Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins.

Cerebellar LTD requires activation of PKC and is expressed, at least in part, as postsynaptic AMPA receptor internalization. Recently, it was shown that AMPA receptor internalization requires clathrin-mediated endocytosis and depends upon the carboxy-terminal region of GluR2/3. Phosphorylation of Ser-880 in this region by PKC differentially regulates the binding of the PDZ domain-containing proteins GRIP/ABP and PICK1.

Bone formation into surface phosphonylated polymeric implants.

Through the use of two animal models, the present study demonstrates the ability of phosphonylated surfaces to bind bone. In one model, surface-treated polypropylene (PP) and polyethylene (PE) were implanted in the medial cortex of the goat tibia. In the second model, surface-treated poly(ether-ether ketone) (PEEK) and carbon fiber-reinforced PEEK (CFR-PEEK) were implanted through both cortices of the goat mandible.

Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes.

The aim of this study was to investigate the direct effects of growth hormone (GH) on production and secretion of apolipoprotein B (apoB)-containing lipoproteins from hepatocytes. Bovine GH (5-500 ng/ml) was given for 1 or 3 days to rat hepatocytes cultured on laminin-rich matrigel in serum-free medium. The effects of GH were compared with those of 3 nM insulin and 500 microM oleic acid.

Spatial pattern of cerebral glucose metabolism (PET) correlates with localization of intracerebral EEG-generators in Alzheimer's disease.

Background: Since the measurement of human cerebral glucose metabolism (GluM) by positron emission tomography (PET) and that of human cerebral electrical activity by EEG reflect synaptic activity, both methods should be related in their cerebral spatial distribution. Healthy subjects do indeed demonstrate similar metabolic and neuroelectric spatial patterns.

Objective: The aim of the study was to show that this similarity of GluM and EEG spatial patterns holds true in a population with a high variability of glucose metabolism.

Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice.

The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons.

Time-dependent changes in neurokinin(3) receptors and tachykinins during adjuvant-induced peripheral inflammation in the rat.

Although considerable evidence exists that spinal neurokinin(1) receptors are involved in central sensitization of nociception, recent evidence from knockout studies indicates that other neurokinin receptors in the spinal cord may mediate a portion of the hyperalgesia caused by substance P and neurokinin A. The present study determined whether the second most abundant class of neurokinin receptors, neurokinin(3) receptors, are regulated during persistent peripheral inflammation. Inflammation in the hind paw of the rat was induced by intraplantar injection of complete Freund's adjuvant.

Matching two imagined clocks: the functional anatomy of spatial analysis in the absence of visual stimulation.

Do spatial operations on mental images and those on visually presented material share the same neural substrate? We used the high spatial resolution of functional magnetic resonance imaging to determine whether areas in the parietal lobe that have been implicated in the spatial transformation of visual percepts are also activated during the generation and spatial analysis of imagined objects. Using a behaviourally controlled mental imagery paradigm, which did not involve any visual stimulation, we found robust activation in posterior parietal cortex in both hemispheres. We could thus identify the subset of spatial analysis-related activity that is involved in spatial operations on mental images in the absence of external visual input.

Long-term depression of the cerebellar climbing fiber--Purkinje neuron synapse.

In classic Marr-Albus-Ito models of cerebellar function, coactivation of the climbing fiber (CF) synapse, which provides massive, invariant excitation of Purkinje neurons (coding the unconditioned stimulus), together with a graded parallel fiber synaptic array (coding the conditioned stimulus) leads to long-term depression (LTD) of parallel fiber-Purkinje neuron synapses, underlying production of a conditioned response. Here, we show that the supposedly invariant CF synapse can also express LTD. Brief 5 Hz stimulation of the CF resulted in a sustained depression of CF EPSCs that did not spread to neighboring parallel fiber synapses.

D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor.

Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist. Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine. We now show that selective degradation of d-serine with D-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux.

Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis.

Cerebellar long-term depression (LTD) is a cellular model system of information storage that may underlie certain forms of motor learning. While cerebellar LTD is expressed as a selective modification of postsynaptic AMPA receptors, this might involve changes in receptor number/distribution, unitary conductance, kinetics, or glutamate affinity. The observation that GluR2-containing synaptic AMPA receptors could be internalized by regulated clathrin-mediated endocytosis suggested that this process could underlie LTD expression.

Neurokinin(3) receptors couple to the activation of neuronal nitric-oxide synthase in stably transfected Chinese hamster ovary cells.

Several physiological effects induced by activation of neurokinin(3) (NK(3)) receptors are mediated by the production of nitric oxide (NO). We investigated the intracellular coupling of NK(3) receptors to NO synthase (NOS) using a Chinese hamster ovary cell line that was stably transfected with both the NK(3) receptor and type I (neuronal) NOS. NOS activity in the transfected cell line was assayed directly, by measuring the formation of L-citrulline, another product of NOS, as well as indirectly, by measuring the production of cGMP in cultured rat fetal lung fibroblasts (RFL-6 cells).

Cannabinoid receptor modulation of synapses received by cerebellar Purkinje cells.

The high density of cannabinoid receptors in the cerebellum and the degradation of motor coordination produced by cannabinoid intoxication suggest that synaptic transmission in the cerebellum may be strongly regulated by cannabinoid receptors. Therefore the effects of exogenous cannabinoids on synapses received by Purkinje cells were investigated in rat cerebellar slices. Parallel fiber-evoked (PF) excitatory postsynaptic currents (EPSCs) were strongly inhibited by bath application of the cannabinoid receptor agonist WIN 55212-2 (5 microM, 12% of baseline EPSC amplitude).

The myth of upright vision. A psychophysical and functional imaging study of adaptation to inverting spectacles.

The adaptation to inverting prisms and mirror spectacles was studied in four subjects over periods of six to ten days. Subjects showed rapid adaptation of visuomotor functions, but did not report return of upright vision. The persistence of the transformed visual image was confirmed by the subjects' perception of shape from shading.

[Differential orthostatic dysregulation disorders diagnosis].

Orthostatic circulatory disorders are frequently the cause of orthostatic intolerance, syncope or dangerous falls. A sufficient therapy should be based on a differential diagnosis by means of an active standing test or a tilt-table test. Three typical pathological reactions of blood pressure and heart rate can be differentiated.

The functional neuroanatomy of target detection: an fMRI study of visual and auditory oddball tasks.

The neuronal response patterns that are required for an adequate behavioural reaction to subjectively relevant changes in the environment are commonly studied by means of oddball paradigms, in which occasional 'target' stimuli have to be detected in a train of frequent 'non-target' stimuli. The detection of such task-relevant stimuli is accompanied by a parietocentral positive component of the event-related potential, the P300. We performed EEG recordings of visual and auditory event-related potentials and functional magnetic resonance imaging (fMRI) when healthy subjects performed an oddball task.

Activation of presynaptic cAMP-dependent protein kinase is required for induction of cerebellar long-term potentiation.

Cerebellar long-term potentiation (LTP) is a persistent increase in the strength of the granule cell-Purkinje neuron synapse that occurs after brief stimulation of granule cell axons at 2-8 Hz. Previous work has indicated that cerebellar LTP induction requires presynaptic Ca influx, stimulation of Ca-sensitive adenylyl cyclase, and activation of PKA. The evidence implicating PKA has come from bath application of drugs during LTP induction, an approach that does not distinguish between PKA activation in the presynaptic or postsynaptic cell.

Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum.

Current-clamp recordings were made from the deep cerebellar nuclei (DCN) of 12- to 15-day-old rats to understand the factors that mediate intrinsic spontaneous firing patterns. All of the cells recorded were spontaneously active with spiking patterns ranging continuously from regular spiking to spontaneous bursting with the former predominating. A robust rebound depolarization (RD) leading to a Na(+) spike burst was elicited after the offset of hyperpolarizing current injection.

Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III.

Facial nerve function was studied in 19 patients with hereditary motor and sensory neuropathy type I (HMSN I) and 2 patients with hereditary motor and sensory neuropathy type III (HMSN III, Déjérine-Sottas), and compared to that in 24 patients with Guillain-Barré syndrome (GBS). The facial nerve was stimulated electrically at the stylomastoid fossa, and magnetically in its proximal intracanalicular segment. Additionally, the face-associated motor cortex was stimulated magnetically.

A late phase of cerebellar long-term depression requires activation of CaMKIV and CREB.

Recently, it has been shown that cerebellar LTD has a late phase that may be blocked by protein synthesis inhibitors. To understand the mechanisms underlying the late phase, we interfered with the activation of transcription factors that might couple synaptic activation to protein synthesis. Particle-mediated transfection of cultured Purkinje neurons with an expression vector encoding a dominant inhibitory form of CREB resulted in a nearly complete blockade of the late phase.

Cerebrovascular mechanisms in neurocardiogenic syncope with and without postural tachycardia syndrome.

Background And Purpose: Recent transcranial Doppler studies in patients with neurocardiogenic syncopes (NCS) have demonstrated that the cerebrovascular response to sudden systemic hypotension is vasoconstriction instead of compensatory vasodilation (autoregulation). We tried to characterize the conditions leading to this unexpected response in NCS patients further by continuously monitoring autoregulation and autonomic parameters during a standardized tilt-table test (TTT).

Methods: Sixteen patients below the age of 50 years with a history of at least three syncopes of undetermined cause and tilt-table verified NCS and 20 normal controls were studied.

Exploring brain function with magnetic resonance imaging.

Since its invention in the early 1990s, functional magnetic resonance imaging (fMRI) has rapidly assumed a leading role among the techniques used to localize brain activity. The spatial and temporal resolution provided by state-of-the-art MR technology and its non-invasive character, which allows multiple studies of the same subject, are some of the main advantages of fMRI over the other functional neuroimaging modalities that are based on changes in blood flow and cortical metabolism. This paper describes the basic principles and methodology of fMRI and some aspects of its application to functional activation studies.

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects.