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Knowledge of the effect of dopamine on corticostriatal synaptic plasticity has advanced rapidly over the last 5 years. We consider this new knowledge in relation to three factors proposed earlier to describe the rules for synaptic plasticity in the corticostriatal pathway. These factors are a phasic increase in dopamine release, presynaptic activity and(More)
BACKGROUND Members of the family of matrix metalloproteinases (MMPs; also called collagenases or matrixins) are key enzymes in matrix degradation. They function at neutral pH and can digest synergistically all the matrix macromolecules. Biochemical and clonal studies indicate that there are three major groups: the specific collagenases cleave interstitial(More)
The spiny projection neurons of the neostriatum are a site at which dopamine inputs from the substantia nigra converge with excitatory inputs from the cerebral cortex. These two systems interact in certain learning and motor control mechanisms of the brain. We investigated these interactions using intracellular recording from spiny striatal neurons in(More)
Exposure of quiescent MRC-5 human fibroblasts to growth factors such as epidermal growth factor, basic fibroblast growth factor or embryonal carcinoma-derived growth factor resulted in the induction of mRNA transcripts encoding the metalloproteinases collagenase and stromelysin and the specific metalloproteinase inhibitor TIMP, whilst expression of collagen(More)
The production of collagenase and collagenase inhibitor (TIMP) by various intracranial tumors (25 meningiomas, eight gliomas, seven metastases, four pituitary adenomas, and five others) was studied in short-term organ culture. While meningiomas produced negligible amounts of collagenase, two metastatic carcinomas of bronchial and breast origin produced(More)
Maintenance of DNA integrity is crucial for all cell types, but neurons are particularly sensitive to mutations in DNA repair genes, which lead to both abnormal development and neurodegeneration. We describe a previously unknown autosomal recessive disease characterized by microcephaly, early-onset, intractable seizures and developmental delay (denoted(More)
Striatal cholinergic interneurons, also known as tonically active neurons (TANs), acquire a pause in firing during learning of stimulus-reward associations. This pause response to a sensory stimulus emerges after repeated pairing with a reward. The conditioned pause is dependent on dopamine from the substantia nigra, but its underlying cellular mechanism is(More)
Inhibitory projections from the striatum and globus pallidus converge onto GABAergic projection neurons of the substantia nigra pars reticulata (SNr). Based on existing structural and functional evidence, these pathways are likely to differentially regulate the firing of SNr neurons. We sought to investigate the functional differences in inhibitory(More)
Collagen fibres form the stable architecture of connective tissues and their breakdown is a key irreversible step in many pathological conditions. The destruction of collagen is usually initiated by proteinases, the best known of which is the metalloproteinase collagenase (EC 3.4.24). Collagenase and related metalloproteinases are regulated at the level of(More)
Collagenase production by rodent osteoblasts in response to calciotropic hormones has led to the hypothesis that bone cells play a major role in bone resorption by degrading the surface osteoid layer, thereby exposing the underlying mineralized matrix to osteoclastic action. Many studies suggest, however, that this model might not apply to bone resorption(More)