Local-density approximation, hierarchy of equations, functional expansion, and adiabatic connection in current-density-functional theory.
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Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury.
Chronic impairment of forelimb and digit movement is a common problem after stroke that is resistant to therapy. Previous studies have demonstrated that enrichment improves behavioral outcome after focal ischemia; however, postischemic enrichment alone is not capable of enhancing fine digit and forelimb function. Therefore, we combined environmental enrichment with daily skilled-reach training to assess the effect of intensive task-specific rehabilitation on long-term functional outcome. Rats were subjected to either endothelin-1-induced focal ischemia or sham surgery and subsequently designated to enriched-rehabilitation or standard-housing treatment groups starting 15 d after ischemia. Functional assessment of the affected forelimb at 4 and 9 weeks after treatment revealed that ischemic plus enrichment (IE) animals had improved approximately 30% on the staircase-reaching task and were indistinguishable from sham animals for both latency and foot faults in a beam-traversing task. In contrast, ischemic plus standard (IS) animals remained significantly impaired on both tasks. Interestingly, both ischemic groups (IE and IS) relied on the nonaffected forelimb during upright weight-bearing movements, a pattern that persisted for the duration of the experiment. Dendritic arborization of layer V pyramidal cells within the undamaged motor cortex was examined using a Golgi-Cox procedure. IE animals showed enhanced dendritic complexity and length compared with both IS and sham groups. These results suggest that enrichment combined with task-specific rehabilitative therapy is capable of augmenting intrinsic neuronal plasticity within noninjured, functionally connected brain regions, as well as promoting enhanced functional outcome.
Animals↗
Neuroglia in central Wallerian Degeneration (ultrastructural and histoenzymatic studies).
In adult rabbits, unilateral enucleation was performed and morphological changes resulting from disconnection of the axons from their perikaryons of the optic nerve evaluated by means of light and electron microscopy. The morphological changes were compared with histochemically determined activities of several hydrolytic and oxidoreductive enzymes. The results obtained lead to the following conclusions: 1. Astroglial cells displaying increased enzymic activity of many hydrolases and oxidoreductases constitute the main cellular component of the mature optic nerve undergoing Wallerian degeneration. 2. Oligodendroglial cells of the degenerating optic nerve were found as well inside as in their usual position i.e. outside the axons. These cells displayed only slightly expressed morphological or histochemical signs of an increased biological activity. 3. In the mature optic nerve undergoing Wallerian degeneration some signs of remyelination i.e. formation of an aberrant myelin without proper connection to axons, were observed. 4. An intact functional connection between the perikaryons, the axons and myelin sheaths is in the mature optic nerve not indispensable for initiation of myelinogenesis during Wallerian degeneration.
Acid Phosphatase↗
Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts.
Glucocorticoids have important effects on osteoblastic function. Connective tissue growth factor (CTGF)/insulin-like growth factor binding protein-related protein 2 (IGFBP-rP2) plays a role in cell adhesion and function. We examined the regulation of CTGF/IGFBP-rP2 synthesis in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). Cortisol caused a time- and dose-dependent increase in CTGF/IGFBP-rP2 mRNA levels in Ob cells. Cycloheximide did not preclude the effect, indicating that it was not protein synthesis dependent. Cortisol increased the rate of CTGF/IGFBP-rP2 transcription and, in transcriptionally arrested Ob cells, did not modify the decay of the transcript. Parathyroid hormone decreased, whereas transforming growth factor-beta and, to a lesser extent, bone morphogenetic protein 2 increased CTGF/IGFBP-rP2 mRNA levels, but other hormones and growth factors had no effect. In conclusion, cortisol stimulates CTGF/IGFBP-rP2 transcription in Ob cells. Because CTGF/IGFBP-rP2 binds IGFs, its increased expression could be relevant to the actions of cortisol in bone.
Animals↗
Genome-wide transcriptional changes associated with enhanced activity in the Drosophila nervous system.
Neuronal plasticity is an important feature of the developing brain and requires neuronal circuits to reconfigure their functional connectivity depending upon activity patterns. To explore changes in neuronal function that occur downstream of altered activity, we performed an expression analysis in Drosophila mutants with acute or chronic alterations in neuronal activity. We find that seizure induction leads to an overproliferation of synaptic connections, indicating that activity-dependent neuronal rewiring occurs in Drosophila. To analyze transcriptional recoding during altered neuronal activity, we performed genome-wide DNA microarray analysis following multiple seizure induction and recovery paradigms. Approximately 250 genes implicated in cell adhesion, membrane excitability, and cellular signaling are differentially regulated, including the Kek 2 neuronal cell adhesion protein, which, as we demonstrate, functions as a regulator of synaptic growth. These data identify a collection of activity-regulated transcripts that may link changes in neuronal firing patterns to transcription-dependent modulation of brain function, including activity-dependent synaptic rewiring.
Action Potentials↗
CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins.
We report a novel multivalent PDZ domain protein, CIPP (for channel-interacting PDZ domain protein), which is expressed exclusively in brain and kidney. Within the brain, the highest CIPP mRNA levels were found in neurons of the cerebellum, inferior colliculus, vestibular nucleus, facial nucleus, and thalamus. Furthermore, we identified the inward rectifier K+ (Kir) channel, Kir4.1 (also called "Kir1.2"), as a cellular CIPP ligand. Among several other Kir channels tested, only the closely related Kir4.2 (or "Kir1.3") also interacted with CIPP. In addition, specific PDZ domains within CIPP associated selectively with the C-termini of N-methyl-D-aspartate subtypes of glutamate receptors, as well as neurexins and neuroligins, cell surface molecules enriched in synaptic membranes. Thus, CIPP may serve as a scaffold that brings structurally diverse but functionally connected proteins into close proximity at the synapse. The functional consequences of CIPP expression on Kir4.1 channels were studied using whole-cell voltage clamp techniques in Kir4.1 transfected COS-7 cells. On average, Kir4.1 current densities were doubled by cotransfection with CIPP.
Animals↗
Estimation of the cortical connectivity by high-resolution EEG and structural equation modeling: simulations and application to finger tapping data.
Today, the concept of brain connectivity plays a central role in the neuroscience. While functional connectivity is defined as the temporal coherence between the activities of different brain areas, the effective connectivity is defined as the simplest brain circuit that would produce the same temporal relationship as observed experimentally between cortical sites. The most used method to estimate effective connectivity in neuroscience is the structural equation modeling (SEM), typically used on data related to the brain hemodynamic behavior. However, the use of hemodynamic measures limits the temporal resolution on which the brain process can be followed. The present research proposes the use of the SEM approach on the cortical waveforms estimated from the high-resolution EEG data, which exhibits a good spatial resolution and a higher temporal resolution than hemodynamic measures. We performed a simulation study, in which different main factors were systematically manipulated in the generation of test signals, and the errors in the estimated connectivity were evaluated by the analysis of variance (ANOVA). Such factors were the signal-to-noise ratio and the duration of the simulated cortical activity. Since SEM technique is based on the use of a model formulated on the basis of anatomical and physiological constraints, different experimental conditions were analyzed, in order to evaluate the effect of errors made in the a priori model formulation on its performances. The feasibility of the proposed approach has been shown in a human study using high-resolution EEG recordings related to finger tapping movements.
Algorithms↗
[Electrophysiologic study of hippocampo-hypothalamic connections in rabbits].
Using the evoked potentials (EP) studies have been made on functional connections of different fields (CA1, CA3) of the dorsal hippocamp with phylogenetically different parts of the hypothalamus in rabbits. It was shown that during stimulation of both the field CA1 and the field CA3 of the hippocamp, the EP are widely present in nuclear structures of the posterior hypothalamus (supramammilary area, the posterior hypothalamic area, mammilary bodies). In the anterior hypothalamus (area preoptic medialis), the EP were recorded only during stimulation of the field CA1 in the dorsal hippocamp.
Animals↗
Effect of initial fMRI data modeling on the connectivity reported between brain areas.
Nearly all neuroimaging data analysis rests upon some form of variance partitioning. Conventional analyses, with a general linear model (GLM), partition the variance in the measured response variable into partitions described by a design matrix of explanatory variables. This approach can also be adopted in the initial modeling of the data in studies using data-led methods to summarize functional connectivity, such as principle component analysis, or studies of effective connectivity, using for example structural equation modeling. The point made in this technical note is that the partition of the original time series has to be precisely described to qualify the sources of variations that are taken into account. For conventional analyses using the GLM, the partition investigated corresponds to the subspaces of the design matrix that are tested. However, in the analyses of functional and effective connectivity, the particular subspaces considered are not always specified explicitly. Here we show that selecting different subspaces, or variance partitions, can have a profound effect, both qualitatively and quantitatively, on the sample covariances and the ensuing inferences about connectivity. We will illustrate this using simulated data that include condition and block-related effects and their interactions. We will use these three subspaces to show how the correlation between two voxels depends on which sub-partitions are examined. We will also show how the partition of the design matrix influences the resulting correlation matrix observed when studying correlations between error terms. We will finally demonstrate, quantitatively, the effect of the variance partitions considered on the correlations between two regions using a real fMRI study of biological motion.
Brain↗
Sleep function.
A theory of sleep function and brain organization positing that sleep serves a neuronal connectivity function and is a fundamental property of highly interconnected groups of neurons (neuronal groups) is presented. Cellular electrical activity within neuronal groups leads to the production of sleep-promoting substances which are also cytokine growth factors. The somnogenic cytokine growth factors (SCGF) in turn, induce molecules necessary for synaptic connectivity. The SCGFs change the synaptic activation patterns within neuronal groups. SCGFs thus induce changes in the input-output relationships of neuronal groups and thereby, cause a neuronal group state shift. Altered input-output relations result in increased efficacy of some synapses. Sleep is thus, targeted to active neuronal groups and serves to incorporate novel stimulus patterns into a synaptic contextual network and also to preserve that network. Coordination of neuronal group state is brought about by sleep regulatory networks. Organism sleep is an emergent property of a population of neuronal groups in the sleep state. After the neuronal group state shift, environmental input is divorced from output. Sleep is thus, useful to keep the animal stationary at a time when its brain is most dysfunctional. Thus, not only is unconsciousness needed because output activity would be out of phase with environmental events, but it is the consequence of the process itself.
Animals↗
Neural connectivity only accounts for a small part of neural correlation in auditory cortex.
In order to allow the relation of functional connectivity patterns (inferred from cross-correlograms) to structural connectivity (the anatomical substrate), we analyzed cross-correlogram peaks for spontaneous and stimulated activity in the auditory cortex. It was assumed that the broad correlograms, usually encountered, represent neural connectivity as well as secondary effects such as intrinsic firing patterns, global synchrony related to the ongoing electroencephalographic activity, and stimulus-related effects. Data were collected from 604 neuron pairs recorded under spontaneous conditions in primary auditory cortex of seven juvenile (30-70 days) and nine adult cats. Three hundred and six pairs (51%) had a peak cross-correlation coefficient significantly different from zero. For 113 neuron pairs out of this subgroup, correlations were calculated also for spike trains recorded during click stimulation. After a combined burst-correction and deconvolution procedure was carried out, the correlation peak strengths were not significantly changed for spontaneous activity, but peak width was narrower for single-electrode pairs than for dual-electrode pairs, suggesting a better synchronization for neighboring neurons. Under click stimulation conditions, overall peak synchronization strength was independent of interelectrode distance, whereas, after correction for secondary and stimulus effects, peak synchronization was significantly lower for dual-electrode pairs. However, the primary peak width for single-electrode pairs under stimulus conditions was no longer different from that of dual-electrode pairs. This implies that both under spontaneous and stimulus conditions secondary effects largely obscure any underlying correlation produced by anatomical connectivity. The secondary effects may be the result of intrinsic as well as network properties in auditory cortex and may functionally be more important than the weak primary effects resulting from anatomical connections. Cross-interval analysis suggests that the correlations in auditory cortex are dynamic and may show random switching between states of stronger and weaker synchronization.
Acoustic Stimulation↗
[Image processing in the primary visual cortex].
INTRODUCTION: Area 17 or the primary visual area forms the first link in the chain of cerebral analysis of a visual image. The neurones forming the primary visual cortex are characterized by the extreme precision of their connections, functional specialization and hierarchic organization. The spatial precision of the connections within the system for vision permit retinotopic representation in the visual cortex, so that each point of the retina is projected into a specific area of the cortex. The cortical neurones which analyze the characteristics of the image situated in a precise zone of the visual field are themselves organized into a basic functional unit known as a hypercolumn. Within each hypercolumn there are various columnar cell systems with receptive fields having similar characteristics. Thus, each hypercolumn is made up of multiple orientation columns, two ocular dominance columns and 'blob' regions. All these systems permit the analysis of different aspects of the image. The neurones belonging to the orientation columns are sensitive to the orientation, spatial frequency and movement of a visual stimulus; those of the 'blob' regions to colour, and the binocular neurones of the ocular dominance columns to depth. Within each column, the hierarchical pattern of neurone interconnections determines the successive appearance of cells with receptive fields having new properties.
Geniculate Bodies↗
Fine modulation in network activation during motor execution and motor imagery.
Motor imagery, the 'mental rehearsal of motor acts without overt movements', involves either a visual representation (visual imagery, VI) or mental simulation of movement, associated with a kinesthetic feeling (kinetic imagery, KI). Previous brain imaging work suggests that patterns of brain activation differ when comparing execution (E) with either type of imagery but the functional connectivity of the participating networks has not been studied. Using functional magnetic resonance imaging (fMRI) and structural equation modeling, this study elucidates the inter-relationships among the relevant areas for each of the three motor behaviors. Our results suggest that networks underlying these behaviors are not identical, despite the extensive overlap between E and KI. Inputs to M1, which are facilitatory during E, have the opposite effect during KI, suggesting a physiological mechanism whereby the system prevents overt movements. Finally, this study highlights the role of the connection of superior parietal lobule to the supplementary motor area in both types of motor imagery.
Adult↗
Binding sites in Escherichia coli dihydrofolate reductase communicate by modulating the conformational ensemble.
To explore how distal mutations affect binding sites and how binding sites in proteins communicate, an ensemble-based model of the native state was used to define the energetic connectivities between the different structural elements of Escherichia coli dihydrofolate reductase. Analysis of this model protein has allowed us to identify two important aspects of intramolecular communication. First, within a protein, pair-wise couplings exist that define the magnitude and extent to which mutational effects propagate from the point of origin. These pair-wise couplings can be identified from a quantity we define as the residue-specific connectivity. Second, in addition to the pair-wise energetic coupling between residues, there exists functional connectivity, which identifies energetic coupling between entire functional elements (i.e., binding sites) and the rest of the protein. Analysis of the energetic couplings provides access to the thermodynamic domain structure in dihydrofolate reductase as well as the susceptibility of the different regions of the protein to both small-scale (e.g., point mutations) and large-scale perturbations (e. g., binding ligand). The results point toward a view of allosterism and signal transduction wherein perturbations do not necessarily propagate through structure via a series of conformational distortions that extend from one active site to another. Instead, the observed behavior is a manifestation of the distribution of states in the ensemble and how the distribution is affected by the perturbation.
Binding Sites↗
Dynamic temporal properties of effective connections in rat dorsal cochlear nucleus.
In a prior report we presented evidence that functionally connected dorsal cochlear nucleus (DCN) neurons in close proximity can show differing peristimulus time histograms (PSTHs) in response to the same stimulus. We wished to further investigate how interconnections between such neurons might participate in the PSTH patterns. Methodology has recently been developed which permits measurement of rapid changes in effective connectivity between neuron pairs: the normalized joint PSTH. Using this technique we have observed that rapid changes in effective connectivity do occur in the DCN. These observations demonstrate that the effects of one DCN neuron on another cannot necessarily be understood by sequential recordings from single units, even if anatomical connectivity can be established.
Acoustic Stimulation↗
Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose.
Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca's area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern.
Adult↗
The patterns of [14C]2-deoxyglucose uptake in female rat brain produced by electrical stimulation of hypothalamic and limbic brain areas.
The aim of this study was to investigate the pattern of [14C]2-deoxyglucose uptake in anaesthetized rat brain produced by electrical stimulation of brain areas implicated, by previous electrical stimulation studies, in the neural control of pituitary hormone and especially gonadotrophin secretion. Stimulation of the median eminence led to a significant increase in the relative metabolic activities of the arcuate, ventromedial hypothalamic, supraoptic and paraventricular nuclei and the preoptic area. Stimulation of the suprachiasmatic or paraventricular nuclei or the medial preoptic area, anterior hypothalamic area, the dorsal or ventral hippocampus or amygdala led to an increase in the relative metabolic activity of many brain regions known to have direct connections with these areas, but in addition produced increases in the relative metabolic activity of areas which have secondary connections. Hippocampal stimulation confirmed previous neuroanatomical findings of major intrinsic functional connections between different fields of the ipsilateral and contralateral hippocampus. Stimulation of the amygdala, unexpectedly, did not change the relative metabolic activity of the arcuate nucleus and medial preoptic area which have neuroanatomical connections with the amygdala. Similarly, stimulation of the medial preoptic area did not change significantly the relative metabolic activity of the mamillary body and dorsomedial thalamic area. The effect of preoptic area stimulation on the relative metabolic activity of several brain regions was changed by ovariectomy and by injection of oestradiol benzoate. Stimulation of the preoptic area and suprachiasmatic nuclei, but not the anterior hypothalamic area or other brain regions, increased significantly the plasma concentrations of luteinizing hormone. These results show that (i) electrical stimulation of brain areas concerned with the control of gonadotrophin and other pituitary hormone secretion changes the metabolic activity of nuclei and neural pathways extrinsic as well as intrinsic to the hypothalamic-pituitary system, (ii) the [14C]2-deoxyglucose method can detect changes in antidromic as well as orthodromic activity and in multi-synaptic pathways, (iii) neuroanatomical pathways are not always activated metabolically by electrical stimulation, and (iv) the preoptic-suprachiasmatic nucleus gonadotrophin control system is discrete and is little affected by increased metabolic activity of the hypothalamus produced by stimulation of the anterior hypothalamic area or other brain areas.
Animals↗
Modulatory treatment of NMDA receptors in neonatal rats affects cognitive behavior in adult age.
The glutamatergic NMDA receptor is probably involved in establishing functional connections during development, and interference may promote or impair cognitive functions in adult age. In the present study, rat pups received one daily injection of the NMDA receptor partial agonist D-cycloserine in various concentrations (3, 10, 50 mg/kg), the NMDA receptor antagonist (+/-)-HA-966 (30 mg/kg), or saline throughout postnatal days 10-20 (Experiment 1). In Experiment 2, effects of the (+)-enantiomer of HA-966 were similarly examined. The rats were tested in a novelty task in adult age (postnatal days 98-112). The results from Experiment 1 show that injections of D-cycloserine in the concentration of 10 mg/kg or (+/-)-HA-966 caused a slight increase in locomotor activity only. The results from Experiment 2 show that (+)-HA-966-treated rats displayed reduced preference for novelty, a slight reduction in exploratory activity and locomotor behavior, and increased rate of grooming. These results suggest that neonatal treatment with (+)-HA-966 can impair cognitive behavior in adult life. It was not possible to record any effects on cognitive function after neonatal administration of the glutamatergic agonist D-cycloserine.
Animals↗