Thus, the 16 S form of acetylcholinesterase is specifically associated with endplate regions of muscle and may correspond to the endplate enzyme. Seven days after denervation of the diaphragm, both endplate‐specific cholinesterase activity and the cholinesterase activity in −EP regions of muscle were decreased. Although the activity of all three forms of acetylcholinesterase were decreased in denervated muscle, the largest proportional decrease occurred in the activity of the 16 S form.
Wiley - Tập 4 Số 4 - Trang 343-361 - 1973
Neurotrophic control of 16S acetylcholinesterase at the vertebrate neuromuscular junction Abstract Endplate 16S acetylcholinesterase (16S‐AChE) from rat anterior gracilis muscle was assessed, 6 hr to 10 days after denervation, by velocity sedimentation analysis on linear sucrose gradients. The innervating obturator nerve was transected either close (1‐2 mm, short stump) or far (35‐40 mm, long stump) from the muscle. In both instances, the activity of 16S‐AChE gradually decreased and reached approximately the same level (10%‐20% of control) by 6 days after denervation. However, enzymatic decay started considerably earlier in short stump (12‐24 hr) as compared to long stump (4‐5 days) preparations, i.e., the time of onset of 16S‐AChE loss depended on the length of nerve that remained attached to the muscle. Whether this result extended to other AChE molecular forms (10S, 4S) in muscle endplates could not be determined because, in contrast to 16S‐AChE, these forms were also detected in red blood cells (4S) and plasma (10S). Only small amounts of 16S‐AChE were found in intact obturator nerves (1/100 of that in gracilis endplate regions). Thus a faster depletion of enzyme from shorter nerve stumps after axotomy could not entirely account for the substantial effect of nerve stump length on 16S‐AChE. Since muscle contraction ceases immediately following nerve transection, regardless of nerve stump length, the results can be ascribed to the lack of some neural influence other than nerve‐evoked muscle activity. The present findings are consistent with the view that maintenance of 16S‐AChE at neuromuscular junctions primarily depends on regulatory substances which are conveyed by axonal transport and released from nerve terminals.
Wiley - Tập 10 Số 5 - Trang 441-454 - 1979
Neurotrophic control of 16S acetylcholinesterase from mammalian skeletal muscle in organ culture Abstract The effects of rat obturator nerve extracts on total and 16S acetylcholinesterase (AChE) activity were studied in endplate regions of denervated anterior gracilis muscles maintained in organ culture for 48 hr. The decrease of total AChE activity in cultured muscles was similar to that observed in denervated muscles in vivo . This decrease in activity was partly prevented by addition of either 100 or 200 μl nerve extract (2.7 mg/ml protein) to the nutrient medium. Nerve extract treatment also decreased the release of AChE activity from the muscle into the bathing medium. Conversely, rat serum (20 μl; 90 mg/ml protein) had no effect on total AChE activity in muscle endplates, nor on release of the enzyme by the muscle. The 16S form of AChE was confined to motor endplate muscle regions and its activity was drastically decreased by denervation in both organ culture and in vivo preparations in a comparable manner. Nerve‐extract supplemented cultures contained a significantly (p ≪ 0.001) larger amount of endplate 16S AChE activity (140–145%) than the corresponding controls (100‐). Our results suggest that some nerve soluble substance, other than serum contaminants or 16S AChE itself, affects the maintenance of 16S AChE at the neuromuscular junction.
Wiley - Tập 11 Số 6 - Trang 557-570 - 1980
Activity patterns of catecholamine‐containing pontine neurons in the dorso‐lateral tegmentum of unrestrained cats Abstract Single catecholamine‐containing neurons in the dorso‐lateral pontine tegmentum were recorded in unanesthetized, freely behaving cats. Microscopic lesions were made on each recorded unit and subsequently identified for catecholamines by fluorescence histochemical analysis. The majority of the NE‐containing neurons exhibited low spontaneous discharge rates in quiet wakefulness and in slow wave sleep. In paradoxical sleep, the medially located NE‐containing neurons tend to exhibit ursting discharges which are closely related to individual PGO waves. The laterally or dorsally situated NE units fire more slowly and tend to derease their firing activity during paradoxical sleep. Tonically active, relatively fast NE‐containing units were also found. Often, those neurons showed greatly increased activity before the cat awoke from either slow wave sleep or paradoxical sleep, with activity persisting during the early moments of waking. The combination of histochemical and electrophysiologic methods proved essential for correlating neurochemistry and function within the heterogeneous NE‐containing nuclei of the cat pons.
Wiley - Tập 5 Số 6 - Trang 527-544 - 1974
Parallel processing of short‐term memory for sensitization in <i>Aplysia</i> Abstract How is the short‐term memory for a single form of learing distributed among the various elements of a neuronal circuit? To answer this question, we examined the short‐term memory for sensitization, using the siphon component of the defensive gill‐ and siphon‐withdrawal reflex. We found that the memory for short‐term sensitization is represented by at least four sites of circuit modification, each involving a different type of plasticity. These include (1) presynaptic facilitation of the sensory neuron connections onto both interneurons and motorneurons; (2) presynaptic inhibition at the connections of the L30 inhibitory neurons onto the excitatory interneuron L29; (3) posttetanic potentiation of the excitatory connections made by L29 onto a specific subclass of siphon motorneurons, the LFS cells; and (4) an increase in the tonic firing rate of the LFS siphon motor neurons, resulting in neuromuscular facilitation. Each of the heterosynaptic changes seems to involve a common modulatory transmitter and to utilize a common second messenger system. Moreover, each of these sites seems capable of encoding a different component of the short‐term memory. Facilitation of the connections of sensory neurons should contribute to the increase in amplitude of the response; the disinhibition of the L29 interneurons and the posttetanic potentiation at L29 synapses should contribute to an increase in the duration of the response; and the increase in tonic firing of the LFS subclass of siphon motor neurons seems capable of contributing both to an increase in response amplitude and to changes in response topography.
Wiley - Tập 19 Số 4 - Trang 297-334 - 1988
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