Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the a... more Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the accessory planta retractor muscles (APRMs) in proleg-bearing abdominal segment 3 and their homologs in non-proleg-bearing abdominal segment 2. In pupae, these APRMs exhibit a rhythmic 'pupal motor pattern' in which all four muscles contract synchronously at approximately 4 s intervals for long bouts, without externally visible movements. On the basis of indirect evidence, it was proposed previously that APRM contractions during the pupal motor pattern circulate hemolymph in the developing wings and legs. This hypothesis was tested in the present study by making simultaneous electromyographic recordings of APRM activity and contact thermographic recordings of hemolymph flow in pupal wings. APRM contractions and hemolymph flow were strictly correlated during the pupal motor pattern. The proposed circulatory mechanism was further supported by the findings that unilateral ablation of ...
Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the a... more Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the accessory planta retractor muscles (APRMs) in proleg-bearing abdominal segment 3 and their homologs in non-proleg-bearing abdominal segment 2. In pupae, these APRMs exhibit a rhythmic 'pupal motor pattern' in which all four muscles contract synchronously at approximately 4 s intervals for long bouts, without externally visible movements. On the basis of indirect evidence, it was proposed previously that APRM contractions during the pupal motor pattern circulate hemolymph in the developing wings and legs. This hypothesis was tested in the present study by making simultaneous electromyographic recordings of APRM activity and contact thermographic recordings of hemolymph flow in pupal wings. APRM contractions and hemolymph flow were strictly correlated during the pupal motor pattern. The proposed circulatory mechanism was further supported by the findings that unilateral ablation of ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1999
Terminal Schwann cells (TSCs), neuroglia that cover motoneuron terminals, play a role in regulati... more Terminal Schwann cells (TSCs), neuroglia that cover motoneuron terminals, play a role in regulating the structure and function of the neuromuscular junction. In rats, the number of TSCs at each junction increases rapidly in early postnatal life and more slowly in young adults. It is possible that TSC number increases to match increasing endplate area. Alternatively, the increase in TSC number may reflect a developmental process independent of endplate size or terminal function. To experimentally test the relationship between endplate size and TSC number, we manipulated endplate area in an androgen-sensitive muscle of the rat, the levator ani (LA), by castration and by androgen replacement. We found that TSC number not only increased as endplates enlarged but also decreased when endplates shrank. Ninety days after castration, TSC number decreased by approximately 20% (one cell per junction) as endplate size decreased by 30%. These effects were reversed by testosterone. Testosterone l...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1999
Mature motoneurons respond to partial denervation of their target muscle by sprouting to reinnerv... more Mature motoneurons respond to partial denervation of their target muscle by sprouting to reinnervate denervated fibers, thus maintaining muscle strength in the face of motoneuronal loss caused by injury or disease. Neonatal motoneurons, however, do not expand to innervate more muscle fibers. The present work seeks to understand this developmental change in motoneuron response to partial denervation. It has been suggested that neonatal motor units cannot increase in size because they are already at their maximum size (approximately five times larger than in adulthood). We ruled out this explanation by showing that after partial denervation on postnatal day 14 (P14), when motor units have decreased to their adult size, motoneurons still did not sprout to reinnervate as many fibers as in adulthood. Instead, we found evidence supporting an alternative explanation involving terminal Schwann cells. After partial denervation of neonatal (but not adult) muscles, terminal Schwann cells at de...
Specific neuronal circuits within the vertebrate nervous system express high levels of steroid re... more Specific neuronal circuits within the vertebrate nervous system express high levels of steroid receptors and are sensitive to the effects of steroid hormones. The mechanisms by which these neuronal circuits develop their unique steroid sensitivity are unknown. One intriguing hypothesis is that retrograde influences during early postnatal life play a role in determining which central nervous system (CNS) neurons become sensitive to steroids. We now present evidence that during a critical period in early postnatal development, axonal injury disrupts the normal development of steroid sensitivity. The spinal nucleus of the bulbocavernosus (SNB) is a neuromuscular system that is highly androgen-sensitive at the level of both the motoneurons and their target muscles. Testosterone levels regulate the size of SNB motoneurons and their muscles in adult rats. Cutting the axons of SNB motoneurons on postnatal day 14 (P14) caused permanent decreases in SNB motoneuronal soma size, as well as in ...
Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the a... more Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the accessory planta retractor muscles (APRMs) in proleg-bearing abdominal segment 3 and their homologs in non-proleg-bearing abdominal segment 2. In pupae, these APRMs exhibit a rhythmic 'pupal motor pattern' in which all four muscles contract synchronously at approximately 4 s intervals for long bouts, without externally visible movements. On the basis of indirect evidence, it was proposed previously that APRM contractions during the pupal motor pattern circulate hemolymph in the developing wings and legs. This hypothesis was tested in the present study by making simultaneous electromyographic recordings of APRM activity and contact thermographic recordings of hemolymph flow in pupal wings. APRM contractions and hemolymph flow were strictly correlated during the pupal motor pattern. The proposed circulatory mechanism was further supported by the findings that unilateral ablation of ...
During the period of synapse elimination, motoneurons are impaired in their ability to generate o... more During the period of synapse elimination, motoneurons are impaired in their ability to generate or regenerate axonal branches: following partial denervation of their target muscle, young motoneurons do not sprout to nearby denervated fibers and after axonal injury, they fail to reinnervate the muscle. In the rat levator ani (LA) muscle, which is innervated by motoneurons in the spinal nucleus of the bulbocavernosus (SNB), synapse elimination ends relatively late in development and can be regulated by testosterone. We took advantage of this system to determine if the end of synapse elimination and the development of regenerative capabilities by motoneurons share a common mechanism, or, alternatively, if these two events can be dissociated in time. Axotomy on or before postnatal day 14 (P14) caused the death of SNB motoneurons. By P21, toward the end of synapse elimination in the LA muscle, SNB motoneurons had developed the ability to survive axonal injury. Altering testosterone levels by castration on P7 followed by 4 weeks of either testosterone propionate or control injections did not change the ability of SNB motoneurons to survive axonal injury during development, although these same treatments alter the time course of synapse elimination in the LA muscle. Thus, we dissociated the inability of SNB motoneurons to recover from axonal injury from their developmental elimination of synaptic terminals. We also measured the effect of early axotomy on motoneuronal soma size and on target muscle weight. Axotomy on P14 caused a long-lasting decrease in the soma size of surviving SNB motoneurons, whereas motoneurons axotomized on P28 recovered their normal soma size. Axotomy on or before P7 caused severe atrophy of the target muscles, matching the extensive loss of motoneurons. However, target muscle recovery after axotomy on P14 was as good as recovery after axotomy at later ages, despite greater motoneuronal death after axotomy on P14. This result may reflect an increase in motor unit size, a decrease in polyneuronal innervation by SNB motoneurons that survive axotomy on P14, or a combination of the two.
Programmed cell death plays a critical role in sculpting the nervous system during embryonic deve... more Programmed cell death plays a critical role in sculpting the nervous system during embryonic development. In holometabolous insects, cell death also plays an important role in the reorganization of the nervous system during metamorphosis. In Manduca sexta, cell death and the factors that regulate it can be studied at the level of individually identified neurons. The accessory planta retractor (APR) motoneurons undergo segment-specific death during the larval-pupal transformation. APRs in abdominal segments 1, 5, and 6 die at pupation; those in abdominal segments 2, 3, and 4 survive until adulthood. Juvenile hormone and ecdysteroids regulate the metamorphic restructuring of the nervous system, but the factors that determine which APRs will live and which will die are not known. The present study assessed the possible importance of cell-cell interactions in determining APR survival at pupation by removing APR's target muscle or mechanosensory input early in the final larval instar, prior to the hormonal cues that trigger the larval-pupal transformation. The motoneurons showed their normal, segment-specific pattern of death in nearly all cases. These results suggest that target muscles and sensory input play little or no role in determining the segment-specific pattern of APR survival at pupation.
Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the a... more Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the accessory planta retractor muscles (APRMs) in proleg-bearing abdominal segment 3 and their homologs in non-proleg-bearing abdominal segment 2. In pupae, these APRMs exhibit a rhythmic 'pupal motor pattern' in which all four muscles contract synchronously at approximately 4 s intervals for long bouts, without externally visible movements. On the basis of indirect evidence, it was proposed previously that APRM contractions during the pupal motor pattern circulate hemolymph in the developing wings and legs. This hypothesis was tested in the present study by making simultaneous electromyographic recordings of APRM activity and contact thermographic recordings of hemolymph flow in pupal wings. APRM contractions and hemolymph flow were strictly correlated during the pupal motor pattern. The proposed circulatory mechanism was further supported by the findings that unilateral ablation of ...
Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the a... more Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the accessory planta retractor muscles (APRMs) in proleg-bearing abdominal segment 3 and their homologs in non-proleg-bearing abdominal segment 2. In pupae, these APRMs exhibit a rhythmic 'pupal motor pattern' in which all four muscles contract synchronously at approximately 4 s intervals for long bouts, without externally visible movements. On the basis of indirect evidence, it was proposed previously that APRM contractions during the pupal motor pattern circulate hemolymph in the developing wings and legs. This hypothesis was tested in the present study by making simultaneous electromyographic recordings of APRM activity and contact thermographic recordings of hemolymph flow in pupal wings. APRM contractions and hemolymph flow were strictly correlated during the pupal motor pattern. The proposed circulatory mechanism was further supported by the findings that unilateral ablation of ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1999
Terminal Schwann cells (TSCs), neuroglia that cover motoneuron terminals, play a role in regulati... more Terminal Schwann cells (TSCs), neuroglia that cover motoneuron terminals, play a role in regulating the structure and function of the neuromuscular junction. In rats, the number of TSCs at each junction increases rapidly in early postnatal life and more slowly in young adults. It is possible that TSC number increases to match increasing endplate area. Alternatively, the increase in TSC number may reflect a developmental process independent of endplate size or terminal function. To experimentally test the relationship between endplate size and TSC number, we manipulated endplate area in an androgen-sensitive muscle of the rat, the levator ani (LA), by castration and by androgen replacement. We found that TSC number not only increased as endplates enlarged but also decreased when endplates shrank. Ninety days after castration, TSC number decreased by approximately 20% (one cell per junction) as endplate size decreased by 30%. These effects were reversed by testosterone. Testosterone l...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1999
Mature motoneurons respond to partial denervation of their target muscle by sprouting to reinnerv... more Mature motoneurons respond to partial denervation of their target muscle by sprouting to reinnervate denervated fibers, thus maintaining muscle strength in the face of motoneuronal loss caused by injury or disease. Neonatal motoneurons, however, do not expand to innervate more muscle fibers. The present work seeks to understand this developmental change in motoneuron response to partial denervation. It has been suggested that neonatal motor units cannot increase in size because they are already at their maximum size (approximately five times larger than in adulthood). We ruled out this explanation by showing that after partial denervation on postnatal day 14 (P14), when motor units have decreased to their adult size, motoneurons still did not sprout to reinnervate as many fibers as in adulthood. Instead, we found evidence supporting an alternative explanation involving terminal Schwann cells. After partial denervation of neonatal (but not adult) muscles, terminal Schwann cells at de...
Specific neuronal circuits within the vertebrate nervous system express high levels of steroid re... more Specific neuronal circuits within the vertebrate nervous system express high levels of steroid receptors and are sensitive to the effects of steroid hormones. The mechanisms by which these neuronal circuits develop their unique steroid sensitivity are unknown. One intriguing hypothesis is that retrograde influences during early postnatal life play a role in determining which central nervous system (CNS) neurons become sensitive to steroids. We now present evidence that during a critical period in early postnatal development, axonal injury disrupts the normal development of steroid sensitivity. The spinal nucleus of the bulbocavernosus (SNB) is a neuromuscular system that is highly androgen-sensitive at the level of both the motoneurons and their target muscles. Testosterone levels regulate the size of SNB motoneurons and their muscles in adult rats. Cutting the axons of SNB motoneurons on postnatal day 14 (P14) caused permanent decreases in SNB motoneuronal soma size, as well as in ...
Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the a... more Most larval external muscles in Manduca sexta degenerate at pupation, with the exception of the accessory planta retractor muscles (APRMs) in proleg-bearing abdominal segment 3 and their homologs in non-proleg-bearing abdominal segment 2. In pupae, these APRMs exhibit a rhythmic 'pupal motor pattern' in which all four muscles contract synchronously at approximately 4 s intervals for long bouts, without externally visible movements. On the basis of indirect evidence, it was proposed previously that APRM contractions during the pupal motor pattern circulate hemolymph in the developing wings and legs. This hypothesis was tested in the present study by making simultaneous electromyographic recordings of APRM activity and contact thermographic recordings of hemolymph flow in pupal wings. APRM contractions and hemolymph flow were strictly correlated during the pupal motor pattern. The proposed circulatory mechanism was further supported by the findings that unilateral ablation of ...
During the period of synapse elimination, motoneurons are impaired in their ability to generate o... more During the period of synapse elimination, motoneurons are impaired in their ability to generate or regenerate axonal branches: following partial denervation of their target muscle, young motoneurons do not sprout to nearby denervated fibers and after axonal injury, they fail to reinnervate the muscle. In the rat levator ani (LA) muscle, which is innervated by motoneurons in the spinal nucleus of the bulbocavernosus (SNB), synapse elimination ends relatively late in development and can be regulated by testosterone. We took advantage of this system to determine if the end of synapse elimination and the development of regenerative capabilities by motoneurons share a common mechanism, or, alternatively, if these two events can be dissociated in time. Axotomy on or before postnatal day 14 (P14) caused the death of SNB motoneurons. By P21, toward the end of synapse elimination in the LA muscle, SNB motoneurons had developed the ability to survive axonal injury. Altering testosterone levels by castration on P7 followed by 4 weeks of either testosterone propionate or control injections did not change the ability of SNB motoneurons to survive axonal injury during development, although these same treatments alter the time course of synapse elimination in the LA muscle. Thus, we dissociated the inability of SNB motoneurons to recover from axonal injury from their developmental elimination of synaptic terminals. We also measured the effect of early axotomy on motoneuronal soma size and on target muscle weight. Axotomy on P14 caused a long-lasting decrease in the soma size of surviving SNB motoneurons, whereas motoneurons axotomized on P28 recovered their normal soma size. Axotomy on or before P7 caused severe atrophy of the target muscles, matching the extensive loss of motoneurons. However, target muscle recovery after axotomy on P14 was as good as recovery after axotomy at later ages, despite greater motoneuronal death after axotomy on P14. This result may reflect an increase in motor unit size, a decrease in polyneuronal innervation by SNB motoneurons that survive axotomy on P14, or a combination of the two.
Programmed cell death plays a critical role in sculpting the nervous system during embryonic deve... more Programmed cell death plays a critical role in sculpting the nervous system during embryonic development. In holometabolous insects, cell death also plays an important role in the reorganization of the nervous system during metamorphosis. In Manduca sexta, cell death and the factors that regulate it can be studied at the level of individually identified neurons. The accessory planta retractor (APR) motoneurons undergo segment-specific death during the larval-pupal transformation. APRs in abdominal segments 1, 5, and 6 die at pupation; those in abdominal segments 2, 3, and 4 survive until adulthood. Juvenile hormone and ecdysteroids regulate the metamorphic restructuring of the nervous system, but the factors that determine which APRs will live and which will die are not known. The present study assessed the possible importance of cell-cell interactions in determining APR survival at pupation by removing APR's target muscle or mechanosensory input early in the final larval instar, prior to the hormonal cues that trigger the larval-pupal transformation. The motoneurons showed their normal, segment-specific pattern of death in nearly all cases. These results suggest that target muscles and sensory input play little or no role in determining the segment-specific pattern of APR survival at pupation.
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Papers by J. Lubischer