We thank Drs. Eric Frank and Paul Brown for useful comments on the manuscript and Dr. Brown for h... more We thank Drs. Eric Frank and Paul Brown for useful comments on the manuscript and Dr. Brown for his participation in the initial experiment of this series.
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)
Three physiologically characterized spindle (group la) afferents were labeled by the intracellula... more Three physiologically characterized spindle (group la) afferents were labeled by the intracellular injection of HRP and were processed for light-level reconstruction.
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 ...
1. The action of peripheral nerve volleys on the polarization of presynaptic terminals of inactiv... more 1. The action of peripheral nerve volleys on the polarization of presynaptic terminals of inactive sensory fibres in cat lumbar spinal cord has been investigated by recording (a) the dorsal root potential (DRP), (b) intracellular changes in polarization of single preterminal axons (PAD or PAH), and (c) changes in excitability of populations of preterminal axons. 2. Presynaptic hyperpolarization (positive DRP-PAH) can be evoked by stimulation of muscle group III afferents as well as by volleys in cutaneous Aft, Ad and C afferents. These volleys can also produce presynaptic depolarization (negative DRP-PAD). 3. The positive DRP is observed in the decerebrate state and increases in amplitude following spinalization. 4. Picrotoxin blocks the positive DRP at the same dosages required to block the negative DRP. Test negative DRPs are depressed during a conditioning positive DRP. These results are used to support earlier suggestions that the positive DRP results from inhibition of interneurones mediating the negative DRP. 5. Trains of group III stimuli at 20/sec evoke a steady positive DRP. Trains of the same intensity at 200/sec evoke a phasic negative DRP. This frequency dependence is observed for PAD and PAH in single sensory axons. 6. The DRPs recorded from different dorsal root filaments in response to a given stimulus vary widely in the ratio of negative to positive DRP. 7. Intracellular recording from single axons reveals that the same stimuli evoke widely varying ratios of PAD and PAH. 8. Stimulation of FRA evokes PAH > PAD in PBST group I afferents, LORNE MENDELL PAD > PAH in sural A fibres and intermediate effects in G-S group I units. 9. It is suggested that activation of flexor reflex afferents may selectively potentiate the synaptic efficacy of large muscle afferents mediating the flexor reflex rather than large skin afferents or large afferents from extensor muscles.
Work early in the last century emphasized the stereotyped activity of spinal circuits based on st... more Work early in the last century emphasized the stereotyped activity of spinal circuits based on studies of reflexes. However, the last several decades have focused on the plasticity of these spinal circuits. These considerations began with studies of the effects of monoamines on descending and reflex circuits. In recent years new classes of compounds called growth factors that are found in peripheral nerves and the spinal cord have been shown to affect circuit behavior in the spinal cord. In this review we will focus on the effects of neurotrophins, particularly nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on spinal circuits. We also discuss evidence that these molecules can modify functions including nociceptive behavior, motor reflexes and stepping behavior. Since these substances and their receptors are normally present in the spinal cord, they could potentially be useful in improving function in disease states and after injury. Here we review recent findings relevant to these translational issues.
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.
We examined whether elevating levels of neurotrophin-3 (NT-3) in the spinal cord and dorsal root ... more We examined whether elevating levels of neurotrophin-3 (NT-3) in the spinal cord and dorsal root ganglion (DRG) would alter connections made by muscle spindle afferent fibers on motoneurons. Adeno-associated virus (AAV) serotypes AAV1, AAV2 and AAV5, selected for their tropism profile, were engineered with the NT-3 gene and administered to the medial gastrocnemius muscle in adult rats. ELISA studies in muscle, DRG and spinal cord revealed that NT-3 concentration in all tissues peaked about 3 months after a single viral injection; after 6 months NT-3 concentration returned to normal values. Intracellular recording in triceps surae motoneurons revealed complex electrophysiological changes. Moderate elevation in cord NT-3 resulted in diminished segmental excitatory postsynaptic potential (EPSP) amplitude, perhaps as a result of the observed decrease in motoneuron input resistance. With further elevation in NT-3 expression, the decline in EPSP amplitude was reversed indicating that NT-3 at higher concentration could increase EPSP amplitude. No correlation was observed between EPSP amplitude and NT-3 concentration in the DRG. Treatment with control viruses could elevate NT-3 levels minimally resulting in measurable electrophysiological effects, perhaps as a result of inflammation associated with injection. EPSPs elicited by stimulation of the ventrolateral funiculus underwent a consistent decline in amplitude independent of NT-3 level. These novel correlations between modified NT-3 expression and single-cell electrophysiological parameters indicate that intramuscular administration of AAV(NT-3) can exert long lasting effects on synaptic transmission to motoneurons. This approach to neurotrophin delivery could be useful in modifying spinal function after injury.
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.
The peripheral nervous system (PNS) has classically been separated into a somatic division compos... more The peripheral nervous system (PNS) has classically been separated into a somatic division composed of both afferent and efferent pathways and an autonomic division containing only efferents. J. N. Langley, who codified this asymmetrical plan at the beginning of the twentieth century, considered different afferents, including visceral ones, as candidates for inclusion in his concept of the "autonomic nervous system" (ANS), but he finally excluded all candidates for lack of any distinguishing histological markers. Langley's classification has been enormously influential in shaping modern ideas about both the structure and the function of the PNS. We survey recent information about the PNS and argue that many of the sensory neurons designated as "visceral" and "somatic" are in fact part of a histologically distinct group of afferents concerned primarily autonomic function. These afferents have traditionally been known as "small dark" neurons or B-neurons. In this target article we outline an association between autonomic and B-neurons based on ontogeny, cell phenotype, and functional relations, grouping them together as part of a common reflex system involved in homeostasis. This more parsimonious classification of the PNS, made possible by the identification of a group of afferents associated primarily with the ANS, avoids a number of confusions produced by the classical orientation. It may also have practical implications for an understanding of nociception, homeostatic reflexes, and the evolution of the nervous system.
We thank Drs. Eric Frank and Paul Brown for useful comments on the manuscript and Dr. Brown for h... more We thank Drs. Eric Frank and Paul Brown for useful comments on the manuscript and Dr. Brown for his participation in the initial experiment of this series.
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)
Three physiologically characterized spindle (group la) afferents were labeled by the intracellula... more Three physiologically characterized spindle (group la) afferents were labeled by the intracellular injection of HRP and were processed for light-level reconstruction.
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 ...
1. The action of peripheral nerve volleys on the polarization of presynaptic terminals of inactiv... more 1. The action of peripheral nerve volleys on the polarization of presynaptic terminals of inactive sensory fibres in cat lumbar spinal cord has been investigated by recording (a) the dorsal root potential (DRP), (b) intracellular changes in polarization of single preterminal axons (PAD or PAH), and (c) changes in excitability of populations of preterminal axons. 2. Presynaptic hyperpolarization (positive DRP-PAH) can be evoked by stimulation of muscle group III afferents as well as by volleys in cutaneous Aft, Ad and C afferents. These volleys can also produce presynaptic depolarization (negative DRP-PAD). 3. The positive DRP is observed in the decerebrate state and increases in amplitude following spinalization. 4. Picrotoxin blocks the positive DRP at the same dosages required to block the negative DRP. Test negative DRPs are depressed during a conditioning positive DRP. These results are used to support earlier suggestions that the positive DRP results from inhibition of interneurones mediating the negative DRP. 5. Trains of group III stimuli at 20/sec evoke a steady positive DRP. Trains of the same intensity at 200/sec evoke a phasic negative DRP. This frequency dependence is observed for PAD and PAH in single sensory axons. 6. The DRPs recorded from different dorsal root filaments in response to a given stimulus vary widely in the ratio of negative to positive DRP. 7. Intracellular recording from single axons reveals that the same stimuli evoke widely varying ratios of PAD and PAH. 8. Stimulation of FRA evokes PAH > PAD in PBST group I afferents, LORNE MENDELL PAD > PAH in sural A fibres and intermediate effects in G-S group I units. 9. It is suggested that activation of flexor reflex afferents may selectively potentiate the synaptic efficacy of large muscle afferents mediating the flexor reflex rather than large skin afferents or large afferents from extensor muscles.
Work early in the last century emphasized the stereotyped activity of spinal circuits based on st... more Work early in the last century emphasized the stereotyped activity of spinal circuits based on studies of reflexes. However, the last several decades have focused on the plasticity of these spinal circuits. These considerations began with studies of the effects of monoamines on descending and reflex circuits. In recent years new classes of compounds called growth factors that are found in peripheral nerves and the spinal cord have been shown to affect circuit behavior in the spinal cord. In this review we will focus on the effects of neurotrophins, particularly nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on spinal circuits. We also discuss evidence that these molecules can modify functions including nociceptive behavior, motor reflexes and stepping behavior. Since these substances and their receptors are normally present in the spinal cord, they could potentially be useful in improving function in disease states and after injury. Here we review recent findings relevant to these translational issues.
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.
We examined whether elevating levels of neurotrophin-3 (NT-3) in the spinal cord and dorsal root ... more We examined whether elevating levels of neurotrophin-3 (NT-3) in the spinal cord and dorsal root ganglion (DRG) would alter connections made by muscle spindle afferent fibers on motoneurons. Adeno-associated virus (AAV) serotypes AAV1, AAV2 and AAV5, selected for their tropism profile, were engineered with the NT-3 gene and administered to the medial gastrocnemius muscle in adult rats. ELISA studies in muscle, DRG and spinal cord revealed that NT-3 concentration in all tissues peaked about 3 months after a single viral injection; after 6 months NT-3 concentration returned to normal values. Intracellular recording in triceps surae motoneurons revealed complex electrophysiological changes. Moderate elevation in cord NT-3 resulted in diminished segmental excitatory postsynaptic potential (EPSP) amplitude, perhaps as a result of the observed decrease in motoneuron input resistance. With further elevation in NT-3 expression, the decline in EPSP amplitude was reversed indicating that NT-3 at higher concentration could increase EPSP amplitude. No correlation was observed between EPSP amplitude and NT-3 concentration in the DRG. Treatment with control viruses could elevate NT-3 levels minimally resulting in measurable electrophysiological effects, perhaps as a result of inflammation associated with injection. EPSPs elicited by stimulation of the ventrolateral funiculus underwent a consistent decline in amplitude independent of NT-3 level. These novel correlations between modified NT-3 expression and single-cell electrophysiological parameters indicate that intramuscular administration of AAV(NT-3) can exert long lasting effects on synaptic transmission to motoneurons. This approach to neurotrophin delivery could be useful in modifying spinal function after injury.
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.
The peripheral nervous system (PNS) has classically been separated into a somatic division compos... more The peripheral nervous system (PNS) has classically been separated into a somatic division composed of both afferent and efferent pathways and an autonomic division containing only efferents. J. N. Langley, who codified this asymmetrical plan at the beginning of the twentieth century, considered different afferents, including visceral ones, as candidates for inclusion in his concept of the "autonomic nervous system" (ANS), but he finally excluded all candidates for lack of any distinguishing histological markers. Langley's classification has been enormously influential in shaping modern ideas about both the structure and the function of the PNS. We survey recent information about the PNS and argue that many of the sensory neurons designated as "visceral" and "somatic" are in fact part of a histologically distinct group of afferents concerned primarily autonomic function. These afferents have traditionally been known as "small dark" neurons or B-neurons. In this target article we outline an association between autonomic and B-neurons based on ontogeny, cell phenotype, and functional relations, grouping them together as part of a common reflex system involved in homeostasis. This more parsimonious classification of the PNS, made possible by the identification of a group of afferents associated primarily with the ANS, avoids a number of confusions produced by the classical orientation. It may also have practical implications for an understanding of nociception, homeostatic reflexes, and the evolution of the nervous system.
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