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PubMed1980

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↗

PubMed2005

WNTs in the vertebrate nervous system: from patterning to neuronal connectivity.

WNT signalling has a key role in early embryonic patterning through the regulation of cell fate decisions, tissue polarity and cell movements. In the nervous system, WNT signalling also regulates neuronal connectivity by controlling axon pathfinding, axon remodelling, dendrite morphogenesis and synapse formation. Studies, from invertebrates to mammals, have led to a considerable understanding of WNT signal transduction pathways. This knowledge provides a framework for the study of the mechanisms by which WNTs regulate diverse neuronal functions. Manipulation of the WNT pathways could provide new strategies for nerve regeneration and neuronal circuit modulation.

Animals↗

PubMed2006

A signaling network for patterning of neuronal connectivity in the Drosophila brain.

The precise number and pattern of axonal connections generated during brain development regulates animal behavior. Therefore, understanding how developmental signals interact to regulate axonal extension and retraction to achieve precise neuronal connectivity is a fundamental goal of neurobiology. We investigated this question in the developing adult brain of Drosophila and find that it is regulated by crosstalk between Wnt, fibroblast growth factor (FGF) receptor, and Jun N-terminal kinase (JNK) signaling, but independent of neuronal activity. The Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a Branchless (FGF)-Breathless (FGF receptor) axon-retracting signal to modulate JNK activity. JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern.

Adaptor Proteins, Signal Transducing↗

PubMed1992

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↗

PubMed2004

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↗

PubMed1988

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↗

PubMed1977

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↗

PubMed2005

Neuronal connection of the cortex and reconstruction of the visual space.

The distributions of retrograde labeled cells in fields 17 and 18 and the fields 17/18 transitional zone were studied in both hemispheres of cats after microiontophoretic administration of horseradish peroxidase into individual cortical columns in fields 17, 18, 19, and 21a. The clustered organization of the internal connections of the cortical fields, the asymmetrical locations of labeled callosal cells relative to the injected columns, and the defined distribution of labeled cells in layers A of the lateral geniculate body suggested that eye-specific neuronal connections support "binding" of the visual hemifields separately for each eye. Application of marker to columns in fields 19 or 21a demonstrated disparate inputs from fields 17 and 18 and the fields 17/18 transitional zone. It is suggested that these connections may support the extraction of loci and stereoscopic boundaries located in the central sectors of the visual space.

Animals↗

PubMedDate not supplied

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↗

PubMed2004

WAVE/SCAR, a multifunctional complex coordinating different aspects of neuronal connectivity.

Although it is well established that the WAVE/SCAR complex transduces Rac1 signaling to trigger Arp2/3-dependent actin nucleation, regulatory mechanisms of this complex and its versatile function in the nervous system are poorly understood. Here we show that the Drosophila proteins SCAR, CYFIP and Kette, orthologs of WAVE/SCAR complex components, all show strong accumulation in axons of the central nervous system and indeed form a complex in vivo. Neuronal defects of SCAR, CYFIP and Kette mutants are, despite the initially proposed function of CYFIP and Kette as SCAR silencers, indistinguishable and are as diverse as ectopic midline crossing and nerve branching as well as synapse undergrowth at the larval neuromuscular junction. The common phenotypes of the single mutants are readily explained by the finding that loss of any one of the three proteins leads to degradation of its partners. As a consequence, each mutant is unambiguously to be judged as defective in multiple components of the complex even though each component affects different signaling pathways. Indeed, SCAR-Arp2/3 signaling is known to control axonogenesis whereas CYFIP signaling to the Fragile X Mental Retardation Protein fly ortholog contributes to synapse morphology. Thus, our results identify the Drosophila WAVE/SCAR complex as a multifunctional unit orchestrating different pathways and aspects of neuronal connectivity.

Adaptor Proteins, Signal Transducing↗

PubMed2003

[Cortical neuronal connections and reconstruction of visual space].

We investigated distribution of retrograde-labelled cells in cortical areas 17, 18, and the transition zone 17/18 of both hemispheres in cats after microiontophoretic horseradish peroxidase (HRP) injections into the single cortical columns of area 17, 18, 19 or 21a. On the base of clustered pattern of intrinsic labelling, asymmetric location of labelled callosal cells that was associated with the appropriate pattern of labelling in layers A and A1 of lateral geniculate nucleus, we suggest that cortical neuronal connections are eye-specific and may provide for each eye a separate binding of visual hemifields. After HRP injections into columns of area 19 or 21a, the disparate inputs from areas 17, 18 and transition zone 17/18 were revealed. Such connections may provide a local depth information and the selection of stereoscopic surfaces in central sectors of visual space.

Animals↗

PubMed2005

Decreased sensory stimulation reduces behavioral responding, retards development, and alters neuronal connectivity in Caenorhabditis elegans.

Activity-dependent plasticity is a critical component of nervous systems. We show that in Caenorhabditis elegans, worms raised in isolation made smaller responses to mechanosensory stimulation and were smaller and slower to begin laying eggs than age-matched group-raised worms. The glutamate receptor gene GLR-1 was critical for the observed alterations in behavior but not in size, whereas the cGMP-dependent protein kinase gene EGL-4 was critical for the observed changes in size but not the changes in behavior. Mechanosensory stimulation during development reversed the effects of isolation on behavior and began to reduce the effects of isolation on size. In C. elegans, the six mechanosensory touch neurons synapse onto the four pair of command interneurons for forward and backward movement. Touch (mechanosensory) neurons of worms raised in isolation expressed lower levels of green fluorescent protein (GFP)-tagged synaptobrevin than touch neurons of worms raised in colonies. Command interneurons of worms raised in isolation expressed lower levels of GFP-tagged glutamate receptors than command interneurons of worms raised in groups. Brief mechanical stimulation during larval development rescued the expression of GFP-tagged glutamate receptors but not GFP-tagged synaptobrevin. Together, these results indicate that the level of stimulation experienced by C. elegans during development profoundly affects the development of neuronal connectivity and has widespread cellular and behavioral consequences.

Animals↗

PubMed1997

Viral labelling of synaptically connected neurons.

A method has recently been developed to study the neuroanatomical connections in the brain by trans-synaptic tract-tracing via neurotropic viruses. Neurotrop viruses injected into a peripheral organ or directly into the central nervous system are transported axonally. Viruses are expressed in the infected neurons and they are transferred through synapses to reach other neurons. Many research studies illustrate by immunocytochemical detection of the viral proteins that the trans-synaptically interconnected neurons can be visualized, in addition, their neurochemical character can be identified. Thus, viruses could serve as a self-amplifying specific markers of connected neurons along hierarchial chains of functionally related circuits. Herein, we reviewed the methodology of the neuroanatomical studies obtained with a member of a-herpes viruses, the pseudorabies virus, frequently used in tracer studies in rats.

Animals↗

PubMed2000

A genetic programme for neuronal connectivity.

What is the nature of the genetic programme that allows neurons to extend their axons and connect to other neurons with a high degree of specificity? Work on the sensory neurons of the fly has shown how the control of neuronal identity is embedded in the general developmental programme of the organism. The ongoing analysis of pathfinding mutants suggests plausible mechanisms for the translation of neuronal identity into axonal behaviour.

Animals↗

PubMed2006

The cadherin superfamily in neuronal connections and interactions.

Neural development and the organization of complex neuronal circuits involve a number of processes that require cell-cell interaction. During these processes, axons choose specific partners for synapse formation and dendrites elaborate arborizations by interacting with other dendrites. The cadherin superfamily is a group of cell surface receptors that is comprised of more than 100 members. The molecular structures and diversity within this family suggest that these molecules regulate the contacts or signalling between neurons in a variety of ways. In this review I discuss the roles of three subfamilies - classic cadherins, Flamingo/CELSRs and protocadherins - in the regulation of neuronal recognition and connectivity.

Animals↗

PubMed1992

Identification of neuronal connections by means of electron microscopic immunocytochemistry.

For many years neuroanatomical research has focused on the tracing of connections between populations of neurons in the central nervous system. With the development of immunocytochemical procedures employing antibodies against transmitters, transmitter-synthesizing enzymes and various neuropeptides, it has become possible to study the chemical characteristics of nerve cells. By combining tracer techniques and immunocytochemical approaches the transmitter identity of a projection can be determined. Moreover, electron microscopic double-labeling procedures allow the identification of the target cells of immunocytochemically characterized presynaptic terminals. This way, by the immunocytochemical identification of transmitters or neuropeptides in defined projection neurons, a more functional interpretation of neuroanatomical data has become possible. In the present report, these combinations of techniques are demonstrated by describing recent studies of cholinergic septohippocampal projection neurons.

Animals↗

PubMed2003

Morphometric analysis of the columnar innervation domain of neurons connecting layer 4 and layer 2/3 of juvenile rat barrel cortex.

We have investigated the dendritic and axonal morphology of connected pairs of L4 spiny neurons and L2/3 pyramidal cells in rat barrel cortex. The 'projection' field of the axons of L4 spiny neurons in layers 2/3, 4 and 5 has a width of 400-500 microm thereby defining an anatomical barrel-column. In layer 2/3, the averaged axonal 'projection' field of L4 spiny neurons together with the dendritic 'receptive' field of the connected L2/3 pyramidal cells form a mostly column-restricted anatomical L4-to-L2/3 'innervation domain' that extends 300-400 microm and includes mostly basal dendrites. In the L4-to-L2/3 innervation domain a single L4 spiny neuron contacts approximately 300-400 pyramidal cells while in the L4-to-L4 innervation domain it contacts approximately 200 other L4 spiny neurons. Similarly approximately 300-400 L4 spiny neurons converge onto a single pyramidal cell and approximately 200 L4 spiny neurons innervate another L4 spiny neuron. The L2/3 pyramidal cell axon has a vertical projection field spanning all cortical layers, and a long-range horizontal field in layers 2/3 (width 1,100-1,200 microm) and 5 (700-800 microm) projecting across column borders. The results suggest that the flow of excitation within a barrel-column is determined by the largely columnar confinement of the L4-to-L4 and L4-to-L2/3 innervation domains. A whisker deflection activates approximately 140 L4 spiny neurons that will generate EPSPs in most barrel-related L2/3 pyramidal cells of a principal whisker column. The translaminar synaptic transmission to layer 2/3 and the axonal projection fields of L2/3 pyramidal cells are the major determinants of the dynamic, multi-columnar map in which a single whisker deflection is represented in the cortex.

Age Factors↗

PubMed1998

Neuronal connections between the auricular skin and the sympathetic pre- and postganglionic neurons of the dog as studied by using pseudorabies virus.

Pseudorabies virus (PrV) as a neuronal tracer was microinjected into the concave surface of the puppy's left pinna to establish the morphological basis of somato-visceral linkage. The virus infected neurons were detected by FITC conjugated with polyclonal swine anti-PrV serum. Labelled neurons were localized in: (1) the trigeminal, geniculate and superior vagal ganglia; (2) the subnucleus caudalis of the spinal trigeminal nucleus; (3) the intermediolateral column (IML) of the thoracolumbar segments and (4) the sympathetic chain ganglia. Present results suggest that when injected into the peripheral nerves, PrV was retrogradely transported to the nerve cell bodies located in the respective sensory ganglia. From the first order sensory neurons, the virus would self-replicate and was transported trans-synaptically via the brainstem nuclei and IML to reach the neurons in the sympathetic ganglia.

Animals↗