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PubMed2001

Functional connections between the HVC and the shelf of the zebra finch revealed by real-time optical imaging technique.

Auditory-motor interaction is essential for the understanding of avian song learning and maintenance. The HVC is thought to be the most important station for auditory-motor integration in the avian song system. However, little is known about where and how auditory inputs are conveyed into the HVC. The shelf, a multi-auditory recipient region located along the ventral border of the HVC, is thought to be a possible source of auditory inputs to the HVC. Here, we investigated the functional neural connections between the HVC and surrounding area of the HVC including the shelf in zebra finch brain slices, using the real-time optical recording technique. Unexpectedly electrical stimulation of the shelf region did not induce signal propagation into the HVC, but stimulation within the HVC propagated strong signals into the shelf. These results suggest that the shelf is the region that receives output signals from the HVC, rather than a major source of auditory inputs to the HVC.

2-Amino-5-phosphonovalerate↗

PubMed2004

New approaches for exploring anatomical and functional connectivity in the human brain.

Information processing in the primate brain is based on the complementary principles of modular and distributed information processing. The former emphasizes the specialization of functions within different brain areas. The latter emphasizes the massively parallel nature of brain networks and the fact that function also emerges from the flow of information between brain areas. The localization of function to specific brain areas ("functional segregation") is the commonest approach to investigating function; however, an emerging, complementary approach ("functional integration") describes function in terms of the information flow across networks of areas. Here, we highlight recent advances in neuroimaging methodology that have made it possible to investigate the anatomical architecture of networks in the living human brain with diffusion tensor imaging (DTI). We also highlight recent thinking on the ways in which functional imaging can be used to characterize information transmission across networks in the human brain (functional and effective connectivity).

Animals↗

PubMed2026

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50 aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT×diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F = 4.322, P = 0.041); this interaction was driven by CCT specifically in aMCI (F = 4.465, P = 0.038). Significant CCT×diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F = 5.429, P = 0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F = 6.587, P = 0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F = 6.550, P = 0.013; F = 7.097, P = 0.010). No significant interaction effect on the change in hippocampal GMV was noted (P > 0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans↗

PubMed2006

Synaptic plasticity in the adult spinal dorsal horn: the appearance of new functional connections following peripheral nerve regeneration.

Peripherally regenerated fibers were impaled in the dorsal columns. Each impaled fiber's adequate stimulus was determined and the fiber was activated by passing brief (200 ms) current pulses through the microelectrode. Cord dorsum potentials (CDPs) elicited by fiber stimulation were recorded at 8 sites, and then the fiber was injected with Neurobiotin (NB). In the same preparations, dorsal horn cells were impaled and their receptive fields (RFs) mapped; areas of skin from which the most vigorous responses were elicited were noted. Needle electrodes inserted into these cutaneous "hot spots" were used to electrically activate minimal numbers of peripherally regenerated fibers while simultaneously recording the resulting CDPs and any intracellular EPSPs. This allowed determination of connectivity between regenerated fibers and dorsal horn cells with overlapping RFs. In agreement with findings in intact animals, NB revealed long-ranging collaterals which were not seen using intraaxonally injected horseradish peroxidase (HRP). Although there was no qualitative difference in their morphology compared to those seen in controls, the correlation between spatial distribution of boutons and amplitudes of the monosynaptic CDPs of peripherally regenerated fibers revealed significant shifts in the functional efficacy of many central connections. Transcutaneous electrical stimulation revealed a significantly higher incidence of connectivity between regenerated fibers and cells with overlapping RFs at 9-12 months (86%) than at 5-6 months (34%). Although there was no obvious anatomical reorganization of afferent projections in the dorsal horn, the observed functional changes with time following transection show the formation of new functional central connections.

Afferent Pathways↗

PubMed1999

Crossed cerebellar diaschisis: the role of motor and premotor areas in functional connections.

The authors assessed the relationship between crossed cerebellar diaschisis (CCD) and cortico-pontine cerebellar pathway (CPCP) damage in 29 chronic supratentorial infarct patients to elucidate the role of motor and premotor areas for functional cerebro-cerebellar connections. The CCD rate was calculated from side-to-side cerebellar count differences on 123I-IMP single-photon emission computerized tomography images. Neuronal damage was estimated by the three scores of computed tomography density from equal to normal brain tissue (score 0) to equal to cerebrospinal fluid (score 2) in the 4 major regions on CPCP; frontal association, motor and premotor, sensory and parietal associations, and the posterior limb of the internal capsule. Two-factor factorial ANOVA by the score and the region revealed significant differences of the CCD rate in the score factor (score 0 or 1 vs. score 2, p = < 0.05) and the independency of these two factors. Categories determined by the scores in each region were analyzed by multiple stepwise regression analysis using the theory of quantification I, in which significant correlation only between CCD and the necrotic density (score 2) in motor and premotor areas were demonstrated (r = 0.515, p = < 0.05). The authors conclude that neuronal loss in motor and premotor areas seem to contribute significantly to functional cerebro-cerebellar disconnections.

Adult↗

PubMed1991

Comparison of the sequences of the nagE operons from Klebsiella pneumoniae and Escherichia coli K12: enhanced variability of the enzyme IIN-acetylglucosamine in regions connecting functional domains.

The nagE operon, encoding the enzyme II specific for N-acetylglucosamine (EIINag), and adjacent DNA from the chromosome of Klebsiella pneumoniae were sequenced and compared with the corresponding sequence from Escherichia coli K12. The deduced EIINag sequences differ in 72 out of 651 amino acids, the K. pneumoniae sequence being three residues longer. The amino acid differences were distributed unevenly, and were most frequent in regions connecting the three functional domains of the protein. In the nagE-nagB intergenic region, two promoter, two operator, and one CAP consensus sequence with regulatory functions were highly conserved. The nag structural genes from both species were very similar (83% DNA similarity; 89% amino acid similarity) except for frequent AT to GC exchanges in the wobble base of codons in K. pneumoniae DNA relative to the E. coli DNA.

Amino Acid Sequence↗

PubMed2000

Functional connections are established in the deafferented rat spinal cord by peripherally transplanted human embryonic sensory neurons.

Functionally useful repair of the mature spinal cord following injury requires axon growth and the re-establishment of specific synaptic connections. We have shown previously that axons from peripherally grafted human embryonic dorsal root ganglion cells grow for long distances in adult host rat dorsal roots, traverse the interface between the peripheral and central nervous system, and enter the spinal cord to arborize in the dorsal horn. Here we show that these transplants mediate synaptic activity in the host spinal cord. Dorsal root ganglia from human embryonic donors were transplanted in place of native adult rat ganglia. Two to three months after transplantation the recipient rats were examined anatomically and physiologically. Human fibres labelled with a human-specific axon marker were distributed in superficial as well as deep laminae of the recipient rat spinal cord. About 36% of the grafted neurons were double labelled following injections of the fluorescent tracers MiniRuby into the sciatic and Fluoro-Gold into the lower lumbar spinal cord, indicating that some of the grafted neurons had grown processes into the spinal cord as well as towards the denervated peripheral targets. Electrophysiological recordings demonstrated that the transplanted human dorsal roots conducted impulses that evoked postsynaptic activity in dorsal horn neurons and polysynaptic reflexes in ipsilateral ventral roots. The time course of the synaptic activation indicated that the human fibres were non-myelinated or thinly myelinated. Our findings show that growing human sensory nerve fibres which enter the adult deafferentated rat spinal cord become anatomically and physiologically integrated into functional spinal circuits.

Action Potentials↗

PubMed2005

Estimating brain functional connectivity with sparse multivariate autoregression.

There is much current interest in identifying the anatomical and functional circuits that are the basis of the brain's computations, with hope that functional neuroimaging techniques will allow the in vivo study of these neural processes through the statistical analysis of the time-series they produce. Ideally, the use of techniques such as multivariate autoregressive (MAR) modelling should allow the identification of effective connectivity by combining graphical modelling methods with the concept of Granger causality. Unfortunately, current time-series methods perform well only for the case that the length of the time-series Nt is much larger than p, the number of brain sites studied, which is exactly the reverse of the situation in neuroimaging for which relatively short time-series are measured over thousands of voxels. Methods are introduced for dealing with this situation by using sparse MAR models. These can be estimated in a two-stage process involving (i) penalized regression and (ii) pruning of unlikely connections by means of the local false discovery rate developed by Efron. Extensive simulations were performed with idealized cortical networks having small world topologies and stable dynamics. These show that the detection efficiency of connections of the proposed procedure is quite high. Application of the method to real data was illustrated by the identification of neural circuitry related to emotional processing as measured by BOLD.

Brain↗

PubMed2005

Shared brain areas but not functional connections controlling movement timing and order.

Virtually every aspect of the enormous repertoire of human behaviors is embedded in a sequential context, but brain mechanisms underlying the adjustment of two fundamental dimensions defining a motor sequence (order of a series of movements and intervals separating them) as a function of a given goal are poorly understood. Using functional magnetic resonance imaging, we demonstrate that, at the neuronal level, these tasks can only be distinguished by differences in functional interactions between associative areas of common activation, which included bilateral subcortico-parieto-frontal regions, and two subcortical structures. Activity in these shared associative areas was preferentially coupled with that in right putamen during manipulation of timing and with that in right posterior cerebellum during manipulation of serial order. This finding is important because it provides evidence for an efficient organization of the brain during cognitive control of motor sequences and supports a recently proposed principle according to which the role of brain regions involved in different behavioral tasks without differential alterations in their measured activity depends on changes in their interactions with other connected areas as a function of the tasks.

Adult↗

PubMed1996

Functional connectivity between tRNA binding domains in glutaminyl-tRNA synthetase.

The structure of Escherichia coli glutaminyl-tRNA synthetase (GlnRS) in complex with tRNAGln and ATP has identified a number a sequence-specific protein-tRNA interactions. The contribution to glutamine identity has previously been determined for the nucleotides in tRNAGln. Here, we report the mutational analysis of residues in all three tRNA recognition domains of GlnRS, thus completing a survey of the major sequence-specific contacts between GlnRS and tRNAGln. Specifically, we analyzed the GlnRS determinants involved in recognition of the anticodon which is essential for glutamine identity and in the communication of anticodon recognition to the acceptor binding domain in GlnRS. A combined in vivo and in vitro approach has demonstrated that Arg341, which makes a single sequence-specific hydrogen bond with U35 in the anticodon of tRNAGln, is involved in initial RNA recognition and is an important positive determinant for this base in both cognate and non- cognate tRNA contexts. However, Arg341, as well as Arg402, which interacts with G36 in the anticodon, are negative determinants for non-cognate nucleotides at their respective positions. Analysis of acceptor-anticodon binding double mutants and of a mutation of Glu323 in the loop-strand-helix connectivity subdomain in GlnRS has further implicated this domain in the functional communication of anticodon recognition. The better than expected activity (anticooperativity) of these double mutants has led us to propose an "anticodon-independent" mechanism, in which the removal of certain synthetase interactions with the anticodon eliminates structural constraints, thus allowing the relaxed specificity mutants in the acceptor binding domain ot make more productive interactions.

Amino Acyl-tRNA Synthetases↗

PubMedDate not supplied

A functional connection between RanGTP, NF-kappaB and septic shock.

RanGTPase is importantly involved in diverse biological functions, such as nuclear transport, spindle formation during mitosis, DNA replication and cell division. This review summarizes yet another new role of Ran - control of the activity of NF-kappaB in host immune responses. Overexpression of a specific allele of Ran results in preferential accumulation of nuclear RanGTP, downmodulation of proinflammatroy cytokine production and protection against septic shock. Nuclear RanGTP interacts with Exportin1, which in turn binds to IkappaB. Nuclear IkappaB binds to NF-kappaB in the nucleus, inhibiting NF-kappaB transcriptional activation of proinflammatory cytokine genes. Nuclear IkB also functions as an adaptor between NF-kappaB and Exportin1/RanGTP, enhancing export of NF-kappaB to the cytoplasm and further reducing the magnitude of host immune responses. From this picture, it appears that modulation of host immune responses via RanGTPase will have an immense impact on a wide spectrum of emerging infectious diseases, cancer and other genetic diseases.

Animals↗

PubMedDate not supplied

[The character of functional connections in the endocrine system of female white rats and their transformation with age].

The authors studied the functional interrelations between the adrenal glands and the thyroid gland of female albino rats of various age groups. Blood content of 11-oxycorticosteroids and protein-bound iodine was determined. Analogous determinations were carried out in partial exclusion of the adrenal gland function (metapyron block) and of the thyroid gland function (6-methyluracil block). It is supposed that in the young sexually-mature female albino rats the functions of the adrenal glands and the thyroid gland were in direct relationship irrespective of the cyclic variations in the sex steroid secretion; with the advance of age this association became deranged.

11-Hydroxycorticosteroids↗

PubMed1993

Ultrastructural and functional connectivity of intracellularly stained neurones in the vertebrate retina: correlative analyses.

A variety of intracellular recording and staining techniques has been used to establish structure-function and, in some cases, structure-function-neurochemical correlations in fish, turtle, and cat retinae. Cone photoreceptor-horizontal cell connectivity has been studied extensively in the cyprinid fish retina by intracellular staining with horseradish peroxidase (HRP) and subsequent electron microscopy. The available data suggest that horizontal cell dendrites around the ridge of the synaptic ribbon are postsynaptic, whilst finger-like extensions ("spinules") of lateral dendrites function as inhibitory feedback terminals. An interesting feature of this interaction is its plasticity: the feedback pathway is suppressed in the dark and becomes potentiated by light adaptation of the retina. Intracellular recordings and stainings of ganglion cells in both turtle and cat retinae have been possible. Prelabelling of ganglion cells by retrograde transport of rhodamine from the tectum allows ganglion cells to be stained under visual control, and their synaptic inputs determined by electron microscopy. Such studies have been extended to double labelling by using autoradiography or postembedding immunohistochemistry to identify the neurotransmitter content of the labelled cell and/or the neurotransmitter(s) converging upon it. It is envisaged that further applications of intracellular staining followed by double- or even triple-labelling will continue to enhance greatly our understanding of the functional architecture of the vertebrate retina.

Animals↗

PubMed2000

Development of functional connections between thalamic fibres and the visual cortex of the wallaby revealed by current source density analysis in vivo.

Functional development of thalamic input to the cortex in anaesthetised wallaby pouch young between postnatal day 25 (P25) and P153 has been studied by electrical stimulation of the optic nerve, current source density (CSD) analysis, and histologic identification of recording sites. Conduction in the optic nerve was recorded prior to P39, by which time responses from the superior colliculus appeared. No evoked potential of cortical origin was recorded until P46, even though thalamic fibres grew into the cortical plate from P15. The first cortical synaptic responses were recorded at the margin of the subplate and the developing cortical plate, where cells that later comprise the adult layer 6 settle. At about P66, an additional short-latency, superficial response appeared, coinciding with the formation of layer 4. The deep response was retained in layer 6. Evoked activity in the presumed layer 4 was found progressively deeper in the cortex over the next few weeks, which would be expected from the addition of layer 3 above it. By P113, a new sink was added superficial in the cortex. Thalamocortical connections follow the same deep-to-superficial order in development as the cellular layers of the cortex.

Animals↗

PubMed1994

Persisting functional connection in growth-hormone-deficient patients with a transected stalk.

Prolactin response after domperidone (DOM) stimulus was used to investigate the functional status of the hypothalamo-hypophyseal axis in 57 congenital growth-hormone-deficient (GHD) children with and without magnetic resonance imaging (MRI) abnormalities. Response to DOM was significantly lower in the GHD children compared with controls, using maximum peak (p < 0.0001), increase (p < 0.0001) or percentage increase (p < 0.05). The lowest values were observed in patients with hypophyseal stalk transection. Thus, the DOM test revealed reduced dopaminergic transmission in GHD subjects, more severe in the transected group, in whom, however, a response to the stimulus was still present. Therefore, it seems that a residual hypothalamo-hypophyseal connection is preserved even if it is not detectable with MRI.

Adolescent↗

PubMed1999

The neurophysiology of sleep and waking: intracerebral connections, functioning and ascending influences of the medulla oblongata.

This paper focuses on the successive historical papers related to medulla oblongata (M.O.) intracerebral connections, its activities and ascending influences regulating sleep waking behavior. The M.O. certainly influences the quantitative and qualitative processes of waking. However, its neurophysiological properties are often concealed by those of the upper-situated brain stem structures. The M.O., particularly the solitary tract nucleus, is involved in sleep-inducing processes. This nucleus seem to act as a deactivating system of the above situated reticular formation, but it also impacts directly on the thalamocortical slow wave and spindle-inducing processes. The M.O. is significantly involved in paradoxical sleep mechanisms. Indeed, the mesopontine executive centers are unable to induce paradoxical sleep without the M.O. Moreover, stimulation of the solitary tract nucleus afferents can induce paradoxical sleep, and the M.O. metabolic functioning is specifically disturbed by paradoxical sleep deprivation. Finally. there seems to be a paradoxical sleep Zeitgeber. Our current knowledge shows that this lowest brain stem level is crucial for sleep waking mechanisms. It will undoubtedly be further highlighted by future electrophysiologial and neurochemical studies.

Animals↗

PubMed2005

Discovery metabolite profiling--forging functional connections between the proteome and metabolome.

Of primary interest for every enzyme is the identification of its physiological substrates. However, the vast structural diversity of endogenous metabolites, coupled with the overlapping activities of numerous enzymes, makes it difficult to deduce the identity of natural substrates for a given enzyme based on in vitro experiments. To address this challenge, we recently introduced an LC-MS based analytical method termed discovery metabolite profiling (DMP) to evaluate the global metabolic effects of enzyme inactivation in vivo. We have applied DMP to study mice lacking the enzyme fatty acid amide hydrolase (FAAH), which degrades the endocannabinoid family of signaling lipids. DMP identified several previously uncharacterized FAAH substrates, including a structurally novel class of brain lipids that represent conjugates of very long chain fatty acids with the amino acid derivative taurine [N-acyl taurines (NATs)]. These findings show that DMP can establish direct connections between the proteome and metabolome and thus offers a powerful strategy to assign physiological functions to enzymes in the post-genomic era.

Amidohydrolases↗

PubMed2000

ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons.

The connections formed between sensory and motor neurons (MNs) play a critical role in the control of motor behavior. During development, the axons of proprioceptive sensory neurons project into the spinal cord and form both direct and indirect connections with MNs. Two ETS transcription factors, ER81 and PEA3, are expressed by developing proprioceptive neurons and MNs, raising the possibility that these genes are involved in the formation of sensory-motor connections. Er81 mutant mice exhibit a severe motor discoordination, yet the specification of MNs and induction of muscle spindles occurs normally. The motor defect in Er81 mutants results from a failure of group Ia proprioceptive afferents to form a discrete termination zone in the ventral spinal cord. As a consequence there is a dramatic reduction in the formation of direct connections between proprioceptive afferents and MNs. ER81 therefore controls a late step in the establishment of functional sensory-motor circuitry in the developing spinal cord.

Animals↗