Tonic and modulatory subsystems of the complex gravity receptor system in crickets, Gryllus bimaculatus

The gravity receptor system of crickets Gryllus bimaculatus is composed of antennal, cercal and leg subsystems. The cercal gravity receptors are the club-shaped sensilla. Each of these subsystems elicits compensatory head movements during passive roll.The extent of compensatory head movements depends on the strength of the gravitational stimulus applied to the leg subsystem. Amputation of 2 legs never causes a decrease in reflex amplitude. Unilateral amputation of 1 to 3 legs always induces a roll movement of the head to the intact body side. Therefore, the leg gravity receptor system exerts a modulatory and tonic effect on the neck muscles.The gravity receptors of 1 cercus or 1 antenna only elicit compensatory head movements. They exert no tonic effect on the neck muscles.The results are discussed with respect to (i) the proposed connectivity of the cercus-neck muscle pathway, (ii) mutual inhibitory interactions between the sensory pathways originating in the leg gravity receptors, and (iii) the influence of non-gravitationally induced excitation on the occurrence of compensatory head movements during passive roll of the crickets.     

Regulation of neuron cholinoreceptor plasticity of Helix lucorum by second messengers and opioids

The rhythmical local ionophoretic applications of acetylcholine (ACh) to the somatic membrane of Helix lucorum identified neurons evokes the reversible depression of the ACh-induced response which shows cholinoreceptor (ChR) desensitization. ChR desensitization is regulated not by one but by several known second messengers and G-proteins. The endogenous opioids perform the excitation or inhibitory tonic control of the membrane potential in some neurons constantly activating the ionotropic opiate receptors. The direction of neuron ChR desensitization modulation by opioids depends on the type of the activated modulatory opiate receptors (mu or kappa) on the neuron membrane. Second messengers are involved in intracellular mechanism of modulation of the ChR desensitization by opiate kappa-agonist bremazocine.     

Structure and physiology of the locust femoral chordotonal organ

The connective chordotonal organs (COs) in the femora of the prothoracic and mesothoracic legs of the locust Schistocerca gregaria are divided into two parts, the proximal and the distal scoloparia. The proximal scoloparium contains about 150 small neurons and is anchored to the femoral cuticle. The distal scoloparium contains about 50 larger neurons and is connected at its proximal end to both the cuticle and the flexor tibiae muscle.Records were made from the distal scoloparium, classifying units by spike size. The tibial position/total activity response curve is ∪-shaped but when a small number of units is selected the responses occur only when the tibia is on one side of its centre position. The tonic responses display considerable hysteresis and a degree of adaptation which varies with the tibial angle. Units with phasic and phasic-tonic responses are common and their responsiveness depends on the range of angles the tibia is moved through. The same units respond strongly to flexor tibiae contraction with the tibia either fixed or free, and so may serve as receptors for tension in that muscle.The CO mediates phasic resistance reflexes in all three extensor tibiae motoneurons and tonic reflexes in the extensor ‘slow’ neuron. It is suggested that the very detailed information furnished by the CO is used in a complex way in the control of the femoral muscles.     

Neurophysiology of the vibration sense in locusts and bushcrickets: Response characteristics of single receptor units

The response characteristics of the vibration receptors in the legs of the migratory locust, Locusta migratoria, and the tettigoniid Decticus verrucivorus were investigated electro-physiologically by single cell recordings. The legs were stimulated by sinusoidal vibrations. There are four types of vibration receptor in each leg of Locusta and Decticus, which can be classified physiologically. One type—most probably campaniform sensilla—shows a phase-locked response to vibrations from 30 to 200 Hz, its threshold reflecting the displacement. A second type shows similar responses in the same frequency range, but its reactions depend on the stimulus acceleration. The receptor cells of the subgenual organ are very sensitive to vibration from 30 to at least 5000 Hz, and their responses depend on acceleration. There are two types of subgenual receptors, one of which shows a clear maximum of sensitivity between 200 and 1000 Hz, with a threshold below 0.01 m/sec^?2 acceleration. Subgenual receptors with different thresholds and different characteristic frequencies occur in each leg. The receptors of each leg pair have quite similar mean sensitivities and characteristic frequencies. However, in the front legs of tettigoniids the more sensitive subgenual receptors and an additional receptor type also respond to low-frequency airborne sound up to 10 kHz.     

Neurophysiological analysis of locust behaviour during ecdysis: The slow rhythm underlying expansion

The behaviour of Schistocerca during the expansional stage of the imaginal ecdysis was analysed using electromyograms. The behaviour of the abdomen consisted of a slow rhythm in which tonic compressions and rapid ventilation alternated. The same abdominal motor neurones were excited in the tonic compression and rapid expiratory strokes. The results suggest that different interneurones excited the motor neurones in these two phases. The excitation of muscles in the head and thorax was also correlated with the abdominal rhythm.     

Extrasynaptic α6 Subunit-Containing GABAA Receptors Modulate Excitability in Turtle Spinal Motoneurons

Motoneurons are furnished with a vast repertoire of ionotropic and metabotropic receptors as well as ion channels responsible for maintaining the resting membrane potential and involved in the regulation of the mechanisms underlying its membrane excitability and firing properties. Among them, the GABA_A receptors, which respond to GABA binding by allowing the flow of Cl⁻ ions across the membrane, mediate two distinct forms of inhibition in the mature nervous system, phasic and tonic, upon activation of synaptic or extrasynaptic receptors, respectively. In a previous work we showed that furosemide facilitates the monosynaptic reflex without affecting the dorsal root potential. Our data also revealed a tonic inhibition mediated by GABA_A receptors activated in motoneurons by ambient GABA. These data suggested that the high affinity GABA_A extrasynaptic receptors may have an important role in motor control, though the molecular nature of these receptors was not determined. By combining electrophysiological, immunofluorescence and molecular biology techniques with pharmacological tools here we show that GABA_A receptors containing the α₆ subunit are expressed in adult turtle spinal motoneurons and can function as extrasynaptic receptors responsible for tonic inhibition. These results expand our understanding of the role of GABA_A receptors in motoneuron tonic inhibition.     

Functional role of leg receptors of the cockroach Periplaneta americana in the system of walking control

This work deals with study of role of the hairplate and of campaniform sensillae (CS) on legs of the cockroach Periplaneta americana in the system of walking control. Three receptors were shown to induce their regulatory, correctional effect on the rhythm of the cockroach steps depending on the external circumstances. These effects are mainly realized only at slow walking.     

Intracellular transmission of the cholinergic signal in the chick amnion

The role of the system of deposited calcium in the mediation of contractile reactions to carbachol in an isolated amnion of 11–13 day old chicken embryo was studied. It was found that thapsigargin (2 μM, 20 min), an inhibitor of the endoplasmic reticulum Ca²⁺-ATPases, decreases the tonic reaction to carbachol by 40 ± 2%. In the presence of U73122 (5–10 μM, 10 min), a phosphoinositide-specific phospholipase C inhibitor, the rhythmic contractile reaction of the amnion to carbachol is blocked, whereas the tonic reaction decreases to 47 ± 9% of the initial one. Ryanodine (10 μM, 5 min) inhibits the spontaneous contractile activity of the amnion and decreases the tonic reaction to carbachol to 36 ± 3% relative to control. In the presense of ryanodine, nifedipine (0.05 μM) completely blocks the tonic reaction to carbachol. Thus, calcium mobilized from intracellular stores via inositol trisphosphate and ryanodine receptors is involved in realization of contractile reactions, mediated by M3 receptors, in the chick amnion.     

Tonic inhibition in spinal ventral horn interneurons mediated by α5 subunit-containing GABA(A) receptors

GABA_A receptors mediate synaptic and tonic inhibition in many neurons of the central nervous system. These receptors can be constructed from a range of different subunits deriving from seven identified families. Among these subunits, α₅ has been shown to mediate GABAergic tonic inhibitory currents in neurons from supraspinal nuclei. Likewise, immunohistochemical and in situ hybridization studies have shown the presence of the α₅ subunit in spinal cord neurons, though almost nothing is known about its function. In the present report, using slices of the adult turtle spinal cord as a model system we have recorded a tonic inhibitory current in ventral horn interneurons (VHIs) and determined the functional contribution of the α₅ subunit-containing GABA_A receptors to this current. Patch clamp studies show that the GABAergic tonic inhibitory current in VHIs is not affected by the application of antagonists of the α_4/6 subunit-containing GABA_A receptors, but is sensitive to L-655708, an antagonist of the GABA_A receptors containing α₅ subunits. Last, by using RT-PCR and immunohistochemistry we confirmed the expression of the α₅ subunit in the turtle spinal cord. Together, these results suggest that GABA_A receptors containing the α₅ subunit mediate the tonic inhibitory currents observed in VHIs.     

T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression

Signal transduction pathways guided by cellular receptors commonly exhibit low-level constitutive signaling in a continuous, ligand-independent manner. The dynamic equilibrium of positive and negative regulators establishes such a tonic signal. Ligand-independent signaling by the precursors of mature antigen receptors regulates development of B and T lymphocytes. Here we describe a basal signal that controls gene expression profiles in the Jurkat T cell line and mouse thymocytes. Using DNA microarrays and Northern blots to analyze unstimulated cells, we demonstrate that expression of a cluster of genes, including RAG-1 and RAG-2, is repressed by constitutive signals requiring the adapter molecules LAT and SLP-76. This TCR-like pathway results in constitutive low-level activity of Erk and Abl kinases. Inhibition of Abl by the drug STI-571 or inhibition of signaling events upstream of Erk increases RAG-1 expression. Our data suggest that physiologic gene expression programs depend upon tonic activity of signaling pathways independent of receptor ligation.     

Sense organs in the femur of the stick insect and their relevance to the control of position of the femur-tibia-joint

Summary The sensory innervation pattern is described for the femur of the middle and the hind legs ofCarausius morosus. — In one of the nerves (F121) extracellular recordings show a unit which mirrors the tension of the flexor tibiae muscle (tension receptor). The tension receptor increases the firing rate of the slow extensor tibiae motoneuron. It measures the tension of one or more muscle fibres of the anterior side near the distal end of the muscle. The anatomical basis of this receptor is uncertain. — Another receptor was found on the ventral side of the distal end of the apodeme of the extensor tibiae muscle (apodeme receptor). Recordings from this receptor could not be obtained inCarausius. But inExtatosoma tiaratum it responded to stretching of the nerve. In the natural position it shows a minimum of excitation in the 90°-position of the femur-tibia-joint and an increase in firing rate for both flexion and extension. — Tactile hairs react phasically and have no special sensitivity for one direction. Two receptors at the dorsal side of the femur-tibia-joint (RDAL and RDPL), which are situated in the same position as inSchistocerca hind legs, react phasically to extension movements and fire tonically in the most extended position of the joint. — The influence of these receptors on the position of the femur-tibia-joint is only weak.Supported by Deutsche Forschungsgemeinschaft     

Effect of the background activity of a network of excitatory neuron-like elements on the conduction of excitation

Calculation on a mathematical model showed that for distortion-free conduction of excitation through a net of excitatory elements (EEs) a system is necessary of optimum correlation of EEs parameters, links between them and of external influences. When these parameters are deviated from their optimum values, excitation is conducted through the net either with attenuation or with intensification (as a result of divergence and convergence of the influences of the previous layer on the following one). The background activity which is above threshold of impulse activity emergence and which is created by common effects on all EEs, prevents the revealing of the input EEs activation at the net output. Near-threshold tonic net activation facilitates excitation conduction through it. Periodic net activity facilitates excitation conduction through it only under optimum correlation of its parameters and the time of its conduction through the net. At disturbance of this condition, excitation conduction through the net is limited.     

Endogenous 5-HT2B receptor activation regulates neonatal respiratory activity in vitro

An implication of 5-HT(2B) receptors in central nervous system has not yet been clearly elucidated. We studied the role of different 5-HT(2) receptor subtypes in the medullary breathing center, the pre-B?tzinger complex, and on hypoglossal motoneurons in rhythmically active transversal slice preparations of neonatal rats and mice. Local microinjection of 5-HT(2) receptor agonists revealed tonic excitation of hypoglossal motoneurons. Excitatory effects of the 5-HT(2B) receptor agonist BW723C86 could be blocked by bath application of LY272015, a highly selective 5-HT(2B) receptor antagonist. Excitatory effects of the 5-HT(2A/B/C) receptor agonist alpha-methyl 5-HT could be blocked by the preferential 5-HT(2A) receptor antagonist ketanserin. Therefore, 5-HT-induced excitation of hypoglossal motoneurons is mediated by convergent activation of 5-HT(2A) and 5-HT(2B) receptors. Local microinjection of BW723C86 in the pre-B?tzinger complex increased respiratory frequency. Bath application of LY272015 blocked respiratory activity, whereas ketanserin had no effect. Therefore, endogenous 5-HT appears to support tonic action on respiratory rhythm generation via 5-HT(2B) receptors. In preparations of 5-HT(2B) receptor-deficient mice, respiratory activity appeared unaltered. Whereas BW723C86 and LY272015 had no effects, bath application of ketanserin disturbed and blocked rhythmic activity. This demonstrates a stimulatory role of endogenous 5-HT(2B) receptor activation at the pre-B?tzinger complex and hypoglossal motoneurons that can be taken up by 5-HT(2A) receptors in the absence of 5-HT(2B) receptors. The presence of functional 5-HT(2B) receptors in the neonatal medullary breathing center indicates a potential convergent regulatory role of 5-HT(2B) and -(2A) receptors on the central respiratory network.     

Pharmacological analysis of the activation and receptor properties of the tonic GABA(C)R current in retinal bipolar cell terminals

GABAergic inhibition in the central nervous system (CNS) can occur via rapid, transient postsynaptic currents and via a tonic increase in membrane conductance, mediated by synaptic and extrasynaptic GABA(A) receptors (GABA(A)Rs) respectively. Retinal bipolar cells (BCs) exhibit a tonic current mediated by GABA(C)Rs in their axon terminal, in addition to synaptic GABA(A)R and GABA(C)R currents, which strongly regulate BC output. The tonic GABA(C)R current in BC terminals (BCTs) is not dependent on vesicular GABA release, but properties such as the alternative source of GABA and the identity of the GABA(C)Rs remain unknown. Following a recent report that tonic GABA release from cerebellar glial cells is mediated by Bestrophin 1 anion channels, we have investigated their role in non-vesicular GABA release in the retina. Using patch-clamp recordings from BCTs in goldfish retinal slices, we find that the tonic GABA(C)R current is not reduced by the anion channel inhibitors NPPB or flufenamic acid but is reduced by DIDS, which decreases the tonic current without directly affecting GABA(C)Rs. All three drugs also exhibit non-specific effects including inhibition of GABA transporters. GABA(C)R ρ subunits can form homomeric and heteromeric receptors that differ in their properties, but BC GABA(C)Rs are thought to be ρ1-ρ2 heteromers. To investigate whether GABA(C)Rs mediating tonic and synaptic currents may differ in their subunit composition, as is the case for GABA(A)Rs, we have examined the effects of two antagonists that show partial ρ subunit selectivity: picrotoxin and cyclothiazide. Tonic and synaptic GABA(C)R currents were differentially affected by both drugs, suggesting that a population of homomeric ρ1 receptors contributes to the tonic current. These results extend our understanding of the multiple forms of GABAergic inhibition that exist in the CNS and contribute to visual signal processing in the retina.     

Involvement of GABA and cholinergic receptors in the nucleus accumbens on feedback control of somatodendritic dopamine release in the ventral tegmental area

The objectives of the present study were to examine the involvement of GABA and cholinergic receptors within the nucleus accumbens (ACB) on feedback regulation of somatodendritic dopamine (DA) release in the ventral tegmental area (VTA). Adult male Wistar rats were implanted with ipsilateral dual guide cannulae for in vivo microdialysis studies. Activation of the feedback system was accomplished by perfusion of the ACB with the DA uptake inhibitor GBR 12909 (GBR; 100 microm). To assess the involvement of GABA and cholinergic receptors in regulating this feedback system, antagonists (100 microm) for GABAA (bicuculline, BIC), GABAB (phaclofen, PHAC), muscarinic (scopolamine, SCOP), and nicotinic (mecamylamine, MEC) receptors were perfused through the probe in the ACB while measuring extracellular DA levels in the ACB and VTA. Local perfusion of the ACB with GBR significantly increased (500% of baseline) the extracellular levels of DA in the ACB and produced a concomitant decrease (50% of baseline) in the extracellular DA levels in the VTA. Perfusion of the ACB with BIC or PHAC alone produced a 200-400% increase in the extracellular levels of DA in the ACB but neither antagonist altered the levels of DA in the VTA. Co-perfusion of either GABA receptor antagonist with GBR further increased the extracellular levels of DA in the ACB to 700-800% of baseline. However, coperfusion with BIC completely prevented the reduction in the extracellular levels of DA in the VTA produced by GBR alone, whereas PHAC partially prevented the reduction. Local perfusion of the ACB with either MEC or SCOP alone had little effect on the extracellular levels of DA in the ACB or VTA. Co-perfusion of either cholinergic receptor antagonist with GBR markedly reduced the extracellular levels of DA in the ACB and prevented the effects of GBR on reducing DA levels in the VTA. Overall, the results of this study suggest that terminal DA release in the ACB is under tonic GABA inhibition mediated by GABAA (and possibly GABAB) receptors, and tonic cholinergic excitation mediated by both muscarinic and nicotinic receptors. Activation of GABAA (and possibly GABAB) receptors within the ACB may be involved in the feedback inhibition of VTA DA neurons. Cholinergic interneurons may influence the negative feedback system by regulating terminal DA release within the ACB.     

Influence of respiratory network drive on phrenic motor output evoked by activation of cat pre-Botzinger complex

We have previously demonstrated that microinjection of dl-homocysteic acid (DLH), a glutamate analog, into the pre-B?tzinger complex (pre-B?tC) can produce either phasic or tonic excitation of phrenic nerve discharge during hyperoxic normocapnia. Breathing, however, is influenced by input from both central and peripheral chemoreceptor activation. This influence of increased respiratory network drive on pre-B?tC-induced modulation of phrenic motor output is unclear. Therefore, these experiments were designed to examine the effects of chemical stimulation of neurons (DLH; 10 mM; 10-20 nl) in the pre-B?tC during hyperoxic modulation of CO2 (i.e., hypercapnia and hypocapnia) and during normocapnic hypoxia in chloralose-anesthetized, vagotomized, mechanically ventilated cats. For these experiments, sites were selected in which unilateral microinjection of DLH into the pre-B?tC during baseline conditions of hyperoxic normocapnia [arterial PCO2 (PaCO2) = 37-43 mmHg; n = 22] produced a tonic (nonphasic) excitation of phrenic nerve discharge. During hypercapnia (PaCO2 = 59.7 +/- 2.8 mmHg; n = 17), similar microinjection produced excitation in which phasic respiratory bursts were superimposed on varying levels of tonic discharge. These DLH-induced phasic respiratory bursts had an increased frequency compared with the preinjection baseline frequency (P < 0.01). In contrast, during hypocapnia (PaCO2 = 29.4 +/- 1.5 mmHg; n = 11), microinjection of DLH produced nonphasic tonic excitation of phrenic nerve discharge that was less robust than the initial (normocapnic) response (i.e., decreased amplitude). During normocapnic hypoxia (PaCO2 = 38.5 +/- 3.7; arterial Po2 = 38.4 +/- 4.4; n = 8) microinjection of DLH produced phrenic excitation similar to that seen during hypercapnia (i.e., increased frequency of phasic respiratory bursts superimposed on tonic discharge). These findings demonstrate that phrenic motor activity evoked by chemical stimulation of the pre-B?tC is influenced by and integrates with modulation of respiratory network drive mediated by input from central and peripheral chemoreceptors.     

An analysis of the 5-hydroxytryptamine (serotonin) receptor subtypes of central neurones of Helix aspersa

1. Intracellular recordings were made from identified neurones in the central nervous system of Helix aspersa. Two types of cell were used, those excited by 5-hydroxytryptamine (5-HT) and acetylcholine and those inhibited by 5-HT and dopamine. The actions of a range of 5-HT agonists and antagonists were tested for their ability to interact with 5-HT receptors.2. 5-Carboxyamidotryptamine, α-methyl-5-HT and N-methyl-5-HT were active on cells excited by 5-HT, with similar potencies to 5-HT. Only 5-carboxyamidotryptamine and 5-methoxytryptamine were equiactive with 5-HT on cells inhibited by 5-HT. Most of the non-indole analogues were inactive or very weak agonists on both receptors.3. MDL 72222 was the most active antagonist tested against 5-HT excitation, showing some selectivity for 5-HT over acetylcholine. Cinanserin and ketanserin also showed selectivity for 5-HT over acetylcholine.4. Tryptamine was inhibitory on both cell types and was a potent antagonist of 5-HT excitation, showing selectivity for 5-HT over acetylcholine.5. It is concluded that the 5-HT excitatory receptor recognizes the indole nucleus with substitution on position 5, save for 5-fluorotryptamine which was inhibitory. It does not appear that these 5-HT receptors can be classified in terms of the vertebrate subtypes of 5-HT receptor. However, it should be noted that only two receptor subtypes located on a small number of neurones were studied in these experiments and other 5-HT receptor subtypes may be located on other groups of neurones and peripheral tissues. These receptors may recognize other 5-HT receptor ligands including non-indoles.     

The bimodal auditory-vibratory system of the thoracic ventral nerve cord in Locusta migratoria (Acrididae, Locustinae, Oedipodini).

In locusts the auditory receptors of the tympanal organs and many of the vibratory receptors of all 6 legs converge at the level of the thoracic ventral nerve cord, forming a combined auditory-vibratory sensory system; it is represented by the VS-, S-, and V-neurons ascending to the supraesophageal ganglion. The connections between vibratory receptors of the different legs and the dendritic inputs of the bimodal ascending neurons are investigated in this report. As an example, the dendritic branches of the G- and V3-neurons for auditory and vibratory input could be localized by simultaneous recording at 2 different positions of the axon. The vibratory input from the receptors of the different legs was determined. Segmental and/or intersegmental thoracic interneurons are intercalated between the receptors and the ascending auditory-vibratory neurons (G- and V3-neurons). The morphology and function of 2 intersegmental vibratory interneurons (VI1- and VI2-neurons) are described. They probably connect the vibratory receptors of 1 (or 2) leg(s) of 1 thoracic segment with the different bimodal auditory-vibratory neurons. The importance of the anterior Ring Tract for synaptic connection between receptor cells, first order interneurons, and bimodal auditory-vibratory neurons is discussed on the basis of morphological and physiological data.