Studies of consciousness are hindered by the complexity of the brain, but it is possible to study... more Studies of consciousness are hindered by the complexity of the brain, but it is possible to study the consciousness of a sensation, namely pain. Three systems are necessary to experience pain: the somatosensory system conveys information about an injury to the thalamus where an awareness of the injury but not the painfulness emerges. The thalamus distributes the information to the affective system, which modulates the intensity of the pain, and to the cognitive system that imparts attention to the pain. Imaging of patients in pain and those experiencing placebo and hypnosis-induced analgesia shows that two essential cortical circuits for pain and attention are located within the anterior cingulate cortex. The circuits are activated when a high-frequency input results in the development of a long-term potentiation (LTP) at synapses on the apical dendrites of pyramidal neurons. The LTP acts via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA)...
... RICHARD T. AMBRON$ AND RONALD A. PIERINGER~ From the Department of Biochemistry, Temple Unive... more ... RICHARD T. AMBRON$ AND RONALD A. PIERINGER~ From the Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 191&O ... Studies on the in viva incorporation of 3'Pi into S. jaecalis lipids were carried out by using 3% trypticase ...
Nerve injury, tissue damage, and inflammation all cause hyperalgesia. A factor contributing to th... more Nerve injury, tissue damage, and inflammation all cause hyperalgesia. A factor contributing to this increased sensitivity is a long-term (>24 hr) hyperexcitability (LTH) in the sensory neurons that mediate the responses. Using the cluster of nociceptive sensory neurons inAplysia californicaas a model, we are examining how inflammation induces LTH. A general inflammatory response was induced by inserting a gauze pad into the animal. Within 4 days, the gauze is enmeshed in an amorphous material that contains hemocytes, which comprise a cellular immune system. Concurrently, LTH appears in both ipsilateral and contralateral sensory neurons. The LTH is manifest as increased action potential discharge to a normalized stimulus. Immunocytochemistry revealed that hemocytes have antigens recognized by antibodies to TGFβ1, IL-6, and 5HT. When a localized inflammation was elicited on a nerve, hemocytes containing the TGFβ1 antigen were present near axons within the nerve and those containing...
... ing the cells on a DeLaval continuous flow centrifuge, the lipids were extracted from the cel... more ... ing the cells on a DeLaval continuous flow centrifuge, the lipids were extracted from the cells with chloroform-methanol (1 :I, v/v), and were partially purified on a column of silicic acid by the technique of Vorbeck and Xlarinetti (X), which has been confirmed by Rouser et al. ...
It was found previously that transection of one branch of the bifurcate axon of a giant serotoner... more It was found previously that transection of one branch of the bifurcate axon of a giant serotonergic neuron of Aplysia causes a proportionate decrease in the export of transmitter storage vesicles from the cell body, despite the ability of the remaining branch to transport all of the vesicles normally exported (Aletta and Goldberg, 1982). We report here evidence that this down-regulation is achieved by a decrease in the production of vesicles, rather than a slowing of the processing of vesicles for export from the cell body. Counts of serotonergic vesicles in the cell body show that the size of the somal pool of vesicles is not increased at a time when their rate of export has been halved. Also, transection of one or both branches of the axon decreases the amount of 3H-fucose incorporated during a short period into a putative vesicle membrane glycoprotein but not into other glycoproteins. The results indicate that axotomy should be a useful technique for studying the mechanism of re...
The cell body of R2, a giant cholinergic neuron of Aplysia californica, resides in the abdominal ... more The cell body of R2, a giant cholinergic neuron of Aplysia californica, resides in the abdominal ganglion, whereas its synapses are on thousands of unicellular mucus glands located in the skin. Due to the great spatial separation between the site of macromolecular synthesis and the presynaptic terminals, rapid axonal transport can be used to segregate synaptic proteins from those to be used elsewhere in the cell. The proteins of R2 were labeled by incubating the abdominal ganglion in [35S]methionine for 5 hr in a chamber separated from the rest of the isolated central nervous system. After 50 hr, 28 radiolabeled proteins were reproducibly found by one- and two- dimensional polyacrylamide gel electrophoresis to be transported to the distal regions of peripheral nerves P6, P7, and P8 that innervate the parapodia and middle body wall. We are sure that R2 is the source of these proteins since radioautography of sections taken throughout the nervous system, complemented by cobalt tracing...
The neuron is a highly differentiated cell consisting of distinct regions—cell body, axon, termin... more The neuron is a highly differentiated cell consisting of distinct regions—cell body, axon, terminal—that differ in structure and function. It is likely that characteristic differences in macromolecular composition underlie regional differentiation. Because synthesis of macromolecules occurs primarily, if not exclusively, in the cell body, there are constraints on how regional biochemical differences might be established. We can think of three mechanisms: (1) differential export of macromolecules from the cell body and subsequent selective axonal transport to terminals; (2) selective import from enveloping glial cells; and (3) specific modifications of macromolecules in the axon or at terminals. There is much evidence to support the first mechanism (Ambron et al., 1974a; Dahlstrom, 1971; Ochs, 1972). As for the second, transfer of materials between glial cells and neurons has frequently been postulated (Singer, 1968), but only recently was it convincingly demonstrated (Lasek et al., 1977). Finally, there is some evidence for modification of macromolecules by glycosylation at synapses in mouse brain (Dutton et al., 1973) and in Aplysia axons (Ambron and Treistman, 1977) (also see below).
Over the last two decades, the autogenous venous nerve conduit (AVNC) has been established as an ... more Over the last two decades, the autogenous venous nerve conduit (AVNC) has been established as an effective treatment modality for the repair of nerve gaps less than 3 cm. In this study, the spatial-temporal progression of Schwann-cell migration and peripheral-nerve regeneration across a 10-mm gap bridged by a venous conduit was examined, using immunoctyochemical techniques. Histologic analysis revealed that the process of nerve regeneration through an AVNC occurs in four phases: the hematoma phase, cellular migration phase, axonal advancement phase, and myelination and maturation phase. The authors found that: 1) the lumen of the vein conduit remains patent throughout the process of nerve regeneration; 2) Schwann cells migrate into the vital space of the vessel lumen from the proximal and distal nerve stumps; 3) axonal growth into the conduit lags behind Schwann-cell migration; 4) Schwann cells migrate to the regenerating axons to form mature nodes of Ranvier when the distal stump is present; and 5) mechanical injury alone is sufficient to induce axonal outgrowth from the proximal nerve stump.
The original article to which this Erratum refers was published inJournal of Neurobiology (2003) ... more The original article to which this Erratum refers was published inJournal of Neurobiology (2003) 57(2) 204–220The name of the third author of this article was spelled incorrectly. It should read:Ying‐Ju SungThe publisher regrets this error.
Injury to a peripheral nerve initiates changes that can lead to regeneration of the damaged axons... more Injury to a peripheral nerve initiates changes that can lead to regeneration of the damaged axons. How information about a distant injury is communicated to the cell body is not clear. Using the nervous system of Aplysia californica, we tested the idea that some of this information is conveyed via positive injury signals-axoplasmic proteins that are activated at the injury site and transported to the cell soma. We collected these proteins by crushing pedal nerves and then placing a ligation proximal to the ligation. The contralateral nerves were ligated as controls. Twenty h later, axoplasm was extruded from the nerve segment just distal to the ligation on the crushed nerves (cr/lig) and on the control nerves (lig). The total proteins were rhodaminated and injected into the cytoplasm of neurons in vitro to look for nuclear import. Punctate fluorescence was detected in the nucleus of all seven neurons injected with the cr/lig axoplasm. Only two of five neurons injected with lig axoplasm had any fluorescence. Equal amounts of cr/lig and lig axoplasm were then injected directly into the cell bodies of neurons maintained in vitro. The cells injected with cr/lig axoplasm exhibited renewed growth and significantly longer survival: 25.9 +/- 2.1 days (mean +/- SEM: n = 22) relative to the cells injected with lig axoplasm (15.3 +/- 1.2 days; n = 14) and to those that were not injected (12.2 +/- 1.7 days; n = 24). Fractionation of the cr/lig axoplasm indicated that different factors are responsible for growth and survival.
Studies of consciousness are hindered by the complexity of the brain, but it is possible to study... more Studies of consciousness are hindered by the complexity of the brain, but it is possible to study the consciousness of a sensation, namely pain. Three systems are necessary to experience pain: the somatosensory system conveys information about an injury to the thalamus where an awareness of the injury but not the painfulness emerges. The thalamus distributes the information to the affective system, which modulates the intensity of the pain, and to the cognitive system that imparts attention to the pain. Imaging of patients in pain and those experiencing placebo and hypnosis-induced analgesia shows that two essential cortical circuits for pain and attention are located within the anterior cingulate cortex. The circuits are activated when a high-frequency input results in the development of a long-term potentiation (LTP) at synapses on the apical dendrites of pyramidal neurons. The LTP acts via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA)...
... RICHARD T. AMBRON$ AND RONALD A. PIERINGER~ From the Department of Biochemistry, Temple Unive... more ... RICHARD T. AMBRON$ AND RONALD A. PIERINGER~ From the Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 191&O ... Studies on the in viva incorporation of 3'Pi into S. jaecalis lipids were carried out by using 3% trypticase ...
Nerve injury, tissue damage, and inflammation all cause hyperalgesia. A factor contributing to th... more Nerve injury, tissue damage, and inflammation all cause hyperalgesia. A factor contributing to this increased sensitivity is a long-term (>24 hr) hyperexcitability (LTH) in the sensory neurons that mediate the responses. Using the cluster of nociceptive sensory neurons inAplysia californicaas a model, we are examining how inflammation induces LTH. A general inflammatory response was induced by inserting a gauze pad into the animal. Within 4 days, the gauze is enmeshed in an amorphous material that contains hemocytes, which comprise a cellular immune system. Concurrently, LTH appears in both ipsilateral and contralateral sensory neurons. The LTH is manifest as increased action potential discharge to a normalized stimulus. Immunocytochemistry revealed that hemocytes have antigens recognized by antibodies to TGFβ1, IL-6, and 5HT. When a localized inflammation was elicited on a nerve, hemocytes containing the TGFβ1 antigen were present near axons within the nerve and those containing...
... ing the cells on a DeLaval continuous flow centrifuge, the lipids were extracted from the cel... more ... ing the cells on a DeLaval continuous flow centrifuge, the lipids were extracted from the cells with chloroform-methanol (1 :I, v/v), and were partially purified on a column of silicic acid by the technique of Vorbeck and Xlarinetti (X), which has been confirmed by Rouser et al. ...
It was found previously that transection of one branch of the bifurcate axon of a giant serotoner... more It was found previously that transection of one branch of the bifurcate axon of a giant serotonergic neuron of Aplysia causes a proportionate decrease in the export of transmitter storage vesicles from the cell body, despite the ability of the remaining branch to transport all of the vesicles normally exported (Aletta and Goldberg, 1982). We report here evidence that this down-regulation is achieved by a decrease in the production of vesicles, rather than a slowing of the processing of vesicles for export from the cell body. Counts of serotonergic vesicles in the cell body show that the size of the somal pool of vesicles is not increased at a time when their rate of export has been halved. Also, transection of one or both branches of the axon decreases the amount of 3H-fucose incorporated during a short period into a putative vesicle membrane glycoprotein but not into other glycoproteins. The results indicate that axotomy should be a useful technique for studying the mechanism of re...
The cell body of R2, a giant cholinergic neuron of Aplysia californica, resides in the abdominal ... more The cell body of R2, a giant cholinergic neuron of Aplysia californica, resides in the abdominal ganglion, whereas its synapses are on thousands of unicellular mucus glands located in the skin. Due to the great spatial separation between the site of macromolecular synthesis and the presynaptic terminals, rapid axonal transport can be used to segregate synaptic proteins from those to be used elsewhere in the cell. The proteins of R2 were labeled by incubating the abdominal ganglion in [35S]methionine for 5 hr in a chamber separated from the rest of the isolated central nervous system. After 50 hr, 28 radiolabeled proteins were reproducibly found by one- and two- dimensional polyacrylamide gel electrophoresis to be transported to the distal regions of peripheral nerves P6, P7, and P8 that innervate the parapodia and middle body wall. We are sure that R2 is the source of these proteins since radioautography of sections taken throughout the nervous system, complemented by cobalt tracing...
The neuron is a highly differentiated cell consisting of distinct regions—cell body, axon, termin... more The neuron is a highly differentiated cell consisting of distinct regions—cell body, axon, terminal—that differ in structure and function. It is likely that characteristic differences in macromolecular composition underlie regional differentiation. Because synthesis of macromolecules occurs primarily, if not exclusively, in the cell body, there are constraints on how regional biochemical differences might be established. We can think of three mechanisms: (1) differential export of macromolecules from the cell body and subsequent selective axonal transport to terminals; (2) selective import from enveloping glial cells; and (3) specific modifications of macromolecules in the axon or at terminals. There is much evidence to support the first mechanism (Ambron et al., 1974a; Dahlstrom, 1971; Ochs, 1972). As for the second, transfer of materials between glial cells and neurons has frequently been postulated (Singer, 1968), but only recently was it convincingly demonstrated (Lasek et al., 1977). Finally, there is some evidence for modification of macromolecules by glycosylation at synapses in mouse brain (Dutton et al., 1973) and in Aplysia axons (Ambron and Treistman, 1977) (also see below).
Over the last two decades, the autogenous venous nerve conduit (AVNC) has been established as an ... more Over the last two decades, the autogenous venous nerve conduit (AVNC) has been established as an effective treatment modality for the repair of nerve gaps less than 3 cm. In this study, the spatial-temporal progression of Schwann-cell migration and peripheral-nerve regeneration across a 10-mm gap bridged by a venous conduit was examined, using immunoctyochemical techniques. Histologic analysis revealed that the process of nerve regeneration through an AVNC occurs in four phases: the hematoma phase, cellular migration phase, axonal advancement phase, and myelination and maturation phase. The authors found that: 1) the lumen of the vein conduit remains patent throughout the process of nerve regeneration; 2) Schwann cells migrate into the vital space of the vessel lumen from the proximal and distal nerve stumps; 3) axonal growth into the conduit lags behind Schwann-cell migration; 4) Schwann cells migrate to the regenerating axons to form mature nodes of Ranvier when the distal stump is present; and 5) mechanical injury alone is sufficient to induce axonal outgrowth from the proximal nerve stump.
The original article to which this Erratum refers was published inJournal of Neurobiology (2003) ... more The original article to which this Erratum refers was published inJournal of Neurobiology (2003) 57(2) 204–220The name of the third author of this article was spelled incorrectly. It should read:Ying‐Ju SungThe publisher regrets this error.
Injury to a peripheral nerve initiates changes that can lead to regeneration of the damaged axons... more Injury to a peripheral nerve initiates changes that can lead to regeneration of the damaged axons. How information about a distant injury is communicated to the cell body is not clear. Using the nervous system of Aplysia californica, we tested the idea that some of this information is conveyed via positive injury signals-axoplasmic proteins that are activated at the injury site and transported to the cell soma. We collected these proteins by crushing pedal nerves and then placing a ligation proximal to the ligation. The contralateral nerves were ligated as controls. Twenty h later, axoplasm was extruded from the nerve segment just distal to the ligation on the crushed nerves (cr/lig) and on the control nerves (lig). The total proteins were rhodaminated and injected into the cytoplasm of neurons in vitro to look for nuclear import. Punctate fluorescence was detected in the nucleus of all seven neurons injected with the cr/lig axoplasm. Only two of five neurons injected with lig axoplasm had any fluorescence. Equal amounts of cr/lig and lig axoplasm were then injected directly into the cell bodies of neurons maintained in vitro. The cells injected with cr/lig axoplasm exhibited renewed growth and significantly longer survival: 25.9 +/- 2.1 days (mean +/- SEM: n = 22) relative to the cells injected with lig axoplasm (15.3 +/- 1.2 days; n = 14) and to those that were not injected (12.2 +/- 1.7 days; n = 24). Fractionation of the cr/lig axoplasm indicated that different factors are responsible for growth and survival.
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