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PubMed2002

Somatotopic organization of rat thalamocortical slices.

The thalamocortical slice is widely employed for in vitro studies of cortical circuits. This preparation was developed in order to preserve anatomical and functional connectivity between the ventrobasal thalamus and somatosensory (whisker/barrel) cortex of young mice, and thalamocortical slice experiments have contributed significantly to our understanding of the thalamocortical synapse. Cortical somatotopy within thalamocortical slices, however, has not been characterized, and this greatly limits their use in studies that require identification of cortical areas associated with particular regions of the sensory periphery. To address this shortcoming we used electrophysiological recording and neuroanatomical labeling techniques in rats to mark the position of functionally defined whisker barrels, in vivo. We subsequently processed the brains in a plane appropriate for TC slices and characterized the location of somatotopically identified barrels in relation to other aspects of slice topology. We found that barrels associated with the large mobile whiskers occupy a particular location in TC slices, but that there are certain constraints to studying this portion of the barrelfield in vitro.

Animals↗
PubMed1992

Adult Retinofugal Axons Regenerating Through Peripheral Nerve Grafts Can Restore the Light-induced Pupilloconstriction Reflex.

To investigate the ability of mature regenerating retinal axons to form functional connections within central targets, severed axons were guided into the primary visual centres which subserve the pupillary constriction reflex in response to light. The ocular stump of the transected optic nerve of adult rats was connected by means of an autologous peripheral nerve graft with the pretectal region which contains the relay nucleus of pupillary constriction, the olivary pretectal nucleus. This nucleus is efferently connected with preganglionic neurons in the oculomotor nuclear complex which innervates parasympathetically the muscle constrictors of the iris. Six to sixteen weeks after optic nerve transection and peripheral nerve transplantation, brisk responses were observed in the pupils upon illumination of the transplanted eye. Recovery of the pupil responses indicated that retinal neurons used the peripheral nerve 'bridge' to access the pretectum, in which they established synaptic contacts in sufficient density and with appropriate specificity to reconstitute the function of the traumatically interrupted neuronal circuitry.

Journal Article↗
PubMed1985

Electrophysiology of the subfornical organ and its hypothalamic connections--an in-vivo study in the rat.

The connections of the subfornical organ to a defined population of hypothalamic neurons have been explored with extracellular recording methods in the rat. Electrical stimulation in the subfornical organ has a predominantly excitatory action on a majority of oxytocin and vasopressin-secreting neurosecretory neurons in the supraoptic and paraventricular nuclei. Subfornical organ stimulation also enhances the excitability of paraventricular nucleus neurons that project to the median eminence, and to the dorsomedial medulla. These observations provide initial evidence of functional connectivity of subfornical organ neurons with other hypothalamic cells that are engaged in central regulation of pituitary secretions and autonomic activities.

Animals↗
PubMed1980

Distributed processing by visual interneurons of crayfish brain. I. Response characteristics and synaptic interactions.

1. The visual responses and synaptic interactions of a small population of crayfish interneurons are described. 2. The discharge of optic nerve sustaining fibers (tonic on-cells) appears in the brain prior to the onset of the light-evoked discharge of any of the higher order, descending visual interneurons. Direct depolarization of impaled sustaining fibers elicits impulse responses in a large number of descending interneurons. These results indicate that the sustaining fibers provide the visual input to higher order interneurons. 3. Four classes of descending interneurons can be distinguished. All arise in the brain and have axons in the circumesophageal connectives. The response forms vary from tonic to phasic. Two classes of tonic cells are distinguished by response latency and two classes of phasic neurons are distinguished by the rate of response adaptation. The phasic neurons exhibit the most rapid habituation, the largest receptive fields, and the most potent nonvisual inputs. 4. Synaptic interactions are studied by cross-correlation of impulse trains and direct observation of synaptic potentials. About 84% of the cells examined reveal evidence of functional connections to other descending visual interneurons. 5. Cross-correlograms derived from impulses of parallel interneurons exhibit a mean time lage to peak of 6.6 +/- 2.8 ms (SD). The measured delay from EPSP onset to spike onset is 6.0 +/- 4.0 ms. Thus a substantial proportion of the correlogram's time lag to peak is associated with postsynaptic integration time. 6. Direct depolarization of impaled tonic on-cells elicits impulse activity at a fixed delay in other descending interneurons. 7. Synaptic potentials in descending visual interneurons are correlated 1:1 with axon spikes of other descending interneurons. 8. A third of the 80 interactions examined were reciprocal and many cells were implicated in multiple interactions. 9. The results suggest that the descending visual interneurons are organized in a complex network, which can cordinate the discharge of various subpopulations of the ensemble. It is proposed that the coordination of impulses in parallel interneurons may be a mechanism for coding and information transfer in the crayfish nervous system.

Animals↗
PubMed2005

Minireview: the neuroendocrine regulation of puberty: is the time ripe for a systems biology approach?

The initiation of mammalian puberty requires an increase in pulsatile release of GnRH from the hypothalamus. This increase is brought about by coordinated changes in transsynaptic and glial-neuronal communication. As the neuronal and glial excitatory inputs to the GnRH neuronal network increase, the transsynaptic inhibitory tone decreases, leading to the pubertal activation of GnRH secretion. The excitatory neuronal systems most prevalently involved in this process use glutamate and the peptide kisspeptin for neurotransmission/neuromodulation, whereas the most important inhibitory inputs are provided by gamma-aminobutyric acid (GABA)ergic and opiatergic neurons. Glial cells, on the other hand, facilitate GnRH secretion via growth factor-dependent cell-cell signaling. Coordination of this regulatory neuronal-glial network may require a hierarchical arrangement. One level of coordination appears to be provided by a host of unrelated genes encoding proteins required for cell-cell communication. A second, but overlapping, level might be provided by a second tier of genes engaged in specific cell functions required for productive cell-cell interaction. A third and higher level of control involves the transcriptional regulation of these subordinate genes by a handful of upper echelon genes that, operating within the different neuronal and glial subsets required for the initiation of the pubertal process, sustain the functional integration of the network. The existence of functionally connected genes controlling the pubertal process is consistent with the concept that puberty is under genetic control and that the genetic underpinnings of both normal and deranged puberty are polygenic rather than specified by a single gene. The availability of improved high-throughput techniques and computational methods for global analysis of mRNAs and proteins will allow us to not only initiate the systematic identification of the different components of this neuroendocrine network but also to define their functional interactions.

Animals↗
PubMed2005

The role of the prefrontal cortex in the maintenance of verbal working memory: an event-related FMRI analysis.

Neuroimaging studies have been inconclusive in characterizing the role of the prefrontal cortex (PFC) for maintaining increasingly larger amounts of information in working memory (WM). To address this question, the authors collected event-related functional MRI data while participants performed an item-recognition task in which the number of to-be-remembered letters was parametrically modulated. During maintenance of information in WM, the dorsolateral and the ventrolateral PFC exhibited linearly increasing activation in response to increasing WM load. Prefrontal regions could not be distinguished from one another on the basis of load sensitivity, but the dorsolateral PFC had stronger functional connectivity with the parietal and motor cortex than the ventrolateral PFC. These results suggest an increasingly important role for the PFC in actively maintaining information as the amount of that information increases.

Adult↗
PubMed2003

Vascular connections between the receptacle and empty achenes in sunflower (Helianthus annuus L.).

Empty achenes in sunflower, particularly in the centre of the capitulum, may be caused by poor vascularization. This hypothesis was tested by microscopic examination and translocation experiments. Phloem and xylem were identified by fluorescence of aniline-blue-stained callose and autofluorescence, respectively. Vascular strands that extended from the receptacle into empty achenes were regularly found in longitudinal sections. The phloem-mobile probe, carboxyfluorescein, was translocated from the receptacle to the pericarp and the testa of empty achenes. Similarly, (14)CO(2)-derived (14)C-photoassimilates moved into empty achenes. The observations suggest that empty achenes are both structurally and functionally connected with the vascular system of the receptacle. Hence, deficient vascular connections do not prevent seed filling in sunflower.

Flowers↗
PubMed1987

The effect of brain function on coherence patterns in the bipolar EEG.

Studies of the functional organization of the brain based on measurements of coherence in the EEG have, in the past, suffered from a methodological defect which has made interpretation of the results difficult. The effect involved is the use of an active common reference for the recording of the EEG. As a consequence, inferences related to the functional connectivity of brain between the non-referential sites using coherence have probably been wrong. To avoid the problem with the common reference, we have used bipolar derivations of the EEG and used measurements of coherence to reflect synchrony not between individual sites but between regions of the brain. The EEGs in a population of normal volunteers were examined with respect to coherence. Changes in the patterning of coherence were induced by utilizing EEGs from the volunteers during 3 different functional brain states. The first of these was the resting state, the second the verbal motor state and the third, the spatial motor state. The stepwise discriminant analysis method was used to study differences in the patterning of coherences in the 3 states. The results show that the spatial motor state was the most distinct in this regard amongst the 3 states. They results also interpreted as indicating that changes in the patterning of coherence from that in the resting state consisted of both functionally specific and functionally non-specific components.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Lectin binding sites in Paramecium tetraurelia cells. II. Labeling analysis predominantly of non-secretory components.

All the lectin-FITC conjugates tested (ConA, RCA II, WGA) bind to the surface of Paramecium cells. Yet only WGA yields a distinct fluorescent pattern; it contours the basis of cilia and in some cells it brilliantly stains a few neighbouring rows of the regular surface fields in the anterioventral region (a region known to contain extensive fields of linear aggregates of freeze-fracture particles and to be engaged in conjugation). Incubation in vivo with WGA-FITC resulted in the selective labeling of the cytopharyngeal region as well as of the cytoproct. On Lowicryl K4M sections, WGA-gold probes concomitantly labeled disk-shaped vesicles that are assumed in the literature to serve as shuttle vesicles between these two cell regions and, thus, to connect forming and defecating digesting vacuoles (stages DV I and DV IV). On K4M sections WGA-Au stains also most other components of the lysosomal system. Also on K4M sections RCA II-Au labeled the walls of bacteria contained in DV I and II type digesting vacuoles (but not lysosomes identified bona fide by their size and shape and by their frequent vicinity to or continuity with digesting vacuoles). The WGA data largely support previous conclusions on the possible functional connection of all these elements (DV I-IV, smaller lysosomes, disk-shaped vesicles etc.) of the lysosomal system in Paramecium, as proposed by Allen and his group on the basis of other lines of evidence. As shown in the accompanying paper, ConA-FITC stained ghosts (formed after massive trichocyst exocytosis) also abut into DV-like structures. The different results obtained with the three lectins tested reflect the complex sorting machinery contained in the elaborate lysosomal system of a Paramecium cell. In the cytosol, finally, there occurs a particularly intense staining with ConA-gold, applied to Lowicryl sections, that probably represents glycogen-like particles. The same procedure reveals some weak staining of secretory contents and of nuclear structures.

Animals↗
PubMed2002

The oscillatory activity in the Parkinsonian subthalamic nucleus investigated using the macro-electrodes for deep brain stimulation.

OBJECTIVES: To investigate the oscillatory activity in the Parkinsonian subthalamic nucleus using the macro-electrodes for deep brain stimulation. METHODS: During bilateral deep brain stimulating electrode implantation, spontaneous and evoked field potentials were recorded from the subthalamic nucleus (STN) in two patients with Parkinson's disease (PD) during spontaneous resting tremor, passive manipulation of the wrist, and following electrical stimulation of the contralateral STN. RESULTS: Frequency analysis of the STN field potentials recorded during spontaneous resting tremor showed significant coherence with electromyographic activity in the contralateral arm, suggesting a close involvement of the STN in the generation of resting tremor in PD. The STN responded to passive movement of the contralateral wrist, but not to ipsilateral movement. High frequency (100 Hz) electrical stimulation of the STN induced tremor (4 Hz) in both forearms, and also oscillation of the contralateral STN (4 Hz). In contrast, low frequency (5 Hz) stimulation induced contralateral arrhythmic involuntary movement (3 Hz), but without altering the contralateral STN activity. CONCLUSIONS: We propose that the functional connection between the STN and arm muscles is mainly contralateral, but cross talk may occur between bilateral STN via a frequency-dependent pathway.

Animals↗
PubMed1999

Reorganized cerebral metabolic interactions in temporal lobe epilepsy.

Patients with left temporal lobe epilepsy demonstrate language impairments that are not well understood. To explore abnormal patterns of brain functional connections with respect to language processing, we applied a principal component analysis to resting regional cerebral metabolic data obtained with positron emission tomography in patients with right- and left-sided temporal lobe epilepsy and controls. Two principal components were expressed differentially among the groups. One principal component comprised a pattern of metabolic interactions involving left inferior frontal and left superior temporal regions-corresponding to Broca's and Wernicke's areas, respectively-and right mesial temporal cortex and right thalamus. Functional couplings between these brain regions were abnormally enhanced in the left-sided epilepsy patients. The right thalamic left superior temporal coupling was also abnormally enhanced in the right-sided epilepsy patients, but differentially from that in the left-sided patients. The other principal component was characterized by a pattern of metabolic interactions involving right and left mid prefrontal and right superior temporal cortex. Although both the right- and left-sided epilepsy patients showed decreased functional couplings between left mid prefrontal and the other brain regions, a weaker right-left mid prefrontal coupling in the left-sided epilepsy patients best distinguished them from the right-sided patients. The two mutually independent, abnormal metabolic patterns each predicted verbal intelligence deficits in the patients. The findings suggest a site-dependent reorganization of two independent, language-subserving pathways in temporal lobe epilepsy.

Adolescent↗
PubMed1993

[Functional imaging of the brain using low dose gadolinium-DTPA and Turbo-FLASH sequences].

A method for measuring regional blood volume and flow is described based on the reduced relaxation time following intravenous injection of Gd-DTPA. The optimal Gd dose and other parameters were first determined using turbo-flash sequences and a dilution phantom. A single maximum was found for a Gd-DTPA concentration of 4 mmol/l. Taking account of normal heart/time volumes and in order to stay below this arterial value Gd-DTPA was injected as a bolus at the rate of 1 mmol/sec. From the phantom measurements there appears to be a functional connection between measured signal intensity and Gd concentration. The method was applied to 15 patients with cerebral tumours, using altogether 26 perfusion examinations. The results from 4 patients are given as examples; in these, blood volume and flow were calculated for each pixel in a 128 x 128 matrix. It was found that the Gd-DTPA injected is sufficient to be shown with certainty in the grey and white matter and that this is able to demonstrate pathological changes in a functional manner. Comparison with Gd-DTPA doses such as are used for morphological imaging (typically, 10 mmol corresponding to 0.1 mmol/kg body weight) has shown that doses above 1.6 mmol may lead to distortion of the concentration curves.

Aged↗
PubMed2004

Palmitoylation supports assembly and function of integrin-tetraspanin complexes.

As observed previously, tetraspanin palmitoylation promotes tetraspanin microdomain assembly. Here, we show that palmitoylated integrins (alpha3, alpha6, and beta4 subunits) and tetraspanins (CD9, CD81, and CD63) coexist in substantially overlapping complexes. Removal of beta4 palmitoylation sites markedly impaired cell spreading and signaling through p130Cas on laminin substrate. Also in palmitoylation-deficient beta4, secondary associations with tetraspanins (CD9, CD81, and CD63) were diminished and cell surface CD9 clustering was decreased, whereas core alpha6beta4-CD151 complex formation was unaltered. There is also a functional connection between CD9 and beta4 integrins, as evidenced by anti-CD9 antibody effects on beta4-dependent cell spreading. Notably, beta4 palmitoylation neither increased localization into "light membrane" fractions of sucrose gradients nor decreased solubility in nonionic detergents-hence it does not promote lipid raft association. Instead, palmitoylation of beta4 (and of the closely associated tetraspanin CD151) promotes CD151-alpha6beta4 incorporation into a network of secondary tetraspanin interactions (with CD9, CD81, CD63, etc.), which provides a novel framework for functional regulation.

Animals↗
PubMed2004

Comparative study of the heterophil phagocytic function in young and old ring doves (Streptopelia risoria) and its relationship with melatonin levels.

A functional connection between the pineal gland (via the hormone melatonin) and the immune system has been suggested. In our previous results in the ring dove, we observed diurnal oscillations in the levels of this neurohormone in young animals and a decline in its plasma levels with advancing age (which is accompanied by the absence of diurnal rhythm). We also noted enhanced phagocytic activity of heterophils from old animals after in vitro incubation with both physiological and pharmacological doses of melatonin. Here, we evaluate the functional capacity of ring dove (Streptopelia risoria) heterophils in young (2 years of age) and old (8 years and more) animals at different times of day (0:00, 10:00 and 16:00, the times when the maximum, minimum, and mean values, respectively, of melatonin levels are observed in young animals). The phagocytic capacities for the ingestion of latex beads and Candida albicans were evaluated, as well as the oxidative metabolism which accompanies phagocytosis. At all three times of day studied, the heterophil phagocytic function with both latex and C. albicans was significantly greater in the young than in the old animals, and in the young animal cells it was significantly higher at 0:00. In addition, in the presence of latex beads, there was a significant decline at 10:00 and 0:00 of superoxide anion levels in the young animals relative to the old. In the young animals, there was a decline at 0:00 in comparison with both 10:00 and 16:00, and in the old animals there was a decline at both 0:00 and 16:00 compared with 10:00. These results could be due, at least in part, to the absence of a diurnal rhythm of melatonin in old animals, and to an enhancing effect of that hormone on young animals' heterophil phagocytic function, which would also neutralize the oxidative stress deriving from this immune function.

Age Factors↗
PubMed2006

Children and adolescents with autism exhibit reduced MEG steady-state gamma responses.

BACKGROUND: Recent neuroimaging studies of autism have indicated reduced functional connectivity during both cognitive tasks and rest. These data suggest long-range connectivity may be compromised in this disorder, and current neurological theories of autism contend disrupted inter-regional interactions may be an underlying mechanism explaining behavioral symptomatology. However, it is unclear whether deficient neuronal communication is attributable to fewer long-range tracts or more of a local deficit in neural circuitry. This study examines the integrity of local circuitry by focusing on gamma band activity in auditory cortices of children and adolescents with autism. METHODS: Ten children and adolescents with autism and 10 matched controls participated. Both groups listened to 500 ms duration monaural click trains with a 25 ms inter-click interval, as magnetoencephalography was acquired from the contralateral hemisphere. To estimate 40 Hz spectral power density, we performed time-frequency decomposition of the single-trial magnetic steady-state response data using complex demodulation. RESULTS: Children and adolescents with autism exhibited significantly reduced left hemispheric 40 Hz power from 200-500 ms post-stimulus onset. In contrast, no significant between group differences were observed for right hemispheric cortices. CONCLUSIONS: The production and/or maintenance of left hemispheric gamma oscillations appeared abnormal in participants with autism. We interpret these data as indicating that in autism, particular brain regions may be unable to generate the high-frequency activity likely necessary for binding and other forms of inter-regional interactions. These findings augment connectivity theories of autism with novel evidence that aberrations in local circuitry could underlie putative deficiencies in long-range neural communication.

Acoustic Stimulation↗
PubMed2006

Network analysis of single-subject fMRI during a finger opposition task.

The analysis of functional magnetic resonance imaging (fMRI) data has typically relied on univariate methods to identify areas of brain activity related to cognitive and behavioral task performance. We investigated the ability of multivariate network analysis using a modified form of principal component analysis, the Scaled Subprofile Model (SSM), applied to single-subject fMRI data to identify patterns of interactions among brain regions over time during an anatomically well-characterized simple motor task. We hypothesized that each subject would exhibit correlated patterns of brain activation in several regions known to participate in the regulation of movement including the contralateral motor cortex and the ipsilateral cerebellum. EPI BOLD images were acquired in six healthy participants as they performed a visually and auditorally paced finger opposition task. SSM analysis was applied to the fMR time series on a single-subject basis. Linear combinations of the major principal components that predicted the expected hemodynamic response to the order of experimental conditions were identified for each participant. These combinations of SSM patterns were highly associated with the expected hemodynamic response, an indicator of local neuronal activity, in each participant (0.84 </= R(2) </= 0.97, all P's < 0.0001). As predicted, the combined pattern in each subject was characterized most prominently by relatively increased activations in contralateral sensorimotor cortex and ipsilateral cerebellum. Additionally, all subjects showed areas of relatively decreased activation in the ipsilateral sensorimotor cortex and contralateral cerebellum. The application of network analysis methods, such as SSM, to single-subject fMRI data can identify patterns of task-specific, functionally interacting brain areas in individual subjects. This approach may help identify individual differences in the task-related functional connectivity, track changes in task-related patterns of activity within or between fMRI sessions, and provide a method to identify individual differences in response to treatment.

Acoustic Stimulation↗
PubMed1982

Potentiation of phenobarbital-induced anticonvulsant activity by pipecolic acid.

Pipecolic acid (PA) is an intermediate of lysine metabolism in the mammalian brain. Recent findings suggest a functional connection of PA as neuromodulator in GABAergic transmission. Since many drugs are postulated to produce their effects by interaction with the central GABA system, the influence of PA on the anticonvulsant activity of phenobarbital was examined. Pretreatment of mice with 50 mg . kg-1 of PA potentiated the suppressing effects of the barbiturate on electrically and chemically induced convulsions. However, there was no potentiation of the behavioral effects and hypothermia induced by phenobarbital. PA itself had no or only little effect on the convulsions, motor function and rectal temperature when given in i.p. doses up to 500 mg . kg-1. Intraventricular administration of 500 microgram of PA also did not suppress either type of convulsion, although it produced ptosis, hypotonia, sedation and hypothermia. The results are discussed in relation to GABA system.

Animals↗
PubMed1988

Mechanisms of mania after brain injury. 12 case reports and review of the literature.

Twelve patients who developed mania after a brain lesion are reported. Ages ranged from 20 to 83 years. Five patients had brain tumors (three frontal meningiomas, one temporal meningioma, and one temporal astrocytoma), four patients had stroke lesions (one frontal, one temporal, and two thalamocapsular), two patients had a traumatic frontal closed head injury, and one patient had a pituitary adenoma resection. Although seven patients had lesions restricted to the right hemisphere, four had bilateral or midline damage and one had a left hemisphere lesion. Damage to structures functionally connected to the obitofrontal cortex, mainly in the right hemisphere, seems to be associated with secondary mania. The possible roles of monoaminergic, genetic, and perinatal factors in the pathogenesis of secondary mania are discussed.

Adult↗