We report that cell survival after neurite transection in a mammalian neuronal model (cultured B1... more We report that cell survival after neurite transection in a mammalian neuronal model (cultured B104 cells) critically depends on somal [Ca2+]i, a novel result that reconciles separate long-standing observations that somal survival decreases with more-proximal axonal transections and that increased somal Ca2+ is cytotoxic. Using fluorescence microscopy, we demonstrate that extracellular Ca2+ at the site of plasmalemmal transection is necessary to form a plasmalemmal barrier, and that other divalent ions (Ba2+, Mg2+) do not play a major role. We also show that extracellular Ca2+, rather than injury per se, initiates the formation of a plasmalemmal barrier and that a transient increase in somal [Ca2+]i significantly decreases the percentage of cells that survive neurite transection. Furthermore, we show that the increased somal [Ca2+]i and decreased cell survival following proximal transections are not due to less frequent or slower plasmalemmal sealing or Ca2+ entry through plasmalemm...
Background: Traumatic neuropathies (TN) are a common source of morbidity in the United States aff... more Background: Traumatic neuropathies (TN) are a common source of morbidity in the United States affecting approximately 5% of all admissions to a level one trauma center. It has been reported that less than 50% of these injuries will obtain a functional recovery and less than 5% will obtain a full recovery. We sought to improve the rate of physiologic recovery following repair of transected nerves using hydrophilic polymers. This technique is based on the ability to fuse axons of severed cell membranes using hydrophilic polymers, generating functional and morphological neuronal continuity. Our hypothesis is that nerve gaps can be acutely repaired using autografts and a double fusion technique if performed before the onset of Wallerian degeneration. Our technique may be applicable for cases of segmental nerve loss including patients with acute traumatic deficits and also patients in need of reconstruction after oncologic resection. Methods: Sprague Dawley rats were anesthetized with is...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994
Transected axons are often assumed to seal at their cut ends by the formation of continuous membr... more Transected axons are often assumed to seal at their cut ends by the formation of continuous membrane barriers that allow for the restoration of function in the axonal stumps. We have used several electrophysiological measures (membrane potential, input resistance, injury current density) and several morphological measures (phase-contrast, video-enhanced differential interference contrast, light, and electron microscopies) of living and fixed material to assess the extent and mechanism of sealing within hours after transecting giant axons of squid (Loligo pealei and Sepioteuthis lessoniana) and earthworms (Lumbricus terrestris). Our electrophysiological data suggest that the proximal and distal ends of transected squid giant axons do not completely seal within 2.5 hr in physiological saline. In contrast, the same set of measures suggest that proximal and distal ends of transected earthworm giant axons seal within 1 hr in physiological saline. Our morphological data show that the cut ...
A variety of effects have been attributed to phytoestrogens, which are present in variable concen... more A variety of effects have been attributed to phytoestrogens, which are present in variable concentrations in soy-based laboratory animal diets. The authors review the inherent complexities in evaluating the effects of soy and dietary phytoestrogens on various in vitro and in vivo systems.
ABSTRACT One important goal of neuroscientists is to eventually understand complex behavioral ada... more ABSTRACT One important goal of neuroscientists is to eventually understand complex behavioral adaptations of humans and other animals as explained by the structure and function of their brain tissues and principles of evolutionary biology. To this end, the dominant model in evolutionary psychology assumes that complex adaptations involving brain or any other tissue are precisely crafted for a specific function and are produced by genes whose alleles all have equal fitness (genetic homomorphism) because sexual recombination would disrupt adaptations produced by genes whose alleles have unequal fitness (genetic polymorphism). This genetically zoomorphic model maintains that humans and other animals have evolved universal neuronal circuits and behavioral adaptations, which in their sum constitute a species-typical nature (a universal human nature for Homo sapiens), and that almost all variation in adaptive behavior among same-sex individuals is due to environmental effects. Alternatively, we assert that a review of currently available data in neuroscience, biology, and psychology strongly suggests that complex adaptations involving brain and other tissues have many imperfections, different functions in different environments, and much polymorphism genetic variation. Our genetically polymorphic model accounts for all these data and predicts that humans and other animal species have evolved many nonuniversal complex behaviors (multiple species-typical behaviors or “human natures”) that differ genetically between males and females, as well as within males and within females. Variability in same-sex behavior is therefore due to both environmental and genetic variation. Our genetically polymorphic model reconciles fundamental assumptions of evolutionary psychology with basic principles of evolutionary biology, behavioral genetics, and neuroscience.
Proceedings of the National Academy of Sciences, 1990
We are able to morphologically fuse the severed halves of an invertebrate-myelinated axon by appl... more We are able to morphologically fuse the severed halves of an invertebrate-myelinated axon by application of polyethylene glycol (PEG) to closely apposed cut ends. Morphological fusion of the medial giant axon (MGA) of the earthworm Lumbricus terrestris is defined as axoplasmic and axolemmal continuity in serial longitudinal sections of MGAs taken through the fusion site as viewed with light or electron microscopes. Morphological continuity is also shown by the transfer of Lucifer yellow dye between apposed MGA segments fused with PEG, but not between apposed MGA segments in normal or hypotonic saline without PEG application. PEG-induced MGA fusion rates can be as high as 80-100% with an appropriate choice of PEG concentration and molecular mass, tight apposition and careful alignment of the cut ends, and treatment with hypotonic salines containing reduced calcium and increased magnesium. A variant of this technique might produce rapid repair of severed mammalian-myelinated axons.
Proceedings of the National Academy of Sciences, 1985
Intracellular recordings were used to demonstrate the occurrence and to analyze the microphysiolo... more Intracellular recordings were used to demonstrate the occurrence and to analyze the microphysiology of long-term synaptic potentiation (LTP) in the crayfish opener neuromuscular synapse. Brief stimulation of the single excitor motor axon enhanced the amplitudes of subsequent postsynaptic potentials for several hours. Three methods of quantal analysis were used to evaluate the mechanism responsible for LTP. The results of all three methods supported predictions of the hypothesis that LTP results from a presynaptic mechanism that increases the average of neurotransmitter quanta evoked by nerve impulses in the excitor axon.
We report that cell survival after neurite transection in a mammalian neuronal model (cultured B1... more We report that cell survival after neurite transection in a mammalian neuronal model (cultured B104 cells) critically depends on somal [Ca2+]i, a novel result that reconciles separate long-standing observations that somal survival decreases with more-proximal axonal transections and that increased somal Ca2+ is cytotoxic. Using fluorescence microscopy, we demonstrate that extracellular Ca2+ at the site of plasmalemmal transection is necessary to form a plasmalemmal barrier, and that other divalent ions (Ba2+, Mg2+) do not play a major role. We also show that extracellular Ca2+, rather than injury per se, initiates the formation of a plasmalemmal barrier and that a transient increase in somal [Ca2+]i significantly decreases the percentage of cells that survive neurite transection. Furthermore, we show that the increased somal [Ca2+]i and decreased cell survival following proximal transections are not due to less frequent or slower plasmalemmal sealing or Ca2+ entry through plasmalemm...
Background: Traumatic neuropathies (TN) are a common source of morbidity in the United States aff... more Background: Traumatic neuropathies (TN) are a common source of morbidity in the United States affecting approximately 5% of all admissions to a level one trauma center. It has been reported that less than 50% of these injuries will obtain a functional recovery and less than 5% will obtain a full recovery. We sought to improve the rate of physiologic recovery following repair of transected nerves using hydrophilic polymers. This technique is based on the ability to fuse axons of severed cell membranes using hydrophilic polymers, generating functional and morphological neuronal continuity. Our hypothesis is that nerve gaps can be acutely repaired using autografts and a double fusion technique if performed before the onset of Wallerian degeneration. Our technique may be applicable for cases of segmental nerve loss including patients with acute traumatic deficits and also patients in need of reconstruction after oncologic resection. Methods: Sprague Dawley rats were anesthetized with is...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994
Transected axons are often assumed to seal at their cut ends by the formation of continuous membr... more Transected axons are often assumed to seal at their cut ends by the formation of continuous membrane barriers that allow for the restoration of function in the axonal stumps. We have used several electrophysiological measures (membrane potential, input resistance, injury current density) and several morphological measures (phase-contrast, video-enhanced differential interference contrast, light, and electron microscopies) of living and fixed material to assess the extent and mechanism of sealing within hours after transecting giant axons of squid (Loligo pealei and Sepioteuthis lessoniana) and earthworms (Lumbricus terrestris). Our electrophysiological data suggest that the proximal and distal ends of transected squid giant axons do not completely seal within 2.5 hr in physiological saline. In contrast, the same set of measures suggest that proximal and distal ends of transected earthworm giant axons seal within 1 hr in physiological saline. Our morphological data show that the cut ...
A variety of effects have been attributed to phytoestrogens, which are present in variable concen... more A variety of effects have been attributed to phytoestrogens, which are present in variable concentrations in soy-based laboratory animal diets. The authors review the inherent complexities in evaluating the effects of soy and dietary phytoestrogens on various in vitro and in vivo systems.
ABSTRACT One important goal of neuroscientists is to eventually understand complex behavioral ada... more ABSTRACT One important goal of neuroscientists is to eventually understand complex behavioral adaptations of humans and other animals as explained by the structure and function of their brain tissues and principles of evolutionary biology. To this end, the dominant model in evolutionary psychology assumes that complex adaptations involving brain or any other tissue are precisely crafted for a specific function and are produced by genes whose alleles all have equal fitness (genetic homomorphism) because sexual recombination would disrupt adaptations produced by genes whose alleles have unequal fitness (genetic polymorphism). This genetically zoomorphic model maintains that humans and other animals have evolved universal neuronal circuits and behavioral adaptations, which in their sum constitute a species-typical nature (a universal human nature for Homo sapiens), and that almost all variation in adaptive behavior among same-sex individuals is due to environmental effects. Alternatively, we assert that a review of currently available data in neuroscience, biology, and psychology strongly suggests that complex adaptations involving brain and other tissues have many imperfections, different functions in different environments, and much polymorphism genetic variation. Our genetically polymorphic model accounts for all these data and predicts that humans and other animal species have evolved many nonuniversal complex behaviors (multiple species-typical behaviors or “human natures”) that differ genetically between males and females, as well as within males and within females. Variability in same-sex behavior is therefore due to both environmental and genetic variation. Our genetically polymorphic model reconciles fundamental assumptions of evolutionary psychology with basic principles of evolutionary biology, behavioral genetics, and neuroscience.
Proceedings of the National Academy of Sciences, 1990
We are able to morphologically fuse the severed halves of an invertebrate-myelinated axon by appl... more We are able to morphologically fuse the severed halves of an invertebrate-myelinated axon by application of polyethylene glycol (PEG) to closely apposed cut ends. Morphological fusion of the medial giant axon (MGA) of the earthworm Lumbricus terrestris is defined as axoplasmic and axolemmal continuity in serial longitudinal sections of MGAs taken through the fusion site as viewed with light or electron microscopes. Morphological continuity is also shown by the transfer of Lucifer yellow dye between apposed MGA segments fused with PEG, but not between apposed MGA segments in normal or hypotonic saline without PEG application. PEG-induced MGA fusion rates can be as high as 80-100% with an appropriate choice of PEG concentration and molecular mass, tight apposition and careful alignment of the cut ends, and treatment with hypotonic salines containing reduced calcium and increased magnesium. A variant of this technique might produce rapid repair of severed mammalian-myelinated axons.
Proceedings of the National Academy of Sciences, 1985
Intracellular recordings were used to demonstrate the occurrence and to analyze the microphysiolo... more Intracellular recordings were used to demonstrate the occurrence and to analyze the microphysiology of long-term synaptic potentiation (LTP) in the crayfish opener neuromuscular synapse. Brief stimulation of the single excitor motor axon enhanced the amplitudes of subsequent postsynaptic potentials for several hours. Three methods of quantal analysis were used to evaluate the mechanism responsible for LTP. The results of all three methods supported predictions of the hypothesis that LTP results from a presynaptic mechanism that increases the average of neurotransmitter quanta evoked by nerve impulses in the excitor axon.
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Papers by George Bittner