Perforated patch clamp recordings were made from 118 voltage clamped (-60 mV), capsaicin-responsi... more Perforated patch clamp recordings were made from 118 voltage clamped (-60 mV), capsaicin-responsive dorsal root ganglion (DRG) cells (<30 microns) maintained in dissociated cell culture (6-24 h). A second puff of capsaicin 10 min later always evoked a substantially smaller inward current than the initial puff (tachyphylaxis). Bath-application of NGF (2, 10 or 100 ng/ml) during the 10-min interval resulted in facilitation of the second response in a dose dependent manner in 67% of cells studied. NT-4/5 exerted similar effects but NT-3 did not. Ten minute pretreatment with NGF increased the initial response to capsaicin. We conclude that NGF acutely conditions the response to capsaicin via direct action on DRG cells. Since the capsaicin receptor (VR1) mediates noxious heat sensitivity of polymodal nociceptors, acute sensitization of the noxious heat response by NGF and NT-4/5 may involve a direct action on VR1.
Transection of the spinal cord initiates a complex series of changes in the distal stump. Studies... more Transection of the spinal cord initiates a complex series of changes in the distal stump. Studies at various levels — single synapses, functional systems - reveal considerable complexity in the changes which occur over time. Some reflexes exhibit depression soon after transection, while others are enhanced. In the period 10–30 days after transection, many systems show enhanced function. There is substantial variability in events occurring at longer intervals. At present it is impossible to make generalizations concerning changes which occur in the various systems whose neural circuitry is in the distal stump.
In order to determine the distribution of antibodies such as anti-NGF following systemic injectio... more In order to determine the distribution of antibodies such as anti-NGF following systemic injection in neonates, immunocytochemical techniques were used to examine the localization of rabbit IgG in rat skin, DRG, and spinal cord after treatments with normal rabbit serum or purified rabbit IgG. Daily subcutaneous injections beginning on postnatal day 2 or on day 15 were given for three days. On the fourth day the animals were sacrificed and tissues were processed for rabbit IgG-IR. In the dorsal and ventral spinal cord, staining intensities suggest a substantial increase in the blood-brain barrier during the first two weeks after birth. Staining intensity in the epidermis of the glabrous skin from the hindpaw was substantially lower than in the adjacent dermis. In addition, IgG infrequently accumulated intracellularly in intensely stained patches in the epidermis. IgG was also able to reach relatively high intracellular concentrations in a small number of sensory neurons. The IgG staining pattern in the skin was similar when anti-NGF itself was administered to the animals. The results are discussed in the context of the effects of anti-NGF on the development of nociceptive afferents.
Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Immediate Increase in ... more Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Immediate Increase in Ia-Motoneuron Synaptic Transmission Caudal to Spinal Cord Transection STEVEN G. NELSON, TIMOTHY C. COLLATOS, ANDRZEJ NIECHAJ, AND ...
The notion of neuronal specificity implies that a neuron has an identity, conferred, for example,... more The notion of neuronal specificity implies that a neuron has an identity, conferred, for example, by its surface chemistry, that permits it to contact a defined subset of postsynaptic neurons. Schematic diagrams of connections between regions of the nervous system generally contain an implicit notion of a precise point-to-point projection. Similarly, the concept of a nucleus to which such a neuron might project is generally considered to encompass a compact group of cells.
The fidelity of impulse propagation through the complex axonal tree en route to the various targe... more The fidelity of impulse propagation through the complex axonal tree en route to the various target cells of that fiber is an important question in neurobiology. Anatomists can trace pathways, but if impulses fail to propagate down to the terminals to release transmitter onto the target cell, there is a significant 'disconnect' between anatomy and physiology. These issues have been studied at length in the spinal cord of the cat where it has proven possible to examine the connections made by afferent fibers on motoneurons under different stimulus conditions. EPSP amplitude varies systematically during high frequency stimulation of the afferents according to the identity of the target motoneuron. This variation is a function of the state of the motoneuron's relation to its peripheral target. It changes after motoneuron axotomy and recovers with reinnervation of the periphery. Neurotrophins delivered to the axotomized motor axons fail to induce recovery. Chronic stimulation of the motor nerve alters muscle properties with coordinated changes in properties of the synapses on motoneurons innervating the stimulated muscle. We cannot yet definitively establish the mechanisms determining synaptic behavior during high frequency stimulation. However, the retrograde regulation of these properties suggests that it is an important variable and thus is worthy of intensive further study.
Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Enhancement in Ia-Moto... more Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Enhancement in Ia-Motoneuron Synaptic Transmission Caudal to Chronic Spinal Cord Transection STEVEN G. NELSON AND LORNE M. MENDELL ...
The excitatory postsynaptic potentials produced in motoneurons by impulses in single afferent fib... more The excitatory postsynaptic potentials produced in motoneurons by impulses in single afferent fibers (Ia) have been recorded with the aid of an averaging computer. These responses were used to map the distribution of the terminals of single fibers within the pool of 300 motoneurons of the medial gastrocnemius muscle. Twelve Ia fibers were studied in separate experiments. Monosynaptic excitatory postsynaptic potentials were found in 94 percent of the 77 motoneurons investigated. This finding indicates that each of the 300 motoneurons must receive afferent fibers from almost all of the spindles of the muscle it innervates.
1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory posts... more 1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory postsynaptic potential (EPSP) amplitude recorded in target motoneurons. This can be either positive (EPSP amplitude increases in response to successive stimuli in the high-frequency burst) or negative (decrease in EPSP amplitude). We have investigated whether the magnitude of modulation is associated with the stimulated afferent, the responding motoneuron, or the amplitude of the EPSP. 2. In agreement with previous findings, we found that positive modulation tends to occur at connections generating small EPSPs and negative modulation, at those producing large EPSPs. Because large EPSPs generally are evoked in motoneurons with low values of rheobase, we found, as anticipated, that connections on low rheobase motoneurons are prone to negative modulation during high-frequency stimulation, whereas those on high rheobase motoneurons (which tend to generate small EPSPs) are prone to positive modulation. 3. In experiments where the projection of multiple afferents to a single motoneuron was studied, we found that amplitude modulation was similar despite differences in EPSP amplitude. Thus in a given motoneuron there is no relationship between modulation and amplitude, in contrast to the existence of such a relationship in the population of connections as a whole. 4. In the converse experiments where the projection of single afferents to multiple motoneurons was studied, we found marked variability in the modulation patterns with clear indications that amplitude and modulation are correlated as in the entire population of Ia/motoneuron connections. 5. We tested the constancy of modulation patterns evoked in a given motoneuron by comparing the modulation patterns evoked in motoneurons by single fibers, and by stimulation of the heteronymous nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Properties of medial gastrocnemius motoneurones in cats were examined with intracellular elect... more 1. Properties of medial gastrocnemius motoneurones in cats were examined with intracellular electrodes 1-77 days after partial transection of the medial gastrocnemius muscle nerve. 2. Three sequential stages of reaction were defined: (i) firstly, conduction velocity of axotomized motoneurones fell, but e.p.s.p. properties and Ia-motoneurone connectivity were normal; (ii) secondly, e.p.s.p.s became characterized by prolonged rise times and half-widths and by diminished amplitudes; (iii) finally, failures of connectivity were also seen, that is, Ia spindle afferent fibres connected with fewer axotomized than normal homonymous motoneurones. 3. The reason for the change of e.p.s.p. properties cannot be stated with certainty: among the factors may be (i) a change of motoneurone membrane properties and morphology; (ii) partial detachment of synaptic boutons before their total disconnexion, and (iii) detachment of Ia afferent branches terminating on the motoneurone soma before those on the dendrites. 4. The previous conclusion that alteration of e.p.s.p. profiles following motoneurone axotomy was due to total disconnexion of those Ia fibres making synapses on the soma and proximal dendrites ("somatic stripping") must be modified to account for the findings that e.p.s.p. changes are seen before connectivity changes.
Perforated patch clamp recordings were made from 118 voltage clamped (-60 mV), capsaicin-responsi... more Perforated patch clamp recordings were made from 118 voltage clamped (-60 mV), capsaicin-responsive dorsal root ganglion (DRG) cells (<30 microns) maintained in dissociated cell culture (6-24 h). A second puff of capsaicin 10 min later always evoked a substantially smaller inward current than the initial puff (tachyphylaxis). Bath-application of NGF (2, 10 or 100 ng/ml) during the 10-min interval resulted in facilitation of the second response in a dose dependent manner in 67% of cells studied. NT-4/5 exerted similar effects but NT-3 did not. Ten minute pretreatment with NGF increased the initial response to capsaicin. We conclude that NGF acutely conditions the response to capsaicin via direct action on DRG cells. Since the capsaicin receptor (VR1) mediates noxious heat sensitivity of polymodal nociceptors, acute sensitization of the noxious heat response by NGF and NT-4/5 may involve a direct action on VR1.
Transection of the spinal cord initiates a complex series of changes in the distal stump. Studies... more Transection of the spinal cord initiates a complex series of changes in the distal stump. Studies at various levels — single synapses, functional systems - reveal considerable complexity in the changes which occur over time. Some reflexes exhibit depression soon after transection, while others are enhanced. In the period 10–30 days after transection, many systems show enhanced function. There is substantial variability in events occurring at longer intervals. At present it is impossible to make generalizations concerning changes which occur in the various systems whose neural circuitry is in the distal stump.
In order to determine the distribution of antibodies such as anti-NGF following systemic injectio... more In order to determine the distribution of antibodies such as anti-NGF following systemic injection in neonates, immunocytochemical techniques were used to examine the localization of rabbit IgG in rat skin, DRG, and spinal cord after treatments with normal rabbit serum or purified rabbit IgG. Daily subcutaneous injections beginning on postnatal day 2 or on day 15 were given for three days. On the fourth day the animals were sacrificed and tissues were processed for rabbit IgG-IR. In the dorsal and ventral spinal cord, staining intensities suggest a substantial increase in the blood-brain barrier during the first two weeks after birth. Staining intensity in the epidermis of the glabrous skin from the hindpaw was substantially lower than in the adjacent dermis. In addition, IgG infrequently accumulated intracellularly in intensely stained patches in the epidermis. IgG was also able to reach relatively high intracellular concentrations in a small number of sensory neurons. The IgG staining pattern in the skin was similar when anti-NGF itself was administered to the animals. The results are discussed in the context of the effects of anti-NGF on the development of nociceptive afferents.
Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Immediate Increase in ... more Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Immediate Increase in Ia-Motoneuron Synaptic Transmission Caudal to Spinal Cord Transection STEVEN G. NELSON, TIMOTHY C. COLLATOS, ANDRZEJ NIECHAJ, AND ...
The notion of neuronal specificity implies that a neuron has an identity, conferred, for example,... more The notion of neuronal specificity implies that a neuron has an identity, conferred, for example, by its surface chemistry, that permits it to contact a defined subset of postsynaptic neurons. Schematic diagrams of connections between regions of the nervous system generally contain an implicit notion of a precise point-to-point projection. Similarly, the concept of a nucleus to which such a neuron might project is generally considered to encompass a compact group of cells.
The fidelity of impulse propagation through the complex axonal tree en route to the various targe... more The fidelity of impulse propagation through the complex axonal tree en route to the various target cells of that fiber is an important question in neurobiology. Anatomists can trace pathways, but if impulses fail to propagate down to the terminals to release transmitter onto the target cell, there is a significant 'disconnect' between anatomy and physiology. These issues have been studied at length in the spinal cord of the cat where it has proven possible to examine the connections made by afferent fibers on motoneurons under different stimulus conditions. EPSP amplitude varies systematically during high frequency stimulation of the afferents according to the identity of the target motoneuron. This variation is a function of the state of the motoneuron's relation to its peripheral target. It changes after motoneuron axotomy and recovers with reinnervation of the periphery. Neurotrophins delivered to the axotomized motor axons fail to induce recovery. Chronic stimulation of the motor nerve alters muscle properties with coordinated changes in properties of the synapses on motoneurons innervating the stimulated muscle. We cannot yet definitively establish the mechanisms determining synaptic behavior during high frequency stimulation. However, the retrograde regulation of these properties suggests that it is an important variable and thus is worthy of intensive further study.
Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Enhancement in Ia-Moto... more Page 1. JOURNALOF NEUROPHYSIOLOGY Vol. 42, No. 3, May 1979. Printed in USA Enhancement in Ia-Motoneuron Synaptic Transmission Caudal to Chronic Spinal Cord Transection STEVEN G. NELSON AND LORNE M. MENDELL ...
The excitatory postsynaptic potentials produced in motoneurons by impulses in single afferent fib... more The excitatory postsynaptic potentials produced in motoneurons by impulses in single afferent fibers (Ia) have been recorded with the aid of an averaging computer. These responses were used to map the distribution of the terminals of single fibers within the pool of 300 motoneurons of the medial gastrocnemius muscle. Twelve Ia fibers were studied in separate experiments. Monosynaptic excitatory postsynaptic potentials were found in 94 percent of the 77 motoneurons investigated. This finding indicates that each of the 300 motoneurons must receive afferent fibers from almost all of the spindles of the muscle it innervates.
1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory posts... more 1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory postsynaptic potential (EPSP) amplitude recorded in target motoneurons. This can be either positive (EPSP amplitude increases in response to successive stimuli in the high-frequency burst) or negative (decrease in EPSP amplitude). We have investigated whether the magnitude of modulation is associated with the stimulated afferent, the responding motoneuron, or the amplitude of the EPSP. 2. In agreement with previous findings, we found that positive modulation tends to occur at connections generating small EPSPs and negative modulation, at those producing large EPSPs. Because large EPSPs generally are evoked in motoneurons with low values of rheobase, we found, as anticipated, that connections on low rheobase motoneurons are prone to negative modulation during high-frequency stimulation, whereas those on high rheobase motoneurons (which tend to generate small EPSPs) are prone to positive modulation. 3. In experiments where the projection of multiple afferents to a single motoneuron was studied, we found that amplitude modulation was similar despite differences in EPSP amplitude. Thus in a given motoneuron there is no relationship between modulation and amplitude, in contrast to the existence of such a relationship in the population of connections as a whole. 4. In the converse experiments where the projection of single afferents to multiple motoneurons was studied, we found marked variability in the modulation patterns with clear indications that amplitude and modulation are correlated as in the entire population of Ia/motoneuron connections. 5. We tested the constancy of modulation patterns evoked in a given motoneuron by comparing the modulation patterns evoked in motoneurons by single fibers, and by stimulation of the heteronymous nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Properties of medial gastrocnemius motoneurones in cats were examined with intracellular elect... more 1. Properties of medial gastrocnemius motoneurones in cats were examined with intracellular electrodes 1-77 days after partial transection of the medial gastrocnemius muscle nerve. 2. Three sequential stages of reaction were defined: (i) firstly, conduction velocity of axotomized motoneurones fell, but e.p.s.p. properties and Ia-motoneurone connectivity were normal; (ii) secondly, e.p.s.p.s became characterized by prolonged rise times and half-widths and by diminished amplitudes; (iii) finally, failures of connectivity were also seen, that is, Ia spindle afferent fibres connected with fewer axotomized than normal homonymous motoneurones. 3. The reason for the change of e.p.s.p. properties cannot be stated with certainty: among the factors may be (i) a change of motoneurone membrane properties and morphology; (ii) partial detachment of synaptic boutons before their total disconnexion, and (iii) detachment of Ia afferent branches terminating on the motoneurone soma before those on the dendrites. 4. The previous conclusion that alteration of e.p.s.p. profiles following motoneurone axotomy was due to total disconnexion of those Ia fibres making synapses on the soma and proximal dendrites ("somatic stripping") must be modified to account for the findings that e.p.s.p. changes are seen before connectivity changes.
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