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At least 397 records · Page 22Linked to original sources
PubMed2006

Long-term motor cortex plasticity induced by an electronic neural implant.

It has been proposed that the efficacy of neuronal connections is strengthened when there is a persistent causal relationship between presynaptic and postsynaptic activity. Such activity-dependent plasticity may underlie the reorganization of cortical representations during learning, although direct in vivo evidence is lacking. Here we show that stable reorganization of motor output can be induced by an artificial connection between two sites in the motor cortex of freely behaving primates. An autonomously operating electronic implant used action potentials recorded on one electrode to trigger electrical stimuli delivered at another location. Over one or more days of continuous operation, the output evoked from the recording site shifted to resemble the output from the corresponding stimulation site, in a manner consistent with the potentiation of synaptic connections between the artificially synchronized populations of neurons. Changes persisted in some cases for more than one week, whereas the output from sites not incorporated in the connection was unaffected. This method for inducing functional reorganization in vivo by using physiologically derived stimulus trains may have practical application in neurorehabilitation after injury.

Action Potentials↗
PubMed1997

Beta-galactosidase-labelled relay neurons of homotopic olfactory bulb transplants establish proper afferent and efferent synaptic connections with host neurons.

The vertebrate olfactory system has long been an attractive model for studying neuronal regeneration and adaptive plasticity due to the continuous neurogenesis and synaptic remodelling throughout adult life in primary and secondary olfactory centres, its precisely ordered synaptic network and accessibility for manipulation. After homotopic transplantation of fetal olfactory bulbs in bulbectomized neonatal rodents, newly regenerated olfactory neurons form glomeruli within the graft, and the efferent mitral/tufted cells of the transplant innervate the host brain, terminating in higher olfactory centres. However, the synaptic connections of the transplanted relay neurons within the graft and/or host's olfactory centres could not be characterized mainly because of lack of suitable cell-specific markers for these neurons. In this study, we have used olfactory bulbs from transgenic fetuses, in which the majority of the mitral/tufted cells express the bacterial enzyme beta-galactosidase, for homotopic olfactory bulb transplantation following complete unilateral bulbectomy. In the transplants, the cell bodies and terminals of the donor mitral/tufted cells were identified by beta-galactosidase histochemistry and immunocytochemistry at both light and electron microscope levels. We demonstrate that transplanted relay neurons re-establish specific synaptic connections with host neurons of the periphery, source of the primary signal and central nervous system, thereby providing the basis for a functional recovery in the lesioned olfactory system.

Afferent Pathways↗
PubMed1990

Competitive and positional cues in the patterning of nerve connections.

The visual system of lower vertebrates has served as an important testing ground for the mechanisms that generate topographic neuronal connections. During both the outgrowth and the regeneration of the optic nerve, a smoothly ordered map of the retina is formed on its major target, the optic tectum (the retinotectal projection). Experiments performed on this projection have offered support for a variety of mechanisms, including the matching of positional cues in the retina and tectum, the guidance of nerve fibers by interactions between fibers, competition for synaptic space, and the refinement of connections based on neuronal activity. Unfortunately, individual experiments that support any one of these mechanisms have been taken at times as evidence against the involvement of any other mechanism; for example, experiments demonstrating the importance of positional cues have been thought mistakenly to indicate that activity-based interactions are unimportant. Computer simulations, in which multiple, somewhat opposed, mechanisms are allowed to operate in concert demonstrate that such a hybrid model is able to generate a full range of experimental results. More importantly, the elimination of any one of the mechanisms renders the model unable to fit entire classes of findings. Thus, the patterning of the retinotectal projection is best viewed as a process in which the optic nerve terminals attempt to satisfy multiple constraints in selecting their target sites.

Animals↗
PubMed2003

To die or to sleep, perhaps to dream.

Establishing social contacts is the raison d'être of neurons throughout their entire life span. To form and retain functional connections, neuronal differentiation and death are ruthlessly regulated in development and kept strictly under control in post-mitotic systems. Derangements in neural networks affect neuronal populations at large. Therefore, failure to retain synaptic connectivity is linked to dysfunction and often followed by neuronal death. Loss of neurons is a predominant feature of neurodegenerative disease. Nevertheless, neuronal cell death is not an obligate requirement for neural dysfunction at the level of distributed circuits or local circuits. Although more or less wide spread neuronal loss can occur after acute insults such as brain ischemia or invasion of the brain by pathogens, neuronal death is a hallmark of end-stage neurodegenerative and psychiatric disease. The relative contributions made by loss of synaptic connectivity versus cell death for these diseases are still debated. Here these processes are discussed in relation to acute and chronic CNS disorders.

Apoptosis↗
PubMed1995

Epileptiform activity in the guinea-pig neocortical slice spreads preferentially along supragranular layers--recordings with voltage-sensitive dyes.

The spread of epileptiform activity was monitored in guinea-pig neocortical slices by the use of a voltage-sensitive dye (RH795) and a fast optical recording technique. Epileptiform activity induced by bicuculline methiodide (10-20 microM) and single-pulse stimulation spread from the stimulation site in layer I or in the white matter across most of the slice. Different lesions were made in the slice in order to specify the neuronal connections used for spread in the horizontal direction. In the slice, intracortical connections are necessary for the spread of epileptiform activity, as shown by vertical cuts through all cortical layers but sparing the white matter. Horizontal connections were interrupted by cuts parallel to the axis of pyramidal neurons through either supragranular or infragranular layers. Vertical connections were interrupted by cuts perpendicular to the axis of pyramidal neurons separating supragranular and infragranular layers. Spread of epileptiform activity in the horizontal direction was not hindered by horizontal cuts. Vertical cuts through infragranular layers also did not hinder the spread of epileptiform activity. In contrast, vertical cuts through supragranular layers either abolished completely (nine slices) or delayed significantly (ten slices) the spread of epileptiform activity. The mean delay at the supragranular lesion was 44 ms in layer III and 30 ms in layer V; at the infragranular lesion the mean delay was 2 ms in layer III and 6 ms in layer V. Also, with horizontal cuts, in three out of five slices the velocity of spread was significantly lower in infragranular as compared to supragranular layers. It is concluded that both supra- and infragranular layers if isolated possess the ability to initiate and propagate epileptiform activity independently. However, in the intact slice the influence of the supragranular networks on initiation and propagation of epileptiform activity appears to dominate.

Animals↗
PubMed1992

The developmental biology of neural connectivity.

How can the development of an ordered array of neuronal connections be encoded in the genome? Results on the establishment of sensory connections in insects indicate that this programming is a multi-stepped process which begins as soon as the first axons develop. Because each step relies on the previous level of organization, the first steps of the process are subject to intense structural constraints, and therefore have been largely conserved through evolution. What is known of the molecular biology of some essential steps, like the differentiation of excitable cells, their aggregation in nerve cords, and the diversification of a periodic structure, supports the idea that the basic organization of the CNS evolved before the divergence between the chordate and the arthropod/annelid lineage.

Animals↗
PubMed1984

The origin of postganglionic and sensory axons in the cervical sympathetic trunk of the cat: a horseradish peroxidase study.

The composition of the cervical sympathetic trunk (CST) in the cat is still not completely understood. The present study investigates, by the horseradish peroxidase (HRP) method of tracing neuronal connections, the presence of postganglionic and sensory neurons projecting via the CST. Following sympathectomy at the midcervical level and the application of HRP crystals to the cut ends of the CST which had been isolated from the surrounding by a 1.5% solution of agar-agar, labelled neurons were seen in the superior cervical (SCG), stellate (SG), inferior vagal ganglia (IVG), and spinal ganglia C8-T8. The maximum number of labelled neurons was 536 in the SCG, 460 in the SG, 180 in the IVG, and 104 in spinal ganglia C8-T8.

Animals↗
PubMed2001

Sensory modification of leech swimming: interactions between ventral stretch receptors and swim-related neurons.

The neuronal circuits that generate the leech swimming rhythm comprise oscillatory interneurons that provide appropriately phased output to drive swim-related motoneurons. Within ganglia, these interneurons express three phases; between ganglia there exists a phase delay between homologs. Our earlier experiments revealed that stretch receptors embedded in the body wall participate in intersegmental coordination and setting intersegmental phases. To identify the basis for these sensory effects, we mapped interactions between a ventral stretch receptor and swim-related neurons. Connections between this receptor and motoneurons are weak and variable in quiescent preparations, but during fictive swimming stretch receptor activation modulates motoneuron oscillations, hence, these effects are polysynaptic, mediated by interneurons. We identified a strong, nonrectifying, and apparently direct electrical connection between the stretch receptor and oscillator neuron 33. The ventral stretch receptor also interacts with most of the other oscillatory interneurons, including inhibitory inputs to cells 28 and 208, excitatory input to the contralateral cell 115, and mixed input to the ipsilateral cell 115. These direct and indirect interactions can account for previously described effects of body-wall stretch on motoneuron activity. They also could mediate the previously described modification of intersegmental phase relationships by appropriately phased stretch receptor activation.

Animals↗
PubMed2005

Is mood chemistry?

The chemical hypothesis of depression suggests that mood disorders are caused by a chemical imbalance in the brain, which can be corrected by antidepressant drugs. However, recent evidence indicates that problems in information processing within neural networks, rather than changes in chemical balance, might underlie depression, and that antidepressant drugs induce plastic changes in neuronal connectivity, which gradually lead to improvements in neuronal information processing and recovery of mood.

Affect↗
PubMed1999

Specific expression of ezrin, a cytoskeletal-membrane linker protein, in a subset of chick retinotectal and sensory projections.

Lamina-specific neuronal connections are a fundamental feature in many parts of the vertebrate central nervous system. In the chick, the optic tectum is the primary visual centre, and it has a multilaminated structure consisting of 15 laminae, of which only three or four receive retinal projections. Each of the retinorecipient laminae establishes synaptic connections selectively from one of a few subsets of retinal ganglion cells (RGCs). We have generated a series of monoclonal antibodies that appear to stain only one of the retinorecipient laminae. One of these, TB4, stained lamina F which receives inputs from a subpopulation of approximately 10-20% of RGCs which express the presynaptic acetylcholine receptor beta2-subunit. TB4 recognized a single 79-kDa protein on immunoblotting. cDNA cloning and immunochemical analysis revealed that the TB4 antigen molecule was ezrin, a cytoskeletal-membrane linker molecule belonging to the ezrin-radixin-moesin family. Unilateral enucleation of the eye, both prior to and after the establishment of retinotectal projections, attenuated the lamina-selective staining with TB4 in the contralateral tectum, suggesting that ezrin is anterogradely transported from RGCs to lamina F. Ezrin was thus expressed in a subset of RGCs that project to lamina F. Similar subset-selective expression and resultant lamina-selective distribution of ezrin were also observed in the lamina-specific central projections from the dorsal root ganglia. The staining pattern with TB4 in the dorsal root ganglia and spinal cord indicated that high expression of ezrin was restricted in cutaneous sensory neurons, but not in muscle sensory neurons. Since ezrin modulates cell morphology and cell adhesion profiles by linking membrane proteins with the cytoskeleton, it was suggested that ezrin is involved in the formation and/or maintenance of lamina-specific connections for neuronal subpopulations in the visual and somatosensory systems.

Amino Acid Sequence↗
PubMed1980

Connectivity changes in an isolated molluscan ganglion during in vivo culture.

The stability of neuronal connections in the isolated buccal ganglia of Helisoma trivolvis was examined during in vivo culture for periods up to one month. After 4--8 days the characteristic IPSP input to protractor motoneurons (PMNs) was either abolished or reduced in efficacy. This is apparently due to reduced efficacy of chemical synapses, since the input resistance and resting potential of the motoneurons is unchanged and a fraction of spike-evoked IPSPs from premotor neurons (cyberchrons) onto PMNs was absent. PMNs lacking IPSP input nevertheless exhibit vigorous cyclical bursts of action potentials driven by electrical EPSPs. The IPSP of PMNs showed partial or full restoration after 14--32 days of culture despite the lack of reinnervation of normal targets. Existing electrical synapses were apparently more stable during culture, but electrical connections between cyberchrons and PMNs were strengthened. Probably because of the reinforcement of these electrical synapses, regenerative cycles of activity in both cyberchrons and PMNs may often be initiated by brief stimulating of a single PMN in cultured ganglia. This is in marked contrast to normal ganglia in which PMNs possess a limited ability to generate such activity. It is concluded that isolation of the buccal ganglia results in a predictable, functional alteration of its neuronal circuitry. Such a perturbation of connectivity indicates that a significant degree of plasticity can be exhibited by adult molluscan neurons.

Action Potentials↗
PubMed1983

Local interneurons associated with the mushroom bodies and the central body in the brain of Acheta domesticus.

Within the central part of the brain in male crickets (Acheta domesticus) 150 local interneurons were recorded intracellularly and consequently stained with either Lucifer Yellow CH or cobaltous sulphide. The shapes of the injected cells were reconstructed from serial sections and drawn to scale using known brain regions as landmarks. Several types of neurons were encountered, which differ in their topographical relationships to the mushroom bodies and the central body. Extensive branching was often found in the calyces or the lobes of the mushroom bodies, within the lateral protocerebral neuropil and in the columns of the central body. These neurons connect different parts of the brain with the neuronal assemblies of the mushroom bodies and the central body, structures, which are considered to participate in the control of complex behavior. The role of the mushroom body with respect to its connectivity to other brain areas and various feedback loops is discussed.

Animals↗
PubMed2005

Feedback loops link odor and pheromone signaling with reproduction.

Pheromones can have profound effects on reproductive physiology and behavior in mammals. To investigate the neural circuits underlying these effects, we used a genetic transneuronal tracer to identify neurons that synapse with GnRH (LHRH) neurons, the key regulators of reproduction. We then asked whether the connected neurons are presynaptic or postsynaptic to GnRH neurons and analyzed their responses to chemosensory cues. Surprisingly, these experiments indicate that GnRH neurons receive pheromone signals from both odor and pheromone relays in the brain and may also receive common odor signals. Moreover, feedback loops are evident whereby GnRH neurons could influence both odor and pheromone processing. Remarkably, approximately 800 GnRH neurons communicate with approximately 50,000 neurons in 53 functionally diverse brain areas, with some connections exhibiting sexual dimorphism. These studies reveal a complex interplay between reproduction and other functions in which GnRH neurons appear to integrate information from multiple sources and modulate a variety of brain functions.

Amygdala↗
PubMed2003

Connections between respiratory neurones in the neonatal rat transverse medullary slice studied with cross-correlation.

In the transverse medullary slice prepared from neonatal rats the hypoglossal nerve rootlets exhibit a bursting 'respiratory' rhythm as do neurones in the pre-Bötzinger complex (PBC). We used cross-correlation analysis of the rhythmic multiunit discharges recorded from hypoglossal nerve rootlets, hypoglossal nucleus neurones and PBC neurones to investigate the connections between these groups. All cross-correlograms computed between left and right hypoglossal nerves, and between hypoglossal neurones and contralateral hypoglossal nerves, displayed central peaks with broad half-amplitude widths (mean +/- S.D. of 29.6 +/- 10.4 and 37.3 +/- 6.0 ms, respectively), which we interpreted as evidence for activation from a common source. Five of the 18 cross-correlograms computed between left and right PBC neurones displayed peaks either side of time zero with narrower half-amplitude widths (mean +/- S.D. of 9.3 +/- 1.9 ms) superimposed on broader central peaks, which we interpreted as evidence for mutual excitation and common activation, respectively. Cross-correlograms computed between PBC neurones and contralateral hypoglossal neurones or nerves did not display consistent features, but some of those computed between PBC and ipsilateral hypoglossal neurones (two of eight) or nerves (two of five) displayed peaks with broad half-amplitude widths (mean +/- S.D. of 36.8 +/- 6.9 ms), offset from time zero by 6 ms (except for one at 18 ms), which we interpreted as evidence for excitation of hypoglossal neurones and motoneurones by PBC neurones. We concluded that rhythm is synchronised between left and right sides by mutual excitatory connections between left and right PBC neurones. The rhythm is transmitted to ipsilateral hypoglossal neurones by a paucisynaptic pathway. Both hypoglossal neurones and PBC neurones receive a common activation from as yet unidentified sources.

Animals↗
PubMed1990

Requirement for subplate neurons in the formation of thalamocortical connections.

The neurons of layer 4 in the adult cerebral cortex receive their major ascending inputs from the thalamus. In development, however, thalamic axons arrive at the appropriate cortical area long before their target layer 4 neurons have migrated into the cortical plate. The axons accumulate and wait in the zone below the cortical plate, the subplate, for several weeks before invading the cortical plate. The subplate is a transient zone that contains the first postmitotic neurons of the telencephalon. These neurons mature well before other cortical neurons, and disappear by cell death after the thalamic axons have grown into the overlying cortical plate. The close proximity of growing thalamocortical axons and subplate neurons suggests that they might be involved in interactions important for normal thalamocortical development. Here we show that early in development the deletion of subplate neurons located beneath visual cortex prevents axons from the lateral geniculate nucleus of the thalamus from recognizing and innervating visual cortex, their normal target. In the absence of subplate neurons, lateral geniculate nucleus axons continue to grow in the white matter past visual cortex despite the presence of their target layer 4 neurons. Thus the transient subplate neurons are necessary for appropriate cortical target selection by thalamocortical axons.

Animals↗
PubMed1999

The statistical relationship between connectivity and neural activity in fractionally connected feed-forward networks.

It is desirable to have a statistical description of neuronal connectivity in developing tractable theories on the development of biological neural networks and in designing artificial neural networks. In this paper, we bring out a relationship between the statistics of the input environment, the degree of network connectivity, and the average postsynaptic activity. These relationships are derived using simple neurons whose inputs are only feed-forward, excitatory and whose activity is a linear function of its inputs. In particular, we show that only the empirical mean of the pairwise input correlations, rather than the full matrix of all such correlations, is needed to produce an accurate estimate of the number of inputs necessary to attain a prespecified average postsynaptic activity level. Predictions from this work also include distributional aspects of connectivity and activity as shown by a combination of analysis and simulations.

Computer Simulation↗
PubMed1990

The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones.

The study of synaptic connections in the electron microscope has established an 'elementary' circuit for the neostriatum which consists of a pathway from cortical areas (neocortex, hippocampus, amygdala) to medium spiny neurones of the striatum that also receive converging synaptic input from midbrain dopamine neurones. The striatal medium spiny neurones are projection neurones and they form synaptic contacts with output neurones in the globus pallidus and substantia nigra reticulata. In this way, dopaminergic afferents can directly modulate the flow of information from cortical areas through the striatum to the 'premotor' areas of the brainstem and to the thalamus. It is proposed that certain parts of the striatum can themselves control the activity of midbrain dopamine neurones and so one part of the striatum can 'gate' the flow of information through another part.

Animals↗
PubMed2005

New developments in tracing neural circuits with herpesviruses.

Certain neurotropic viruses can invade the nervous system of their hosts and spread in chains of synaptically connected neurons. Consequently, it is possible to identify entire hierarchically connected circuits within an animal. In this review, we discuss the use of neurotropic herpesviruses as neuronal tract tracers. Although a variety of tract tracing viruses are available, each with its own unique infection characteristics, we focus on the widespread use of attenuated strains of pseudorabies virus (PRV), a swine herpesvirus with a broad host range. In particular, we focus on new applications of PRV for tract tracing including use of multiple infections by PRV reporter viruses to test for circuit convergence/divergence within the same animal. We provide examples of these combined application techniques within the context of an animal model to study the naturally occurring reversal of seasonal obesity in Siberian hamsters.

Animals↗