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At least 1,621 records · Page 90Linked to original sources

PubMed2005

Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress.

Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response.

Adult↗

PubMed2006

Binding crossmodal object features in perirhinal cortex.

Knowledge of objects in the world is stored in our brains as rich, multimodal representations. Because the neural pathways that process this diverse sensory information are largely anatomically distinct, a fundamental challenge to cognitive neuroscience is to explain how the brain binds the different sensory features that comprise an object to form meaningful, multimodal object representations. Studies with nonhuman primates suggest that a structure at the culmination of the object recognition system (the perirhinal cortex) performs this critical function. In contrast, human neuroimaging studies implicate the posterior superior temporal sulcus (pSTS). The results of the functional MRI study reported here resolve this apparent discrepancy by demonstrating that both pSTS and the perirhinal cortex contribute to crossmodal binding in humans, but in different ways. Significantly, only perirhinal cortex activity is modulated by meaning variables (e.g., semantic congruency and semantic category), suggesting that these two regions play complementary functional roles, with pSTS acting as a presemantic, heteromodal region for crossmodal perceptual features, and perirhinal cortex integrating these features into higher-level conceptual representations. This interpretation is supported by the results of our behavioral study: Patients with lesions, including the perirhinal cortex, but not patients with damage restricted to frontal cortex, were impaired on the same crossmodal integration task, and their performance was significantly influenced by the same semantic factors, mirroring the functional MRI findings. These results integrate nonhuman and human primate research by providing converging evidence that human perirhinal cortex is also critically involved in processing meaningful aspects of multimodal object representations.

Adolescent↗

PubMed2003

Adrenergic regulation of clock gene expression in mouse liver.

A main oscillator in the suprachiasmatic nucleus (SCN) conveys circadian information to the peripheral clock systems for the regulation of fundamental physiological functions. Although polysynaptic autonomic neural pathways between the SCN and the liver were observed in rats, whether activation of the sympathetic nervous system entrains clock gene expression in the liver has yet to be understood. To assess sympathetic innervation from the SCN to liver tissue, we investigated whether injection of adrenaline/noradrenaline (epinephrine/norepinephrine) or sympathetic nerve stimulation could induce mPer gene expression in mouse liver. Acute administration of adrenaline or noradrenaline increased mPer1 but not mPer2 expression in the liver of mice in vivo and in hepatic slices in vitro. Electrical stimulation of the sympathetic nerves or adrenaline injection caused an elevation of bioluminescence in the liver area of transgenic mice carrying mPer1 promoter-luciferase. Under a light-dark cycle, destruction of the SCN flattened the daily rhythms of not only mPer1, mPer2, and mBmal1 genes but also noradrenaline content in the liver. Daily injection of adrenaline, administered at a fixed time for 6 days, recovered oscillations of mPer2 and mBmal1 gene expression in the liver of mice with SCN lesion on day 7. Sympathetic nerve denervation by 6-hydroxydopamine flattened the daily rhythm of mPer1 and mPer2 gene expression. Thus, on the basis of the present results, activation of the sympathetic nerves through noradrenaline and/or adrenaline release was a factor controlling the peripheral clock.

Animals↗

PubMed2003

Activity of the Caenorhabditis elegans UNC-86 POU transcription factor modulates olfactory sensitivity.

The activity of transcription factors modulates several neural pathways that mediate complex behaviors. We describe here the role of the POU transcription factor UNC-86 in the olfactory behavior of Caenorhabditis elegans. unc-86-null mutants are defective in response to odor attractants but avoid odor repellents normally. Continuous UNC-86 activity is necessary for maintenance of odortaxis behavior; hyperactivation of UNC-86 by fusion to a VP16 activation domain dramatically enhances sensitivity to odor attractants and promotes odor-attractant adaptation. UNC-86 is not expressed in olfactory sensory neurons but is expressed throughout the life of the animal in the AIZ interneurons of the odorsensory pathway. We suggest that UNC-86 transcriptional activity regulates the expression of genes that mediate synaptic properties of AIZ and that hyperactive UNC-86::VP16 may enhance the expression of synaptic components to affect the capacity to analyze and process sensory information.

Animals↗

PubMed2002

Synapse formation is associated with memory storage in the cerebellum.

The idea that memory is encoded by means of synaptic growth is not new. However, this idea has been difficult to demonstrate in the mammalian brain because of both the complexity of mammalian behavior and the neural circuitry by which it is supported. Here we examine how eyeblink classical conditioning affects synapse number within the cerebellum; the brain region essential for long-term retention of the conditioned response. Results showed eyeblink-conditioned rats to have significantly more synapses per neuron within the cerebellar interpositus nucleus than both explicitly unpaired and untrained controls. Further analysis showed that the increase was caused by the addition of excitatory rather than inhibitory synapses. Thus, development of the conditioned eyeblink response is associated with a strengthening of inputs from precerebellar nuclei rather than from cerebellar cortex. These results demonstrate that the modifications of specific neural pathways by means of synaptogenesis contributes to formation of a specific memory within the mammalian brain.

Analysis of Variance↗

PubMed1989

Peripheral nerve damage facilitates functional innervation of brain grafts in adult sensory cortex.

The neural pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting "conditions" or "primes" the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis.

Animals↗

PubMed1990

N-acetylaspartylglutamate: a transmitter candidate for the retinohypothalamic tract.

The retinohypothalamic tract is the neural pathway mediating the photic entrainment of circadian rhythms in mammals. Important targets for these retinal fibers are the suprachiasmatic nuclei (SCN) of the hypothalamus, which are thought to be primary sites for the biological clock. The neurotransmitters that operate in this projection system have not yet been determined. Immunohistochemistry and radioimmunoassay performed with affinity-purified antibodies to N-acetylaspartylglutamate (NAAG) demonstrate that this neuron-specific dipeptide, which may act as an excitatory neurotransmitter, is localized extensively in the retinohypothalamic tract and its target zones, including the SCN. Optic nerve transections resulted in significant reductions in NAAG immunoreactivity in the optic chiasm and SCN. Analysis of NAAG concentrations in micropunches of SCN, by means of radioimmunoassay, showed approximately 50% reductions in NAAG levels. These results suggest that this peptide may act as one of the neurotransmitters involved in retinohypothalamic communication and circadian rhythm entrainment.

Animals↗

PubMed1992

Crossmodal changes in the somatosensory vibrissa/barrel system of visually deprived animals.

Cats deprived of vision from birth adapt remarkably well to their situation and show little behavioral impairment. They seem to compensate for their lack of vision by relying more on their auditory and tactile senses. We report here that the facial vibrissae, which are most important for tactile orientation in many animals, show supernormal growth in both cats and mice that have been deprived of vision from birth. Furthermore, the whisker representation in the somatosensory cortical barrel field shows a concomitant enlargement in binocularly enucleated mice: individual barrels are expanded in size by up to one-third. The increased use of the vibrissae in visually deprived animals may stimulate both their own growth and, via activation of the respective neural pathways, the expansion of their central representation.

Animals↗

PubMed1993

Electrophysiological tests of neural models: evidence for nonlinear binocular interactions in humans.

Evoked cortical potentials were used to test neural models of binocular interactions in humans. The critical feature that distinguished between basic models was whether the two monocular signals combined linearly or nonlinearly. Stimuli were presented separately and simultaneously to two eyes with the relative temporal phase parametrically varied. Fourier analysis was applied to the recorded electroencephalogram to measure the frequency response of the visual cortex to this stimulation. Comparisons of the models' predictions with the experimental results indicate that the greatest contribution to the cortical response originates in a neural pathway that contains nonlinear binocular combination, and a smaller contribution originates in a pathway with linear binocular combination. Current models, based on psychophysical studies of humans and on single-cell neurophysiological investigations of cats, are inadequate to explain these results. A model of binocular interaction is proposed that does account for the present findings and is also supported by neurophysiological studies on monkeys. This model, which contains both nonlinear and linear binocular interactions, has profound implications for perceptual processing.

Cerebral Cortex↗

PubMed1996

Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system.

Mice devoid of PrPC (Prnp%) are resistant to scrapie and do not allow propagation of the infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnp% brains but not the surrounding tissue consistently exhibits scrapie-specific pathology and allows prion replication after inoculation. Scrapie prions administered intraocularly into wild-type mice spread efficiently to the central nervous system within 16 weeks. To determine whether PrPC is required for scrapie spread, we inoculated prions intraocularly into Prnp% mice containing a PrP-overexpressing neurograft. Neither encephalopathy nor protease-resistant PrP (PrPSc) were detected in the grafts for up to 66 weeks. Because grafted PrP-expressing cells elicited an immune response that might have interfered with prion spread, we generated Prnp% mice immunotolerant to PrP and engrafted them with PrP-producing neuroectodermal tissue. Again, intraocular inoculation did not lead to disease in the PrP-producing graft. These results demonstrate that PrP is necessary for prion spread along neural pathways.

Animals↗

PubMed1996

Impaired hippocampal plasticity in mice lacking the Cbeta1 catalytic subunit of cAMP-dependent protein kinase.

Neural pathways within the hippocampus undergo use-dependent changes in synaptic efficacy, and these changes are mediated by a number of signaling mechanisms, including cAMP-dependent protein kinase (PKA). The PKA holoenzyme is composed of regulatory and catalytic (C) subunits, both of which exist as multiple isoforms. There are two C subunit genes in mice, Calpha and Cbeta, and the Cbeta gene gives rise to several splice variants that are specifically expressed in discrete regions of the brain. We have used homologous recombination in embryonic stem cells to introduce an inactivating mutation into the mouse Cbeta gene, specifically targeting the Cbeta1-subunit isoform. Homozygous mutants showed normal viability and no obvious pathological defects, despite a complete lack of Cbeta1. The mice were analyzed in electrophysiological paradigms to test the role of this isoform in long-term modulation of synaptic transmission in the Schaffer collateral-CA1 pathway of the hippocampus. A high-frequency stimulus produced potentiation in both wild-type and Cbeta1-/- mice, but the mutants were unable to maintain the potentiated response, resulting in a late phase of long-term potentiation that was only 30% of controls. Paired pulse facilitation was unaffected in the mutant mice. Low-frequency stimulation produced long-term depression and depotentiation in wild-type mice but failed to produce lasting synaptic depression in the Cbeta1 -/- mutants. These data provide direct genetic evidence that PKA, and more specifically the Cbeta1 isoform, is required for long-term depression and depotentiation, as well as the late phase of long-term potentiation in the Schaffer collateral-CA1 pathway.

Animals↗

PubMed1999

The mechanism of isoluminant chromatic motion perception.

An isoluminant chromatic display is a color display in which the component colors have been so carefully equated in luminance that they stimulate only color-sensitive perceptual mechanisms and not luminance-sensitive mechanisms. The nature of the mechanism by which isoluminant chromatic motion is perceived is an important issue because color and motion processing historically have been associated with different neural pathways. Here we show that isoluminant chromatic motion (i) fails a pedestal test, (ii) has a temporal tuning function that declines to half-amplitude at 3-6 Hz, and (iii) is perceived equally well when the entire motion sequence is presented monocularly (entire motion sequence to one eye) versus interocularly (the frames of motion sequence alternate between eyes so that neither eye individually could perceive motion). These three characteristics indicate that chromatic motion is detected by the third-order motion system. Based on this theory, it was possible to take a moving isoluminant red-green grating and, by simply increasing the chromatic contrast of the green component, to generate the full gamut of motion percepts, from compelling smooth motion to motion standstill. The perception of motion standstill when the third-order mechanism is nullified indicates that there is no other motion computation available for purely chromatic motion. It follows that isoluminant chromatic motion is not computed by specialized chromatic motion mechanisms within a color pathway but by the third-order motion system at a brain level where binocular inputs of form, color, depth, and texture are simultaneously available and where selective attention can exert a major influence.

Calibration↗

PubMed1999

Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation.

Previously, we reported that bilateral excitotoxic lesions of the basolateral nucleus of the amygdala (BLA) block the enhancing effects of posttraining systemic or intrahippocampal glucocorticoid administration on memory for inhibitory avoidance training. The present study further examined the basis of this permissive influence of the BLA on hippocampal memory functioning. Immediate posttraining unilateral infusions of the specific glucocorticoid receptor agonist RU 28362 (11beta,17beta-dihydroxy-6, 21-dimethyl-17alpha-pregna-4,6-trien-20-yn-3-one; 3.0, 10.0, or 30.0 ng in 0.5 microliter) administered into the dorsal hippocampus of male Sprague-Dawley rats induced dose-dependent enhancement of 48-h inhibitory avoidance retention. Infusions of the beta-adrenoceptor antagonist atenolol (0.5 microgram in 0.2 microliter) into the ipsilateral, but not the contralateral, BLA 10 min prior to training blocked the hippocampal glucocorticoid effects on memory consolidation. Infusions of the muscarinic cholinergic antagonist atropine (0.5 microgram in 0.2 microliter) into either the ipsilateral or contralateral BLA before training did not block the hippocampal glucocorticoid effects. These findings provide further evidence that beta-adrenergic activity in the BLA is essential in enabling glucocorticoid-induced modulation of memory consolidation and are consistent with the hypothesis that the BLA regulates the strength of memory consolidation in other brain structures. The ipsilateral nature of the BLA-hippocampus interaction indicates that BLA influences on hippocampal memory processes are mediated through neural pathways rather than by influences by means of the activation of peripheral stress responses.

Amygdala↗

PubMed1995

Control of vascular cell adhesion molecule-1 gene promoter activity during neural differentiation.

Here we demonstrate that vascular cell adhesion molecule-1 (VCAM-1) is expressed in the developing central nervous system on neuroepithelial cells, which are the precursors of neurons and glia. As these cells differentiate, VCAM-1 is restricted to a subset of the glial population. An understanding of mechanisms responsible for this restricted pattern could provide insights into how lineage-specific gene expression is maintained during neural differentiation. As a model of neural differentiation, we turned to the P19 embryonic carcinoma cell line, which in response to retinoic acid will differentiate along a neural pathway. We show that VCAM-1 expression on the differentiating P19 cells resembles that in the central nervous system. Transfection of VCAM-1 gene promoter constructs into P19 cells revealed that the VCAM-1 gene is controlled sequentially by negative and positive elements during differentiation. We present evidence that early during differentiation, POU proteins block VCAM-1 gene activity; however, later in differentiation coincident with the appearance of VCAM-1 the pattern of POU proteins changes and the VCAM-1 gene promoter is activated. This activation is mediated through the NF kappa B/rel complex p50/p65, which forms during P19 cell differentiation.

Animals↗

PubMed2000

Quantitative expression analysis of genes regulated by both obesity and leptin reveals a regulatory loop between leptin and pituitary-derived ACTH.

Absence of the hormone leptin leads to dramatic increases in appetite, food intake, and adiposity. The primary site of action, at least with respect to appetite, is the hypothalamus. Leptin also has significant effects on the function(s) of peripheral organs involved in maintaining body composition. Some of these effects are mediated through direct interaction of leptin with its receptor on the target tissue, and some effects are indirectly mediated through secondary hormonal and neural pathways. Few of the genes that are responsible for regulating body composition and the peripheral effects of leptin are known. We have used a new gene profiling technology to characterize gene expression changes that occur in the pituitary, hypothalamus, fat, muscle, and liver in response to both obesity and treatment with exogenous leptin. These differences were then overlaid to allow the identification of genes that are regulated by obesity and at least partially normalized by leptin treatment. By using this process we have identified five genes (POMC, PC2, prolactin, HSGP25L2G, and one novel) that are both abnormally expressed in the pituitaries of obese mice and are sensitive to the effects of leptin. We also show that adrenocorticotropic hormone appears to be involved in a regulatory loop involving leptin.

Adipose Tissue↗

PubMed2005

A novel pineal-specific product of the oligopeptide transporter PepT1 gene: circadian expression mediated by cAMP activation of an intronic promoter.

The oligopeptide transporter 1, PepT1, is a member of the Slc15 family of 12 membrane-spanning domain transporters; PepT1 has proton/peptide cotransport activity and is selectively expressed in intestinal epithelial cells, where it is responsible for the nutritional absorption of di- and tri-peptides. Here, a novel PepT1 gene product has been identified in the rat pineal gland, termed pgPepT1. It encodes a 150-amino acid protein encompassing the C-terminal 3 membrane-spanning domains of intestinal PepT1 protein, with 3 additional N-terminal residues. Expression of pgPepT1 appears to be restricted to the pineal gland and follows a marked circadian pattern with >100-fold higher levels of mRNA occurring at night; this is accompanied by an accumulation of membrane-associated pgPepT1 protein ( approximately 16 kDa). The daily rhythm in pgPepT1 mRNA is regulated by the well described neural pathway that controls pineal melatonin production. This includes the retina, the circadian clock in the suprachiasmatic nucleus, central structures, and projections from the superior cervical ganglia; activation of this pathway results in the release of norepinephrine. Here it was found that pgPepT1 expression is mediated by a norepinephrine-->cyclic AMP mechanism that activates an alternative promoter located in intron 20 of the gene. pgPepT1 protein was found to have transporter-modulator activity; it could contribute to circadian changes in pineal function through this mechanism.

Amino Acid Sequence↗

PubMed1999

Cardiorespiratory responses to interleukin-1beta in adult rats: role of nitric oxide, eicosanoids and glucocorticoids.

Interleukin-1beta (IL-1beta) receptors are abundantly expressed in brain stem regions involved in respiratory control. We hypothesized that systemic administration of IL-1beta would increase ventilation (V(E )), and that nitric oxide, eicosanoids, and glucocorticoid receptors would modulate IL-1beta-induced cardioventilatory responses. Intravenous injections of three doses (37.5 ng kg(-1), 75 ng kg(-1 ) and 150 ng kg(-1)) of IL-1b induced monophasic increases in (V(E)), heart rate (HR), and blood pressure (BP) which had a distinctly different onset and duration of action compared to IL-1beta-induced body temperature elevations. Pre-treatment with the nitric oxide inhibitor L-NAME was associated with decreased peak V(E) responses, without affecting the latency and duration of IL-1beta. L-NAME also enhanced HR responses while pressor responses were attenuated. Eicosanoid inhibition with indomethacin resulted in markedly attenuated V responses. However, cardiovascular responses to IL-1beta were not modified by indomethacin. In contrast, pre-treatment with dexamethasone, was not associated with any changes in the IL-1beta-induced V(E), HR, or BP responses. We conclude that IL-1beta increases of V(E) are dose-dependent and are not time-locked with the pyrexic response suggesting the possibility that distinct neural pathways may underlie these responses. In addition, nitric oxide and eicosanoid-dependent mechanisms modulate IL-1beta ventilatory effects.

Animals↗

PubMed2001

The regulation of body weight: lessons from the seasonal animal.

The hypothalamus is a major regulatory centre involved in the control of many important physiological axes. One of these axes is the regulation of ingestive behaviour. Recent work using a combination of genetic-mutant mouse models together with targeted gene deletions has contributed much to our understanding of how neural pathways of the hypothalamus are involved in the regulation of energy balance in animals. These pathways are also relevant to human energy homeostasis. as mutations in key genes are correlated with obesity. Many of the genes identified mediate the effects of leptin, and are therefore primarily involved in sensing and responding to peripheral signals. In seasonal animals, such as the Siberian hamster (Phodopus sungorus), there is evidence for a higher level of regulation. The systems involved regulate body weight around an apparent 'set-point' through the action of photoperiod via the neurohormone, melatonin. The ability to manipulate energy balance through photoperiod (and melatonin) in the seasonal-animal model offers novel opportunities to identify further fundamental aspects of the control mechanisms involved in the central control of energy homeostasis and body weight.

Animals↗