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Anatomy of the mushroom bodies in the honey bee brain: the neuronal connections of the alpha-lobe.

Neural connections between the mushroom body (MB) and other protocerebral areas of the honeybee's brain were studied with the help of cobalt chloride and Golgi staining methods. Focal injections of cobalt ions into the alpha-lobe neuropil of the MB reveal seven clusters of somata located in the protocerebrum and deutocerebrum of each brain hemisphere. These neurons connect the mushroom body neuropil with protocerebral areas and number approximately 400. They contact the layered organization of the alpha-lobe at different locations. Some project not only into the alpha-lobe, but also into the beta-lobe and pedunculus neuropils. Fifteen cell types which form intraprotocerebral circuits are morphologically described. They can be divided into three categories: 1) unilateral neurons, with projection fields restricted to the ipsilateral protocerebrum; these neurons connect the alpha-lobe with areas in the protocerebral lobe and ramify with densely layered arborisations arranged perpendicularly to the longitudinal axis of the alpha-lobe; 2) recurrent neurons, which interconnect subcompartments of the MB, forming loops at different levels of the neuropil; their arborisations are mainly restricted to the alpha-lobe, beta-lobe, pedunculus, and calyces of the ipsilateral MB; they also ramify sparsely around the neuropil of the alpha-lobe; and 3) bilateral neurons, which either interconnect both alpha-lobes or connect the ipsilateral alpha-lobe and protocerebral lobe with the dorsolateral protocerebral lobe of the contralateral hemisphere. The connections of different compartments of the MB with other parts of the protocerebrum as revealed in this study are discussed in the context of hypotheses about the functional role of MBs in the honeybee brain.

Animals↗

Neuronal connections of the area postrema.

The literature dealing with the neuronal connections of the area postrema (AP) is reviewed. Although it has been suggested that many regions of the central nervous system are directly connected with the AP, convincing evidence exists for only a few such regions. Afferent projections have been described from specific components of the vagus and glossopharyngeal nerves, and efferent connections have been reported to the nucleus tractus solitarii and to the parabrachial nuclei. In addition, an indirect projection from the AP to the dorsal motor nucleus of the vagus nerve exists. Further study is necessary to establish whether other important connections occur, and to determine if the connectivity of the AP is consistent in various species.

Afferent Pathways↗

GABAA-mediated local synaptic pathways connect neurons in the rat suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) in mammals functions as the biological clock controlling circadian rhythms, but the synaptic circuitry of the SCN is largely unexplored. Most SCN neurons use the neurotransmitter gamma-aminobutyric acid (GABA), and anatomic studies indicate many GABAergic synapses and local axon collaterals; however, physiological evidence for synaptic communication among SCN neurons is indirect. We have used three approaches to investigate local circuitry in the SCN in acute hypothalamic slices from rat. First, tetrodotoxin was used to block action-potential-dependent synaptic release, which resulted in a decrease in the frequency of spontaneous synaptic currents in SCN neurons, suggesting that spontaneously active neurons in the slice connect synaptically to SCN neurons. Postsynaptic currents in SCN neurons were also evoked by the selective stimulation of other SCN neurons with glutamate, which avoids direct activation of axons that might originate outside the SCN. Two different methods of glutamate microapplication (i.e., pressure ejection and ultraviolet photolysis of caged glutamate) indicated that SCN neurons receive GABAA-receptor-mediated synaptic input from other SCN neurons. In contrast, glutamate-receptor-mediated synaptic connections between SCN neurons were not detected. The GABAergic synapses that comprise the network described here could conceivably be a substrate for the synchronization and amplification of the circadian rhythm of SCN firing. Alternatively, this circuitry might mediate other aspects of clock function such as the integration of environmental and physiological information.

Animals↗

Neuronal connections in the primary auditory cortex: an electrophysiological study in the cat.

Neuronal connections in the primary auditory cortex (AI) of the cat were studied electrophysiologically by using intracellular recording techniques. Fast-conducting fibers from the medial geniculate nucleus (MG) projected monosynaptically onto AI neurons in layers III-VI (mainly in layer IV), whereas slow-conducting MG-fibers projected monosynaptically onto AI neurons in layer I. AI neurons which received monosynaptic inputs from the auditory association cortices (AII and Ep) and/or from the contralateral AI were distributed in all layers of the AI; the commissural fibers from the contralateral AI were divided into fast- and slow-conducting ones. AI neurons were categorized into seven types: type I neurons which received monosynaptic inputs from slow-conducting MG-fibers were located in layer I. Type II neurons which received polysynaptic inputs from the MG were located in layers II-VI. Type III neurons which sent their axons to the AII or Ep were mainly located in layer III. Type IV neurons which sent their axons to the contralateral AI were located mainly in layer III. Type V neurons which received monosynaptic inputs from fast-conducting MG-fibers were located mainly in layer IV. Type VI neurons which projected onto the inferior colliculus were located in the upper part of the layer V. Type VII neurons which projected onto the MG were located in layers V and VI.

Animals↗

[Characteristics of the shape of auto- and cross-correlation histograms of the spike trains of polysynaptically connected neurons].

Peculiarities of auto- and cross-correlation histograms of spike trains of polysynaptically (disynaptically) connected neurones were studied by means of mathematical and biomathematical modelling of neuronal interaction (computer controlled experiment with neurones of a mollusc) in wide physiological diapazons of the values of parameters characterizing the properties and conditions of functioning of the neurones and synapses. A comparison was carried out of manifestations of polysynaptic and corresponding monosynaptic connections in auto- and cross-correlation histograms.

Action Potentials↗

CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein.

Neuronal plasticity requires actin cytoskeleton remodeling and local protein translation in response to extracellular signals. Rho GTPase pathways control actin reorganization, while the fragile X mental retardation protein (FMRP) regulates the synthesis of specific proteins. Mutations affecting either pathway produce neuronal connectivity defects in model organisms and mental retardation in humans. We show that CYFIP, the fly ortholog of vertebrate FMRP interactors CYFIP1 and CYFIP2, is specifically expressed in the nervous system. CYFIP mutations affect axons and synapses, much like mutations in dFMR1 (the Drosophila FMR1 ortholog) and in Rho GTPase dRac1. CYFIP interacts biochemically and genetically with dFMR1 and dRac1. Finally, CYFIP acts as a dRac1 effector that antagonizes FMR1 function, providing a bridge between signal-dependent cytoskeleton remodeling and translation.

Adaptor Proteins, Signal Transducing↗

Postnatal development of neuronal connections in cat visual cortex studied by intracellular recording in slice preparation.

Postnatal development of neuronal connections in cat visual cortex (area 17) was studied in slice preparations obtained from kittens aged 1-18 weeks after birth and adult cats by recording intracellularly excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP) evoked in cortical cells by stimulation of white matter. The EPSPs were already present in all cells at 1 week of age. Their efficiency assessed by their maximum rate of rise was low initially and increased progressively with age. In contrast, the IPSPs were absent in half of the cells at 1 week and almost all of the cells came to demonstrate inhibition by 9 weeks except for a few layer II-III cells. At all ages about three-quarters of the IPSPs had GABAA-mediated early and GABAB-mediated late components with different time courses, reversal potential and sensitivity to GABA antagonists, while the remaining IPSPs had only the early component. The efficiency of both IPSPs assessed by the associated conductance increase showed an increase of more than twice from 1 to 5 weeks, reaching the same level as adults. The time course of the development of inhibition demonstrated in this study paralleled the time course of the development of selective visual responsiveness in cortical cells, suggesting that the postnatal maturation of inhibitory connections is a basis of maturation of visual responsiveness.

Aging↗

Neuronal connections of the paratrigeminal nucleus: a topographic analysis of neurons projecting to bulbar, pontine and thalamic nuclei related to cardiovascular, respiratory and sensory functions.

The paratrigeminal nucleus, which receives sensory input from trigeminal, glossopharyngeal and vagus nerves, has efferent projections to bulbar, pontine and possibly to thalamic structures associated with nociception, thermoregulation and cardiovascular control. Anterograde neuronal tracers were used to study paratrigeminal efferent connections. Labeled terminal fibers, evidencing bilateral efferent paratrigeminal projections were observed in the medial and caudal solitary tract (sol), lateral reticular nucleus (LRt), ambiguus nucleus (Amb), rostroventrolateral reticular nucleus (RVL), while ipsilateral projections were found in the parabrachial (PB) nuclei and ventral portion of the ventral posteromedial thalamic nucleus (VPM). This extends other findings that describe paratrigeminal projections. Retrograde neuronal transport tracers, microinjected in the defined projection areas were used to map distribution of the paratrigeminal neurons originating different efferent connections. Microinjection of latex microspheres containing fluorescein or rhodamine and Fluoro-gold in the ventral VPM, PB, RVL, Amb, LRt and NTS revealed sets of labeled paratrigeminal nucleus neurons respectively organised in a rostral-caudal sequence. The largest extent of the paratrigeminal nucleus (medial portion) contained neurons projecting to the RVL/Amb, structures associated with cardiovascular regulation. The data show a segmented topographical organization of the nucleus, with different sets of neurons within delimited segments, projecting to neuronal structures associated with different functions. This points to a complex and extensive role for the paratrigeminal nucleus in the integration of somatosensory reflexes related to cardiovascular, respiratory and pain mechanisms. The nucleus may act as a medullary relay interposed between sensory afferents and different structures related to homoeostatic functions.

Animals↗

Non-Gaussian behavior of the EEG in Down's syndrome suggests decreased neuronal connections.

Computer analyses of the electroencephalograms of normal children, and children with Down's syndrome who were mentally retarded, revealed differences in the distribution of amplitude between the two groups. Normal children, in the early postnatal period, generate EEG's which have a non-Gaussian distribution of amplitude that becomes increasingly Gaussian before one year of age and remains so throughout subsequent development. Conversely, the EEG's of children with Down's syndrome exhibit highly non-Gaussian properties at all ages studied. The EEG's of two mentally retarded autistic children did not show this property, so it is not merely a concomitant of mental retardation. The first-order Gaussian distribution may reflect the degree of inteneuronal coupling; since an increased number of connections on any neuron implies decreased functional dependence of that neuron on any other particular single neuron, the present evidence, which indicates stronger interneuronal coupling in mongoloids, suggests that Down's syndrome may be associated with incomplete postnatal development of interconnections between cortical neurons.

Autistic Disorder↗

An experimental study of the ventral striatum of the golden hamster. II. Neuronal connections of the olfactory tubercle.

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the olfactory tubercle. Following iontophoretic applications or hydraulic injections of HRP in the tubercle, neurons labeled by retrograde transport of HRP were observed ipsilaterally in the telencephalon in the main olfactory bulb, the medial, lateral, ventral, and posterior divisions of the anterior olfactory nucleus, and in the orbital, ventral, and posterior agranular insular, primary olfactory, perirhinal, and entorhinal cortices. Labeled cells were also present in the basolateral, basomedial, anterior cortical, and posterolateral cortical amygdaloid nuclei, and bilaterally in the nucleus of the lateral olfactory tract. In the diencephalon, ipsilateral HRP-containing neurons were observed in the midline nuclei paraventricularis, parataenialis, and reuniens, and in the parafascicular intralaminar nucleus. Retrograde labeling was present in the ipsilateral brainstem in cells of the ventral tegmental area, substantia nigra, and dorsal raphe. Many of the above projections to the tubercle were found to be topographically organized. Anterograde axonal transport of HRP from the olfactory tubercle labeled terminal fields ipsilaterally in all parts of the anterior olfactory nucleus, in the ventral pallidum, and in the substantia nigra, pars reticulata. Contralaterally, terminal fields were present in the dorsal and lateral divisions of the anterior olfactory nucleus. The projections to the tubercle from the orbital, ventral, and posterior agranular insular, and perirhinal neocortices, intralaminar thalamus, and dopamine-containing areas of the ventral mesencephalon are analogous to the connections of the caudatoputamen, as are the efferents from the tubercle to the ventral globus pallidus and substantia nigra. These connections substantiate the recent suggestion that the olfactory tubercle is a striatal structure, and provide support for the ventral striatal concept. In the present study of the olfactory tubercle, and in the first study in this series on the nucleus accumbens, the ventral striatum was found to receive projections from a number of limbic system structures, including the main olfactory bulb, anterior olfactory nucleus, amygdala, hippocampus, and subiculum, and the entorhinal and primary olfactory cortices. These findings suggest that the ventral striatum is concerned with integrating limbic information into the striatal system.

Amygdala↗

Establishment of neuronal connectivity during development of the Drosophila larval visual system.

We used confocal microscopy in conjunction with specific antibodies and enhancer trap strains to investigate the development of specific neuronal connections in a simple model system, the larval visual system of Drosophila. We find that the establishment of axonal projections from the larval photoreceptor neurons to their central nervous system targets involves a series of discrete steps. During embryogenesis, the larval optic nerve contacts several different cell types, including optic lobe pioneer (OLP) neurons and a number of glial cells. We demonstrate that OLP neurons are present and project normally in glass (gl) mutant embryos in which the larval optic nerve fails to develop, suggesting that they do not depend on interactions with the larval optic nerve for differentiation and proper axonal projection. The OLPs fail to differentiate properly is disconnected (disco) mutant embryos, where appropriate connections between the larval optic nerve and its targets in the brain are not formed. The disco gene is expressed in the OLPs and may therefore act autonomously to direct the differentiation of these cells. Taken together, our results suggest that the OLPs act as an intermediate target required for the establishment of normal optic nerve projection and connectivity.

Animals↗

Aberrant neuronal connectivity in CHL1-deficient mice is associated with altered information processing-related immediate early gene expression.

In humans, loss or alteration of the CHL1/CALL gene may contribute to mental impairment associated with the 3p-syndrome, caused by distal deletions of the short (p) arm of chromosome 3, and schizophrenia. Mice deficient for the Close Homologue of L1 (CHL1) show aberrant connectivity of hippocampal mossy fibers and olfactory sensory axons, suggesting participation of CHL1 in the establishment of neuronal networks. Furthermore, behavioral studies showed that CHL1-deficient mice react differently towards novel experimental environments. These data raise the hypothesis that processing of information, possibly novel versus familiar, may be altered in the absence of CHL1. To test this hypothesis, brain activities were investigated after presentation of a novel, familiar, or neutral gustatory stimulus using metabolic mapping with ((14)C)-2-deoxyglucose (2-DG) and analysis of mRNA expression of the immediate early genes (IEGs) c-fos and arg 3.1/arc by in situ hybridization. 2-DG labeling revealed only small differences between CHL1-deficient and wild-type littermate mice. In contrast, while the specific novelty-induced increase in c-fos expression was maintained in most of the brain areas analyzed, c-fos mRNA expression was similar after the novel and familiar taste in several brain areas of the CHL1-deficient mice. Furthermore, in these mutants, arg 3.1/arc expression was slightly reduced after the novel taste and increased after the familiar taste, leading to a similar arg 3.1/arc mRNA expression after both stimuli. Our results indicate that, in contrast to controls, CHL1-deficient mice might process novel and familiar information similarly and suggest that the altered neuronal connectivity in these mutants disturbs information processing at the molecular level.

Animals↗

An experimental study of the ventral striatum of the golden hamster. I. Neuronal connections of the nucleus accumbens.

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the nucleus accumbens. Following iontophoretic applications or hydraulic injections of HRP in nucleus accumbens, cells labeled by retrograde transport of HRP were observed in the ipsilateral telencephalon in the posterior agranular insular, perirhinal, entorhinal, and primary olfactory cortices, in the subiculum and hippocampal field CA1, and in the anterior and posterior divisions of the basolateral amygdaloid nucleus. In the diencephalon, labeled neurons were present ipsilaterally in the central medial, paracentral and parafascicular intralaminar nuclei, and in the midline nuclei parataenialis, paraventricularis, and reuniens. Retrograde labeling was observed in the ipsilateral brainstem in cells of the ventral tegmental area and dorsal raphe. Many of these projections to nucleus accumbens were found to be topographically organized. Anterograde transport of HRP from nucleus accumbens demonstrated ipsilateral terminal fields in the ventral pallidum and substantia nigra, pars reticulata. The afferent projections to nucleus accumbens from the posterior insular and perirhinal neocortices, intralaminar thalamus, and the dopamine-containing ventral tegmental area are analogous to the connections of the caudatoputamen, as are the efferents from nucleus accumbens to the substantia nigra and ventral globus pallidus. These connections substantiate the classification of nucleus accumbens as a striatal structure and provide support for the recently proposed concept of the ventral striatum. Furthermore, the demonstration that a number of limbic system structures, including the amygdala, hippocampal formation, entorhinal cortex, and olfactory cortex are important sources of afferents to the nucleus accumbens, suggests that the ventral striatum may serve to integrate limbic information into the striatal system.

Amygdala↗

Plasticity of neuronal connections in developing brains of mammals.

Although mature nervous systems show substantial malleability following various surgical or environmental manipulations, developing brains show far more prominent plasticity, particularly in terms of morphological features. Neuronal circuits, for example, can be dramatically rewired following neonatal but not adult brain lesions. It remains unknown why neuronal circuits in developing brains show such remarkable plasticity. A number of anatomical and physiological studies suggest that there are transient projections in developing brains and they are eliminated by cell death and/or collateral elimination as development proceeds. This raises a possibility that aberrant projections observed following various surgical or environmental manipulations such as partial denervation, results from retention or stabilization of transient projections. However, evidence suggests that cell death does not play an important role in developmental fine-tuning of neuronal projections. Furthermore, although the elimination of axon collaterals takes place, individual neurons appear to elaborate axonal arbors in appropriate target areas, resulting in a net increase in the size of axonal arbor emerging from individual neurons. In accord with these observations, the number of synapses appear to increase during the period when axonal elimination proceeds. Taken together, reinforcement of appropriate projections rather than elimination of excessive connections plays a major role in developmental specification of neuronal connections. Appearance of aberrant projections after partial denervation may not be a consequence of disordered axonal growth, since they form topographic maps which precisely mirrors those for normal projections. They may be induced due to reinforcement of pre-existing neuronal connections rather than to construction of novel pathways. Observations of axonal morphology in denervated areas indicate that lesion-induced enlargement of projections is due to transformation of axonal morphology, from simple and poorly branched to multiply branched. Perhaps such simple and poorly branched axons in inappropriate target areas may represent ones in the course of elimination but they may serve as a source of sprouting when denervated. In other words, after total elimination of axons any surgical or environmental manipulation cannot induce enlargement of projections. The mechanisms underlying such modifiability of neuronal connections remains unclarified but possible participation of an activity-dependent competitive mechanism is discussed.

Animals↗

The receptor tyrosine kinase Off-track is required for layer-specific neuronal connectivity in Drosophila.

The nervous system in many species consists of multiple neuronal cell layers, each forming specific connections with neurons in other layers or other regions of the brain. How layer-specific connectivity is established during development remains largely unknown. In the Drosophila adult visual system, photoreceptor (R cell) axons innervate one of two optic ganglia layers; R1-R6 axons connect to the lamina layer, while R7 and R8 axons project through the lamina into the deeper medulla layer. Here, we show that the receptor tyrosine kinase Off-track (Otk) is specifically required for lamina-specific targeting of R1-R6 axons. Otk is highly expressed on R1-R6 growth cones. In the absence of otk, many R1-R6 axons connect abnormally to medulla instead of innervating lamina. We propose that Otk is a receptor or a component of a receptor complex that recognizes a target-derived signal for R1-R6 axons to innervate the lamina layer.

Aging↗

Lucifer yellow-CH identification of a primary neuron connecting the first segmental nerve to the three giant axons in the nerve cord of the earthworm Amynthas hawayanus.

This is the first step in the identification of a primary or first-order neuron connecting terminal organs, such as receptors or muscle, to interneurons, such as giant axons. The preparation employed here was a single segment of the ventral nerve cord between the 30th and the 40th segment, with a single first segmental nerve connected. A small drop of 7% Lucifer Yellow-CH was placed at the cut end of the first nerve in the absence of detergent or electric current. A structured complex could be seen in the cord anterior to the first nerve after one or two min backfilling. Several long processes extend from this structure to the contralateral side of the nerve cord and terminate in button-like structures near the medial giant axon and the contralateral lateral giant axon. The afferent or efferent function of this neural complex remains to be determined.

Animals↗

A catecholaminergic neuron connecting the first two optic neuropiles (lamina ganglionaris and medulla externa) of the crayfish pacifastacus leniusculus.

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 alpha-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.

Animals↗

The timecourse of neuronal connections of the rotundoectostriatal pathway in chicks (Gallus gallus) during embryogenesis: a retrograde transport study.

The avian retinotectofugal pathway has been suggested to be homologous to the mammalian retinotectofugal pathway. The projection of the nucleus rotundus upon the ectostriatum is equivalent to that of the pulvinar nucleus upon the extrastriate cortex in mammals. In this system, the optic tectum relays retinal input to the nucleus rotundus, which then ascends to the ectostriatum of the telencephalon. Given the fact that the chick retinotectofugal system becomes mature early during development, the present study attempted to investigate the timecourse of neuronal connections of the embryonic rotundoectostriatal pathway. We used multiple injections of cholera toxin B subunit (CTb) in the ectostriatum of chick embryos to retrogradely trace projections to the nucleus rotundus. We found CTb-labeled neurons in the nucleus rotundus at embryonic day 7.5-8. By embryonic day 8-8.5, increased numbers of CTb-labeled neurons were seen in the nucleus rotundus. It was noted that the time of this initial connection between the nucleus rotundus and the ectostriatum is nearly synchronous with that of the retinotectal and tectorotundal pathways, respectively (Crossland et al., 1975; Thanos & Bonhoeffer, 1987; Wu et al., 2000). These findings, combined with the present study, suggest that the retinotectofugal system becomes established, at least at a structural level, by embryonic day E8.

Animals↗