Signal stabilization and noise suppression in neural systems

Summary Neural activity is viewed as a stochastic point process, in which information resides in the modulation of a background of spontaneous activity. Characteristic features of the spatial and temporal mapping of sensory signals are discussed. One of the puzzling aspects of neural functioning is the integrity of the signal in its passage toward higher brain centers, in view of the fundamentally noisy response of the individual neuron. It is shown, that a process, we call image stabilization, is a direct consequence of the particular mapping function exemplified by lateral inhibition and adaptation.The research reported in this paper was sponsored by the Aerospace Medical Research Laboratories, Aerospace Medical Division, Air Force Systems Command, Wright-Patterson Air Force Base, Ohio, under contract No. F 33615-67-C-1413 and the Office of Naval Research, contract No. ONR N0001467-A-0378-0001, with Syracuse University Research Institute. Further reproduction is authorized to satisfy needs of the U.S. Government.     

The mechanosensory apparatus of the femoral tactile spine of the cockroach,Periplaneta americana

Summary Tactile spines are large cuticular sense organs that appear to provide insects with a sense of touch which is spatially coarse but of great sensitivity. Cockroach legs have a number of these spines on each leg and a particularly prominent spine on the end of each femur, the femoral tactile spine. The ease of recording afferent activity from this spine during mechanical stimulation has made it one of the most thoroughly studied insect mechanoreceptors and yet it has never been examined by electron microscopy.We report here the results of an examination of the femoral tactile spine by both scanning and transmission electron microscopy, as well as by light microscopy. The spine is shown to be innervated by a single sensory bipolar neuron with its soma located in the base of the spine. A canal through the wall of the spine leads to the outside and emerges just above the junction between the base of the spine and its articulating socket membrane. The sensory dendrite of the neuron passes from the soma through this canal and forms a modified ciliary sensory ending with the typical dendritic sheath and dense tubular body that is characteristic of insect mechanosensory cuticular sensilla. The tubular body is embedded in a cuticular terminal plug which closes the exterior end of the canal but appears to be fastened to the spine by a very flexible ring of cuticle. This plug is connected to the socket membrane by a specialized socket attachment which presumably serves to move the plug relative to the wall of the spine during movement of the spine within the socket. The morphology of this sensillum is discussed in terms of the possible ways in which it is stimulated by movements of the spine and also in light of the dynamic behaviour of the receptor which is now very well described.Supported by the Canadian Medical Research Council. The authors gratefully acknowledge the expert technical assistance of Sita Prasad and Rodney Gramlich     

Role of the giant cerebral ganglion neuron in control of defensive behavior ofHelix lucorum

Neurons participating in contraction of the ommatophore retractor ofHelix lucorum were studied by morphological and electrophysiological methods. Staining by the cobalt filling method revealed a giant cerebral ganglion neuron which sends a fiber into the motor branch of the ipsilateral optic nerve. Both spontaneous and evoked contraction of the retractor was shown to be preceded by a volley of action potentials in the giant neuron. The high-frequency volley of impulses evoked by intracellular stimulation of this neuron leads to contraction of the ipsilateral ommatophore retractor; the intensity of this contraction depends on the discharge frequency. The composition of the sensory inputs of the neuron is discussed. A conclusion is drawn on the motor function of this cerebral ganglion neuron in the escape reflex ofH. lucorum.Research Institute for Biological Testing of Chemical Compounds, Ministry of the Medical Industry, Staraya Kupavna, Moscow Province. Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 14, No. 4, pp. 353–358, July–August, 1982.     

Pharmacological evidence for the involvement of the cAMP cascade in sensory fatigue in Drosophila

Summary We have investigated the effect of systemic treatment with drugs that affect the cAMP cascade on the sensory response and sensory fatigue in an identified mechanosensory neuron of Drosophila. Forskolin, an activator of adenylate cyclase, decreases the sensory response of the neuron. H7, an inhibitor of protein kinase, inhibits sensory fatigue. Octopaminergic ligands facilitate sensory fatigue. These results, together with our previous neurogenetic analysis of sensory fatigue in Drosophila (Corfas and Dudai 1990), corroborate the hypothesis that the cAMP cascade is involved in the generation and modulation of sensory fatigue.Abbreviations ANP antero-notopleural (neuron) - CDMF chlordimeform - ISI interstimulus interval     

Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.     

A direct role for Sox10 in specification of neural crest-derived sensory neurons

sox10 is necessary for development of neural and pigment cell derivatives of the neural crest (NC). However, whereas a direct role for Sox10 activity has been established in pigment and glial lineages, this is more controversial in NC-derived sensory neurons of the dorsal root ganglia (DRGs). We proposed that sox10 functioned in specification of sensory neurons, whereas others suggested that sensory neuronal defects were merely secondary to absence of glia. Here we provide evidence that in zebrafish, early DRG sensory neuron survival is independent of differentiated glia. Critically, we demonstrate that Sox10 is expressed transiently in the sensory neuron lineage, and specifies sensory neuron precursors by regulating the proneural gene neurogenin1. Consistent with this, we have isolated a novel sox10 mutant that lacks glia and yet displays a neurogenic DRG phenotype. In conjunction with previous findings, these data establish the generality of our model of Sox10 function in NC fate specification.     

Fine structure and primary sensory projections of sensilla located in the sacculus of the antenna of Drosophila melanogaster

Sensilla lining the inner walls of the sacculus on the third antennal segment of Drosophila melanogaster were studied by light and transmission electron microscopy. The sacculus consists of three chambers: I, II and III. Inside each chamber morphologically distinct groups of sensilla having inflexible sockets were observed. Chamber I contains no-pore sensilla basiconica (np-SB). The lumen of all np-SB are innervated by two neurons, both resembling hygroreceptors. However, a few np-SB contain one additional neuron, presumed to be thermoreceptive. Chamber II houses no-pore sensilla coeloconica (np-SC). All np-SC are innervated by three neurons. The outer dendritic segments of two of these neurons fit tightly to the wall of the lumen and resemble hygroreceptor neurons. A third, more electron-dense sensory neuron, terminates at the base of the sensillum and resembles a thermoreceptor cell. Chamber III of the sacculus is divided into ventral and dorsal compartments, each housing morphologically distinct grooved sensilla (GS). The ventral compartment contains thick GS₁, and the dorsal compartment has slender sensilla GS₂. Ultrastructurally, both GS₁ and GS₂ are doublewalled sensilla with a longitudinal slit-channel system and are innervated by two neurons. The dendritic outer segment of one ofthe two neurons innervates the lumen of the GS and branches. On morphological criteria, we infer this neuron to be olfactory. The other sensory neuron is probably thermoreceptive. Thus, the sacculus in Drosophila has sensilla that are predominantly involved in hygroreception, thermoreception, and olfaction. We have traced the sensory projections of the neurons innervating the sacculus sensilla of chamber III using cobaltous lysine or ethanolic cobalt (II) chloride. The fibres project to the antennal lobes, and at least four glomeruli (VM₃, DA₃ and DL_2-3) are projection areas of sensory neurons from these sensilla. glomerulus DL₂ is a common target for the afferent fibres of the surface sensilla coeloconica and GS, whereas the VM₃, DA₃ and DL₃ glomeruli receive sensory fibres only from the GS.     

Pressure sensation by an anterior pagoda neuron population distributed in multiple ganglia in the leech, Whitmania pigra

Sensory processing of pressure signals in the central nervous system of the leech, Whitmania pigra, was studied through the interaction between pressure sensory neurons and anterior pagoda neurons. The responses of anterior pagoda neurons to one pulse or a train of pulses in pressure sensory neurons were characterized by the latency and amplitude of excitatory postsynaptic potentials. Here we show that each pressure sensory neuron is able to activate all the anterior pagoda neurons throughout the leech central nervous system. The response patterns of all anterior pagoda neurons were appropriate to the pressure location: in the longitudinal direction the anterior pagoda neuron further away from the pressure sensory neuron had a smaller response with longer latency; inside each ganglion, the anterior pagoda neuron on the contralateral side had a larger response with shorter latency than that on the ipsilateral side. All anterior pagoda neurons excited by pressure sensory neurons comprised a parallel system in which each anterior pagoda neuron was independent from the others. The location information of pressure stimuli was represented through the response of all 40 anterior pagoda neurons covering the whole leech body with a specific pattern of latency and amplitude.     

Activity-dependent induction of facilitation,depression, and post-tetanic potentiation at an insect central synapse

Summary In Manduca sexta larvae, sensory neurons innervating planta hairs on the tips of the prolegs make monosynaptic excitatory connections with motoneurons innervating proleg retractor muscles. Tactile stimulation of the hairs evokes reflex retraction of the proleg. In this study we examined activity-dependent changes in the amplitude of the excitatory postsynaptic potentials (EPSPs) evoked in a proleg motoneuron by stimulation of individual planta hair sensory neurons. Deflection of a planta hair caused a phasic-tonic response in the sensory neuron, with a mean peak instantaneous firing frequency of >300 Hz, and a tonic firing rate of 10–20 Hz. Direct electrical stimulation was used to activate individual sensory neurons to fire at a range of frequencies including those observed during natural stimulation of the hair. At relatively low firing rates (e.g., 1 Hz), EPSP amplitude was stable indefinitely. At higher instantaneous firing frequencies (>10 Hz), EPSPs were initially facilitated, but continuous stimulation led rapidly to synaptic depression. High-frequency activation of a sensory neuron could also produce post-tetanic potentiation, in which EPSP amplitude remained elevated for several min following a stimulus train. Facilitation, depression, and post-tetanic potentiation all appeared to be presynaptic phenomena. These activity-dependent changes in sensory transmission may contribute to the behavioral plasticity of the proleg withdrawal reflex observed in intact insects.Abbreviations ACh acetylcholine - AChE acetylcholine esterase - CNS central nervous system - EPSP excitatory postsynaptic potential - I _h injected hyperpolarizing current - LTP long-term potentiation - PPR principal planta retractor motoneuron - PTP post-tetanic potentiation - R _in input resistance - V _h hyperpolarized potential - V _m membrane potential - VN ventral nerve - VNA anterior branch of the ventral nerve - V _r resting potential.     

Fine-structural characteristics of the antennal sensilla of Agrotis segetum (Insecta: Lepidoptera)

Summary The turnip moth Agrotis segetum possesses seven different types of sensilla: four single-walled (SW), one double-walled (DW), one terminal-pore (TP), and one poreless sensilla (NP).The SW 1 and SW 2 sensilla have the same external appearance, being long and slender, but differ in the branching pattern of the sensory processes: unbranched and branched in SW 1 and SW 2, respectively. The SW 3 sensilla are shorter, sickle-shaped, and contain a large number of branches from the sensory processes. These three sensillar types are innervated by 2–3 sensory cells. The SW 4 sensilla are raisin-shaped and possess three profusely branched sensory processes. The DW sensilla are short and have apical slit-like pores. This sensillar type has 5–6 sensory processes. The TP sensilla possess five sensory processes, one of them terminates basally in a tubular body, the others in the apical part of the long cuticular bristle. The NP sensilla are stout and have apical conelike structures. Two of the sensory processes terminate in the apical part, the third proximally. The third sensory process has a lamellar pattern. The fine structure indicates the following functions: SW and DW sensilla: chemoreception; TP sensillum: chemoreception and mechanoreception; NP sensillum: thermoreception and hygroreception.Supported by joint grants from the Swedish Council for Planning and Coordination of Research, the Swedish Natural Science Research Council, and the Swedish Council for Forestry and Agricultural Research     

Primary sensory neurons containing command neuron peptide constitute a morphologically distinct class of sensory neurons in the terrestrial snail

In the central nervous system of the terrestrial snail Helix, the gene HCS2, which encodes several neuropeptides of the CNP (command neuron peptide) family, is mostly expressed in cells related to withdrawal behavior. In the present work, we demonstrate that a small percentage (0.1%) of the sensory cells, located in the sensory pad and in the surrounding epithelial region ("collar") of the anterior and posterior tentacles, is immunoreactive to antisera raised against the neuropeptides CNP2 and CNP4, encoded by the HCS2 gene. No CNP-like-immunoreactive neurons have been detected among the tentacular ganglionic interneurons. The CNP-like-immunoreactive fiber bundles enter the cerebral ganglia within the nerves of the tentacles (tentacular nerve and medial lip nerve) and innervate the metacerebral lobe, viz., the integrative brain region well-known as the target area for many cerebral ganglia nerves. The procerebral lobe, which is involved in the processing of olfactory information, is not CNP-immunoreactive. Our data suggest that the sensory cells, which contain the CNP neuropeptides, belong to a class of sensory neurons with a specific function, presumably involved in the withdrawal behavior of the snail.     

A catecholaminergic neuron connecting the first two optic neuropiles (Lamina ganglionaris and Medulla externa) of the crayfish Pacifastacus leniusculus

Summary The crustacean optic neuropiles, the lamina ganglionaris and especially the medulla externa, show a specific pattern of green fluorescence with the fluorescence histochemical method of Falck-Hillarp. Normally, only the terminals and the cell bodies fluoresce, but in reserpine-treated animals exogenous catecholamines are taken up by the whole adrenergic neuron and are thus visualized as a whole. Incubating crayfish optic neuropiles in dopamine or -methylnoradrenaline after reserpine treatment demonstrated a tangential neuron connecting the lamina and the medulla externa. The morphology of this tangential neuron differs from the two types of tangential neurons, Tan₁ and Tan₂, previously characterized with Golgi techniques. The catecholaminergic neuron thus constitutes a third tangential neuron type. Acknowledgement. The present study has been supported by the Swedish Natural Science Research Council, grant B 2760-009, the Magnus Bergvall foundation, and the Swedish Medical Research Council, grant 04X-712, the latter to Prof. Bengt Falck to whom we extend our gratitude. We are also indebted to Mrs. Rita Wallén and Miss Maria Walles for their skilled technical assistance. Reserpine (Serpasil^®) was generously given to us by Hässle-Ciba-Geigy AB     

Role of type-specific neuron properties in a spinal cord motor network

Recent recordings from spinal neurons in hatchling frog tadpoles allow their type-specific properties to be defined. Seven main types of neuron involved in the control of swimming have been characterized. To investigate the significance of type-specific properties, we build models of each neuron type and assemble them into a network using known connectivity between: sensory neurons, sensory pathway interneurons, central pattern generator (CPG) interneurons and motoneurons. A single stimulus to a sensory neuron initiates swimming where modelled neuronal and network activity parallels physiological activity. Substitution of firing properties between neuron types shows that those of excitatory CPG interneurons are critical for stable swimming. We suggest that type-specific neuronal properties can reflect the requirements for involvement in one particular network response (like swimming), but may also reflect the need to participate in more than one response (like swimming and slower struggling). Action Editor: Eberhard E. Fetz     

Intrathecally delivered glial cell line-derived neurotrophic factor produces electrically evoked release of somatostatin in the dorsal horn of the spinal cord

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor with an established role in sensory neuron development. More recently it has also been shown to support adult sensory neuron survival and exert a neuroprotective effect on damaged sensory neurons. Some adult small-sized dorsal root ganglion (DRG) cells that are GDNF-sensitive sensory neurons express the inhibitory peptide somatostatin (SOM). Thus, we tested the hypothesis that prolonged GDNF administration would regulate SOM expression in sensory neuron cell bodies in the dorsal root ganglia (DRG) and activity-induced release of SOM from axon terminals in the dorsal horn. Continuous intrathecal delivery of GDNF for 11-13 days significantly increased the number of small DRG cells that expressed SOM. Furthermore, GDNF treatment evoked SOM release in the isolated dorsal horn following electrical stimulation of the dorsal roots that was otherwise undetectable in control rats. Conversely capsaicin-induced release of SOM (EC(50) 50 nM) was not modified by GDNF treatment. These results show that GDNF can regulate central synaptic function in SOM-containing sensory neurons.     

Identification of thermosensory and olfactory neuron-specific genes via expression profiling of single neuron types

Most C. elegans sensory neuron types consist of a single bilateral pair of neurons, and respond to a unique set of sensory stimuli. Although genes required for the development and function of individual sensory neuron types have been identified in forward genetic screens, these approaches are unlikely to identify genes that when mutated result in subtle or pleiotropic phenotypes. Here, we describe a complementary approach to identify sensory neuron type-specific genes via microarray analysis using RNA from sorted AWB olfactory and AFD thermosensory neurons. The expression patterns of subsets of these genes were further verified in vivo. Genes identified by this analysis encode 7-transmembrane receptors, kinases, and nuclear factors including dac-1, which encodes a homolog of the highly conserved Dachshund protein. dac-1 is expressed in a subset of sensory neurons including the AFD neurons and is regulated by the TTX-1 OTX homeodomain protein. On thermal gradients, dac-1 mutants fail to suppress a cryophilic drive but continue to track isotherms at the cultivation temperature, representing the first genetic separation of these AFD-mediated behaviors. Expression profiling of single neuron types provides a rapid, powerful, and unbiased method for identifying neuron-specific genes whose functions can then be investigated in vivo.     

Immunoreactivity of synapses on primary afferent axons and sensory neurons in lamprey spinal cord (<Emphasis Type="Italic">Lampetra fluviatilis</Emphasis>)

The ultrastructure and immunospecificity of synapses on primary afferents and dorsal sensory cells (DCs) were studied in lamprey (Lampetra fluviatilis) spinal cords. Using the postembedding immunogold method with a combination of antibodies—polyclonal antibodies to glutamate and monoclonal antibodies to gamma-aminobutyric acid (GABA)—the presence of GABA-positive on the primary afferent axons and GABA-and glutamate-immunopositive synapses on the DC somatic membranes have been shown. Thus, it is obvious that sensory information in the lamprey is controlled by both presynaptic inhibition via synapses on the primary afferent axons and by direct synaptic influence on the body of the sensory neuron.     

Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation

Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.     

Identified target motor neuron regulates neurite outgrowth and synapse formation of aplysia sensory neurons in vitro

To determine the influence that an appropriate target cell has on the axonal structure of a presynaptic neuron in vivo, we examined the morphologies of individual Aplysia sensory neurons in dissociated cell culture in the presence or absence of identified target motor neurons. We find that an appropriate target, the motor cell L7, regulates the morphological differentiation of the presynaptic sensory neurons in two ways: the target induces the axons of the sensory neurons to develop a more elaborate structure and to form active zones, and the target guides the outgrowth of the sensory neurons. The influence of the appropriate target, L7, on the morphological differentiation of sensory neurons appears to be related to the formation of chemical synaptic connections between the sensory neurons and L7, since sensory neurons co-cultured with an inappropriate target motor neuron do not exhibit a comparable elaboration of their axonal processes.     

The cellular organization and nervous supply of the basilar papilla in the lizard,Calotes versicolor

Summary The basilar papilla of the lizard Calotes versicolor contains about 225 sensory cells. These are of two types: the short-haired type A cells in the ventral (apical) part of the organ, and the type B cells with long hair bundles, in the dorsal (basal) part of the organ. The type A cells are unidirectionally oriented and are covered by a tectorial membrane while the type B cells lack a covering structure and their hair bundles are oriented bidirectionally. Apart from those differences, the type A and type B cells are similar. They are columnar, and display the features common to most sensory cells in inner ear epithelia. The sensory cells are separated by supporting cells, which have long slender processes that keep the sensory cells apart. Close to the surface of the basilar papilla a terminal bar of specialized junctions interlocks adjacent cells. Below this, adjacent supporting cells are linked by an occluding junction.The cochlear nerve enters from the medial (neural) aspect. The fibres of the nerve lose their myelin sheaths as they enter the basilar papilla. Each sensory cell is associated with several nerve endings. All the nerves identified were afferent. Marked variations were seen between nerve endings in the basilar papilla, but no morphological equivalents of any functional differences were observed.This work is supported by grant no. B76-12X-00720-11A from the Swedish Medical Research Council, and by funds from the Karolinska Institute, Stockholm, Sweden.     

The whole-body shortening reflex of the medicinal leech: motor pattern,sensory basis,and interneuronal pathways

The leech whole-body shortening reflex consists of a rapid contraction of the body elicited by a mechanical stimulus to the anterior of the animal. We used a variety of reduced preparations — semi-intact, body wall, and isolated nerve cord — to begin to elucidate the neural basis of this reflex in the medicinal leech Hirudo medicinalis. The motor pattern of the reflex involved an activation of excitatory motor neurons innervating dorsal and ventral longitudinal muscles (dorsal excitors and ventral excitors respectively), as well as the L cell, a motor neuron innervating both dorsal and ventral longitudinal muscles. The sensory input for the reflex was provided primarily by the T (touch) and P (pressure) types of identified mechanosensory neuron. The S cell network, a set of electrically-coupled interneurons which makes up a fast conducting pathway in the leech nerve cord, was active during shortening and accounted for the shortest-latency excitation of the L cells. Other, parallel, interneuronal pathways contributed to shortening as well. The whole-body shortening reflex was shown to be distinct from the previously described local shortening behavior of the leech in its sensory threshold, motor pattern, and (at least partially) in its interneuronal basis.Abbreviations conn connective - DE dorsal excitor motor neuron - DI dorsal inhibitor motor neuron - DP dorsal posterior nerve - DP:B1 dorsal posterior nerve branch 1 - DP:B2 dorsal posterior nerve branch 2 - MG midbody ganglion - VE ventral excitor motor neuron - VI ventral inhibitor motor neuron