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SOME ACTIONS OF CENTRALLY ACTIVE AND OTHER DRUGS ON THE TRANSMISSION OF SINGLE NERVE IMPULSES THROUGH THE ISOLATED SUPERIOR CERVICAL GANGLION PREPARATION OF THE RABBIT.

The effect of some centrally-active and other drugs on the transmission of single nerve impulses through the isolated superior cervical ganglion preparation of the rabbit has been studied by recording both preganglionic and postganglionic action potentials. Block of conduction in the axon could be distinguished from block of the synaptic mechanism. The drugs did not appear to exert any one characteristic form of blocking action. A continuous spectrum of drug action linked an agent such as meprobamate which acted predominantly on the synapse to benactyzine which acted mainly by blocking axonal conduction. The drugs have been divided into three groups. Group I: hexamethonium, meprobamate, paraldehyde, amylobarbitone, methylpentynol and azacyclonal; these acted relatively selectively at the ganglion. Group II: N714C (the cis-isomer of chlorprothixene), prochlorperazine, methylpentynol carbamate, pipradrol, promethazine, perphenazine and procaine; the action of these drugs on the ganglion could be accounted for entirely in terms of their axonal depressant action. Group III: chlorprothixene, promazine, N720 (dihydrochlorprothixene), chlorpromazine, hydroxyzine and benactyzine; these drugs also blocked axonal conduction but in addition they appeared to exert a "facilitating" action at the ganglionic synapse. The actions of adrenaline, adrenochrome, iproniazid, ergotoxine, mescaline and lysergic acid diethylamide on transmission were also studied. The implications of the modifications of ganglionic transmission produced by these drugs is discussed.

Action Potentials↗

Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody.

BACKGROUND: The clinical characteristics of autoimmune autonomic neuropathy are only partially defined. More than 50% of patients with high levels of ganglionic acetylcholine receptor (AChR) autoantibodies have a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal tract symptoms, and neurogenic bladder. OBJECTIVE: To compare patients with idiopathic autonomic neuropathy who were seropositive (n = 19) and seronegative (n = 87) for ganglionic AChR antibodies. DESIGN: Retrospective review of autonomic programmatic database. SETTING: Autonomic Disorders Program Project at Mayo Clinic College of Medicine, Rochester, Minn. PATIENTS: We evaluated a cohort of 87 patients with idiopathic autonomic neuropathy who had undergone full autonomic testing and neurological evaluation and who had a complete panel of paraneoplastic and ganglionic AChR antibodies. We compared patients seropositive (n = 19) and seronegative (n = 87) for ganglionic AChR antibodies. RESULTS: The seropositive group had a significant overrepresentation of abnormal pupillary responses (12/18 [67%] vs 12/87 [14%]; P<.001), sicca complex (9/15 [60%] vs 11/47 [23%]; P =.01), and lower gastrointestinal tract dysautonomia (16/19 [84%] vs 48/85 [56%]; P =.02). A subacute mode of onset was more common in the seropositive group (12/19 [63%] vs 23/84 [27%]; P =.004). Results of quantitative autonomic function tests differed significantly in the 2 groups only in the cardiovagal domain. Because subacute onset was overrepresented in the seropositive group, we analyzed the data separately, controlling for temporal profile (ie, the relationship between antibody status and symptoms while controlling for rate of onset). The relationships between antibody status and clinical profile (eg, presence of sicca complex, pupillary abnormalities, and lower gastrointestinal tract symptoms) generally remained significant regardless of onset rate, indicating that the associations are not due to temporal profile. CONCLUSIONS: These observations support the concept that ganglionic AChR antibodies are diagnostically and pathophysiologically important. Patients with orthostatic hypotension and prominent cholinergic dysautonomia are most likely to be seropositive for ganglionic AChR antibody.

Autoantibodies↗

Comparison of photoreceptor spatial density and ganglion cell morphology in the retina of human, macaque monkey, cat, and the marmoset Callithrix jacchus.

We studied the relationship between the morphology of ganglion cells and the spatial density of photoreceptors in the retina of two Old World primates, human and macaque monkey; the diurnal New World marmoset Callithrix jacchus; and the cat. Ganglion cells in macaque and marmoset were labelled by intracellular injection with Neurobiotin or by DiI diffusion labelling in fixed tissue. Cone photoreceptor densities were measured from the same retinas. Supplemental data for macaque and data for human and cat were taken from published studies. For the primates studied, the central retina is characterised by a constant numerical convergence of cones to ganglion cells. Midget ganglion cells derive their input, via a midget bipolar cell, from a single cone. Parasol cells derive their input from 40-140 cones. Outside the central retina, the convergence increases with eccentricity. The convergence to beta cells in the cat retina is very close to that for parasol cells in primate retina. The convergence of rod photoreceptors to ganglion cells is similar in human, macaque, and marmoset, with parasol cells receiving input from 10-15 times more rods than midget cells. The low convergence of cones to midget cells in human and macaque retinas is associated with distinctive dendritic "clusters" in midget cells' dendritic fields. Convergence in marmoset is higher, and the clusters are absent. We conclude that the complementary changes in photoreceptor density and ganglion cell morphology should be considered when forming linking hypotheses between dendritic field, receptive field, and psychophysical properties of primate vision.

Animals↗

Nerve pathways between the pterygopalatine ganglion and eye in cats.

By dissection of thiocholine-stained orbital preparations, it has been determined that three different nerve pathways link the pterygopalatine ganglion and the eye in cats. 1) Nerves from the proximal half of the ganglion join a plexus of nerves and ganglion cells in the rete mirabile of the maxillary artery. Branches of the internal carotid nerve also supply this plexus. Fine nerves from the plexus travel to the optic nerve and then to the eye, accompanying both the nasociliary nerve that passes through the rete and the ciliary arteries that arise from the rete. 2) One or more nerves from the nerve of the pterygoid canal and from a prominent accessory ganglion near the orbital apex course to the inferior optic nerve surface at the optic foramen; these then run distally along the optic nerve to fuse with ciliary nerves or to accompany ciliary arteries entering the eye. 3) Other nerves from the pterygopalatine ganglion travel medially around the extraocular muscle cone to join the ethmoidal and infratrochlear branches of the nasociliary nerve; some nerves from the ganglion then take a retrograde course to the optic nerve, where they join ciliary nerves or arteries to the eye. All three pathways may transmit sympathetic, parasympathetic and somatic sensory nerve fibers.

Animals↗

Pathways of anesthetic from the thoracic paravertebral region to the celiac ganglion.

Communication between the lower thoracic paravertebral region and the celiac ganglion through the retrocrural space was investigated. After dye was injected into the endothoracic fascia in the lower thoracic paravertebral region at the T11 level, its spread to the celiac ganglion was examined in fifteen cadavers. The dye reached the celiac ganglion in nine cadavers (60%) by passing through the retrocrural space, along the greater and lesser splanchnic nerves and through the split in the crus of the diaphragm through which the splanchnic nerves traveled. In the remaining six cadavers, dye spread toward the ganglion along the crus of the diaphragm. In three living subjects the spread of a radio-opaque dye injected in the same manner was studied using 3D-computed tomography. This study confirmed that the radio-opaque dye traveled toward the celiac ganglion along the crus of the diaphragm. From our results we suggest that a fluid communication may exist between the lower thoracic paravertebral region and the celiac ganglion in cadavers and in living humans and that clinicians should be aware of this possible route of spread when administering lower thoracic paravertebral anesthesia.

Adult↗

Displaced ganglion cells and the accessory optic system of pigeon.

The central projection and retinal distribution of displace ganglion cells (DGC's) are described for the pigeon. Discrete, localized injections of horseradish peroxidase (HRP) into the nucleus of the basal optic root (nBOR) complex labeled as many as 4,800 DGC's in the contralateral retina. The greatest densities of DGC's were observed in the more peripheral regions of the middle and inferior temporal regions of the retina, with lowest densities occurring in the inferior nasal, red field, and foveal areas. Large HRP injections of the tectal lobes, which did not include the pretectal, accessory optic (nBOR), hypothalamic, or thalamic visual nuclei, labeled only ganglion cells within the ganglion cells layer. An HRP injection centered within the nucleus lentiformis mesencephali, also including portions of the optic tectum and optic tract, labeled only ganglion cells within the ganglion cell layer of the contralateral retina. DGC's thus appear to be the primary, if not exclusive, source of retinal afferents to the nBOR complex in pigeon. The observed retinal distribution of DGC's indicates that the areas of retina with the greatest density of cells in the receptor layer, inner nuclear layer, and ganglion cell layer are relatively devoid of DGC's. Since the nBOR complex projects directly upon the vestibulocerebellum and oculomotor nuclei, DGC's would thus appear to be involved in neural circuits that mediate oculomotor reflexes and visuomotor behavior.

Animals↗

Morphology of intracellularly labeled canine intracardiac ganglion cells.

The purpose of this study was to determine the morphological organization and structure-function correlation of mammalian intracardiac ganglion cells. Conventional intracellular microelectrode techniques were applied to the tissue whole mount preparation of canine intracardiac ganglia. Forty neurons were intracellularly recorded and labeled by means of horseradish peroxidase iontophoresis. Cell morphology was quantitatively analyzed by light microscopy and camera lucida technique. Somata were elongated (mean 62 x 40 microns) and had 2-12 primary dendrites restricted within the ganglion. Almost half of the neurons had either a short axon that was traced only within the ganglion or no axon distinguishable. These neurons may have perhaps been intraganglionically active neurons. The other cells had a long axon that either coursed out of the ganglion to peripheral cardiac tissue or exited the ganglion via interganglionic nerve to innervate more remote cardiac tissue or cells in other intracardiac ganglia. Interaction between neurons was suggested by the close proximity of processes from different neurons. Previously defined electrophysiological cell types (R-, S-, and N-cells), which were significantly different in their passive and active membrane properties, had different morphological features of the somata but not the axonal or dendritic processes. Intraganglionic or long axon neurons were not associated with a particular electrophysiological cell type. These findings provide the possibility of ganglionic modulation of vagal efferent activity in mammalian heart and also provide some morphological basis for the electrophysiological cell types.

Animals↗

The abdominal ganglion of Aplysia brasiliana: a comparative morphological and electrophysiological study, with notes on A. dactylomela.

The ultrastructure and electrophysiological properties of neurons in the abdominal (visceral) ganglion of the marine opisthobranch gastropod Aplysia brasiliana have been investigated to determine whether this preparation compares favorably with the well studied A. californica for neurobiological research. In general, the topography, morphology and physiological characteristics, including synaptic connections, of neurons in this ganglion are quite similar to those of A. californica. There is close correspondence between the two animals in terms of each of the identified cells or neuronal clusters in the ganglion, including the presence of the cell L10 (interneuron I) in A. brasiliana which makes synaptic connections comparable with those in A. californica. New follower cells of this interneuron have been found in A. brasiliana. This species offers some advantages in that the connective tissue surrounding the ganglion is thinner and more transparent, making cell identification and penetration easier. A. brasiliana appears to exhibit the behaviors of A. californica that have been used in previous functional analyses of neural circuits. In addition, this species swims and exhibits a "burrowing" activity less commonly seen in A. californica. The rich repertoire of behaviors and accessibility of large identifiable and functionally interconnected neurons makes this species of Aplysia an excellent model preparation for future neurobiological studies. Similar, less thorough, investigations of the abdominal ganglion of A. dactylomela indicate that this species is also very similar to A. californica in terms of the identified cells in the abdominal ganglion.

Animals↗

The caudal ganglion of the leech, with particular reference to homologues of segmental touch receptors.

The caudal ganglion of the leech, which provides sensory and motor innervation to the posterior sucker, represents the fusion of seven embryonic segmental ganglia. Although fused, each of the seven contributing ganglia ("subganglia") of the caudal ganglion can be distinguished morphologically and functionally. The roots from each subganglion carry the axons of mechanoreceptors homologous to "touch" cells found in the segmental ganglia and the subesophageal compound ganglion. The receptive fields supplied by the touch cells of the caudal ganglion are uniquely arranged and reveal the modified segmentation of the circular posterior sucker. Extensive overlap of sensory innervation occurs between adjacent segments of the sucker, beyond the overlap characteristic of the homologous cells of body segments. It thus appears that the touch receptors of the caudal ganglion are less restricted than receptors of the segmental ganglia with regard to their territories of innervation. The caudal ganglion has additional unique properties that establish it as a distinct integrative center of the leech CNS.

Animals↗

Nicotinic acetylcholine receptor mRNA in dorsal root ganglion neurons.

Nicotinic acetylcholine receptor (AChR) genes are expressed in subpopulations of chick dorsal root ganglion (DRG) neurons. In 18-day embryonic ganglia, 19% of the neurons have material homologous to neuronal AChR alpha 3 gene mRNA, and 8% have material homologous to alpha 4 mRNA as seen with in situ hybridization. RNAase protection experiments confirm that DRG RNA contains alpha 3 and alpha 4 transcripts, and Northern blot analysis establishes the size of the transcripts as being 3.5 and 3.3 kb, respectively. The proportion of DRG neurons containing alpha 3 mRNA does not decline up through 1 year post-hatch, indicating that alpha 3 gene expression is not a developmentally transient event in the ganglion. An antiAChR monoclonal antibody detects cross-reacting material in 16% of the DRG neurons from 18-day embryos, indicating that AChR mRNA is translated into protein. Electrophysiological measurements confirm the presence of functional AChRs on DRG neurons freshly isolated from 18-day embryos: 24% of the neurons have substantial ACh sensitivities, whereas another 23% have small but detectable responses. Staining dorsal root ganglion sections with an anticholine acetyltransferase antiserum reveals cross-reactive material localized in axons in the ganglion; no evidence suggests the presence of cholinergic synaptic structures or AChR clusters on neuronal somata in the ganglion. It is possible that AChRs on DRG neurons participate in a diffuse form of transmission between the cholinergic fibers and a subpopulation of neuronal somata in the ganglion. Alternatively, AChRs on the somata may represent an ectopic distribution of receptors whose primary function is at the terminals of central or peripheral DRG processes.

Acetylcholine↗

Neuronal differentiation from postmitotic precursors in the ciliary ganglion.

In the chick ciliary ganglion, neuronal number is kept constant between St. 29 and St. 34 (E6-E8) despite a large amount of cell death. Here, we characterize the source of neurogenic cells in the ganglion as undifferentiated neural crest-derived cells. At St. 29, neurons and nonneuronal cells in the ciliary ganglion expressed the neural crest markers HNK-1 and p75(NTR). Over 50% of the cells were neurons at St. 29; of the nonneuronal cells, a small population expressed glial markers, whereas the majority was undifferentiated. When placed in culture, nonneuronal cells acquired immunoreactivity for HuD, suggesting that they had commenced neuronal differentiation. The newly differentiated neurons arose from precursors that did not incorporate bromodeoxyuridine. To test whether these precursors could undergo neural differentiation in vivo, purified nonneuronal cells from St. 29 quail ganglia were transplanted into chick embryos at St. 9-14. Subsequently, quail cells expressing neuronal markers were found in the chick ciliary ganglion. The existence of this precursor pool was transient because nonneuronal cells isolated from St. 38 ganglia failed to form neurons. Since all ciliary ganglion neurons are born prior to St. 29, these results demonstrate that there are postmitotic neural crest-derived precursors in the developing ciliary ganglion that can differentiate into neurons in the appropriate environment.

Animals↗

Morphology and location of dense-core vesicles in the stomatogastric ganglion of the lobster, Panulirus interruptus.

The appearance and distribution of dense-core vesicles in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, were examined using transmission electron microscopy. Following five fixation techniques, three types of dense-core vesicles were identified on the basis of size and morphology. Type-I vesicles are found in a distinct neuronal fiber system that appears to be involved in chemical transmission within the ganglion. Type-II vesicles occur in nerve processes in the ganglion, in major nerve trunks and in the perineural sheath of the nerves and ganglion. Type-III vesicles are present in all neuronal somata of the ganglion. The distinct morphology and location of the three types of vesicles suggest that their functional roles differ. Furthermore, the histochemical, biochemical and physiological data available for the stomatogastric ganglion indicate that Type-I vesicles may store dopamine.

Animals↗

Serotonin-immunoreactive neurons in the median protocerebrum and suboesophageal ganglion of the sphinx moth Manduca sexta.

Serotonin-immunoreactive neurons in the median protocerebrum and suboesophageal ganglion of the sphinx moth Manduca sexta were individually reconstructed. Serotonin immunoreactivity was detected in 19-20 bilaterally symmetrical pairs of interneurons in the midbrain and 10 pairs in the suboesophageal ganglion. These neurons were also immunoreactive with antisera against DOPA decarboxylase. All major neuropil regions except the protocerebral bridge are innervated by these neurons. In addition, efferent cells are serotonin-immunoreactive in the frontal ganglion (5 neurons) and the suboesophageal ganglion (2 pairs of neurons). The latter cells probably give rise to an extensive network of immunoreactive terminals on the surface of the suboesophageal ganglion and suboesophageal nerves. Most of the serotonin-immunoreactive neurons show a gradient in the intensity of immunoreactive staining, suggesting low levels of serotonin in cell bodies and dendritic arbors and highest concentrations in axonal terminals. Serotonin-immunoreactive cells often occur in pairs with similar morphological features. With one exception, all serotonin-immunoreactive neurons have bilateral projections with at least some arborizations in identical neuropil areas in both hemispheres. The morphology of several neurons suggests that they are part of neuronal feedback circuits. The similarity in the arborization patterns of serotonin-immunoreactive neurons raises the possibility that their outgrowing neurites experienced similar forces during embryonic development. The morphological similarities further suggest that serotonin-immunoreactive interneurons in the midbrain and suboesophageal ganglion share physiological characteristics.

Animals↗

Receptive field mechanisms of sustained and transient retinal ganglion cells in the cat.

Receptive field organization of 135 sustained and 45 transient retinal ganglion cells was investigated in lightly pentobarbitone-anaesthetised cats. Stimuli were concentric annuli presented alone or simultaneously with a small spot centred on the receptive field, against photopic, mesopic or scotopic backgrounds. The addition of the test spot led to reduction in diameter of the centre-surround boundary of receptive fields of sustained retinal ganglion cells (assessed with annuli), and a decrease in diameter of the annulus which was most effective on the surround. In transient cells there was only marginal reduction in diameter of the centre-surround boundary, measured with annuli, and little or no decrease in diameter of the most effective annulus. Reducing background intensity from photopic to scotopic induced changes in response patterns and receptive field organization of sustained and transient retinal ganglion cells which were independent of stimulus intensity. Against photopic backgrounds, large annuli evoked surround-type responses from the majority of transient ganglion cells and from all sustained cells. In the scotopic range, surround-type responses could still be evoked from sustained cells, whereas predominantly centre-type responses were obtained throughout the receptive fields of transient cells. With transition from cone to rod vision, receptive field surrounds of sustained and transient cells became progressively less responsive than centres; in consequence the diameter of the centre-surround boundary increased. The initial, high frequency burst of impulses in discharges at annulus onset or offset became less evident and response latency increased substantially. The results are consistent with a model in which the centre and surround receptive field mechanisms are spatially co-extensive in transient retinal ganglion cells, albeit of different shape, but only partially overlapping in sustained retinal ganglion cells. It is suggested that the surround mechanism in sustained cells is spatially more extensive than the centre mechanism but does not extend entirely through the centre of the field.

Animals↗

Structures with GABA-like and GAD-like immunoreactivity in the cervical sympathetic ganglion complex of adult rats.

The distribution of gamma-aminobutyric acid (GABA)-like and glutamate decarboxylase (GAD)-like immunoreactivity was studied in the cervical sympathetic ganglion complex of rats, including the intermediate and inferior cervical ganglia and the uppermost thoracic ganglion. GABA-positive axons may enter the ganglion complex via its caudal end. Others apparently arise from small GABA-positive cell bodies which are scattered among principal neurons, within clusters of SIF cells and in bundles of GABA-negative axons. The majority of these cells is located in the lower half of the ganglion complex. Principal neurons did not react with antibodies against GABA or GAD. An unevenly distributed mesh-work of GABA-immunoreactive axons was seen in each of the ganglia. Immunoreactive axons formed numerous varicosities. Some of them were aggregated in a basket-like form around a subpopulation of GABA-negative principal ganglion cell bodies. Electron-microscopic immunocytochemistry revealed that GABA-positive nerve fibers establish asymmetric synaptic junctions with dendritic and somatic spines of principal neurons, whereas postsynaptic densities are inconspicuous or absent on dendritic shafts and somata. The results suggest that in the cervical sympathetic ganglion complex principal neurons are not GABAergic, but are innervated by axons which react with both antibodies against GAD and/or GABA antibodies and originate from a subpopulation of small neurons.

Animals↗

[Ultrastructural morphometric analysis of the spiral ganglion in guinea pigs (author's transl)].

This is the first morphometric analysis of the cochlear spiral ganglion. Therefore the ganglion was subdivided in precisely defined compartments. We found that the normal, untreated spiral ganglion in guinea pigs contains 58% ganglion cells of the granular type, 26% satellite cells and Schwann cells, 8.6% extracellular space, 6.4% myelinated nerve fibers and 1% ganglion cells of the filamentous type. The granular ganglion cell consists in 83% out of cytoplasm and in 17% out of nuclei. The cytoplasm is containing 13% ribosomes, 12% mitochondria, 10% RER, 2.1% Golgi apparatus, 1.3% lysosomes. Based on these quantitative datas we expect to detect alterations of the normal structure earlier and more precisely under pathophysiological conditions as before.

Animals↗

Substance P-like immunoreactivity in the trigeminal ganglion. A fluorescence, light and electron microscope study.

The trigeminal ganglion of rat and guinea pig was studied for the presence of immunoreactive substance-P using fluorescence, light and electronmicroscopy. In untreated animals substance P containing cells, with a diameter of 15 to 50 micron, were distributed throughout the ganglion and comprised 10-30% of all ganglion cells. Colchicine, injected intraventricularly to inhibit intra-axonal transport, had no effect on the number of substance P cells; but when the drug was injected directly into the posterior root of the ganglion, the proportion of these cells increased to as much as 50%. In the electron microscope, immunoreactive substance-P was confined to ganglion cells classified as B type according to the arrangement of subcellular organelles, and to unmyelinated nerve fibers. Subcellularly the immunoreactivity appeared in cytoplasmic vesicles, as well as dispersed in the nerve fibers and the perikarya of neurons. The great number of substance P immunoreactive ganglion cells suggests that they do not comprise a well defined subpopulation of the B-cells. However, the immunoreactivity was restricted to a distinct ultrastructural type of neurons with unmyelinated nerve fibers, suggesting that they also may share some distinct functions.

Animals↗

Immunohistochemistry of biogenic polypeptides in nerve cells and fibres of the guinea pig inferior mesenteric ganglion after perturbations.

Immunohistochemistry of peptide- and dopamine-beta-hydroxylase-(DBH)-containing varicose nerve fibres and ganglion cells, respectively, in the guinea pig inferior mesenteric ganglion was investigated following a) transsection of mesenteric (colonic) branches, b) transsection of central (lumbar splanchnic, intermesenteric and hypogastric) branches, and c) transplantation into the spleen. The findings indicate that pathways of different opioid peptides are not identical. Met-enkephalin- and met-enkephalin-arg-phe- (cleavage products from pre-proenkephalin) containing fibres course in central branches to make contact in the inferior mesenteric ganglion. Dynorphin- and alpha-neo-endorphin- (deriving from pre-prodynorphin) containing fibres as well as leu-enkephalin- (included in the dynorphin sequence) fibres appear to rise not only from central and from enteric somata, but also from intraganglionic noradrenergic neurons. Similar pathways seem to be used by VIP- and by neurotensin-immunoreactive fibres, although intraganglionic neurotensin-immunoreactive cell bodies are rare. Practically all substance P- and most CGRP-immunoreactive fibres enter the ganglion via central branches and, to a large extent, traverse it, but some CGRP-immunoreactive influx appears to come from the intestine. The origin of intraganglionic substance P- and CGRP-immunoreactive fibres after ganglion transplantation remained unidentified. Somatostatin- and neuropeptide Y-immunoreactive fibres predominantly have an intraganglionic origin as have DBH-immunoreactive noradrenergic fibres. The demonstrated alterations in neuropeptide immunoreactivity of intraganglionic and periganglionic nerve fibres following the applied transsection procedures contribute to the present knowledge on origin and destination of peptidergic transmitter segments in the guinea pig inferior mesenteric ganglion. Moreover, the present study provides evidence that intrinsic participation in intraganglionic fibre supply is more extensive than hitherto believed.

Animals↗