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S Hockfield

Publications and source records attributed to S Hockfield.

76 records · Page 5Linked to original sources

Activity-dependent development of spinal cord motor neurons.

Patterned neuronal activity in early postnatal life can regulate the acquisition of the mature morphological and electrophysiological properties of neurons. Many properties of motor neurons are developmentally regulated and may be influenced by epigenetic factors. The pattern of activation of motor neurons can regulate axon terminal morphology and synaptic efficacy at the neuromuscular junction. Motor neuron morphology and synaptic connections can also be modified by exposure to specific hormones in the early postnatal period. The acquisition of mature physiological and anatomical properties is paralleled by the acquisition of specific molecular properties. Recent experiments using molecular markers for motor neuron differentiation indicate that motor neurons undergo activity-dependent development during a circumscribed period in early postnatal life. Normal motor neuron differentiation requires a normal pattern of neuronal activity in early postnatal life. Differentiation also requires activation of the NMDA receptor over the same time period. The activity-dependent development of morphological, electrophysiological and molecular properties of motor neurons is similar to activity-dependent development in the vertebrate visual system. The neuromuscular system may provide an accessible system for characterizing the molecules subserving the translation of patterned neuronal activity into mature neuronal phenotype.

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Monoclonal antibody that identifies subsets of neurones in the central visual system of monkey and cat.

Striking correlations between structure and function are found in the visual cortex of Old World primates. These include the co-localization of glutamic acid decarboxylase (GAD, the biosynthetic enzyme of the inhibitory neurotransmitter, gamma-aminobutyric acid) with the mitochondrial enzyme, cytochrome oxidase (CO) in functionally distinct subcompartments of ocular dominance columns. We report here immunocytochemical studies with a monoclonal antibody (CAT 301) showing that the antibody recognizes an uncharacterized antigen on surfaces of some neurones in certain layers of the monkey striate cortex (area 17), and in certain parts of the cat and monkey dorsal lateral geniculate nuclei (LGN). Patches of immunocytochemically stained neurones and neuropil, apparent in layers III, IVB and VI of the striate cortex of normal monkeys, become even more clearly delineated in animals from which one eye has been removed. The antibody-stained patches in the three layers line up radially with one another in lines passing through the centres of ocular dominance columns (demonstrable by CO staining in layers IVA and IVC). In layers III and VI the patches coexist with CO-positive patches and, in the horizontal dimension, both antibody and CO-positive patches are aligned to form rows. Stained neurones in the monkey LGN are primarily in the magnocellular layers and in the cat LGN are confined to laminae A and A1, the inter-laminar plexuses, the perigeniculate nucleus and the medial inter-laminar nucleus. The antigen we have localized is associated with particular cell populations, some of which may correspond to a specific, physiological class.

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Identification of proteins downregulated during the postnatal development of the cat visual cortex.

To identify proteins that play a role in the development of the mammalian visual cortex, we have used an immunosuppression and rapid immunization strategy to generate monoclonal antibodies to antigens that are present in area 17 of the cat during the peak of cortical plasticity but are downregulated near the end of the plastic period. We report here the immunohistochemical and immunobiochemical characterization of six monoclonal antibodies that identify antigens preferentially expressed in the cat visual cortex at 5 weeks of age. Monoclonal antibodies Cat-305 and Cat-306 detect three immunoreactive elements that are not present at birth but are present at 5 weeks. The majority of immunoreactivity is associated with a population of cells in the white matter that are absent at 15 weeks of age. At both 5 and 15 weeks, a very small number of neurons show intense immunoreactivity throughout all processes, resembling that achieved with a Golgi stain. In addition, a diffuse band of immunoreactivity in layer IV is largely restricted to cortical areas 17 and 18. Cat-307 recognizes a 150 kDa soluble protein present in small cytoplasmic inclusions. These cytoplasmic "dot" are present in all layers, but are most prominent in layer V. Cat-307 immunoreactivity is present at birth and is completely downregulated by 15 weeks. Cat-104 and Cat-105 recognize a 200 kDa insoluble protein present at birth and at 5 weeks, but markedly downregulated by 15 weeks. At birth, the white matter, subplate, and layer I are most densely labeled, while at 5 weeks labeling is densest in layers II, III, and V. Cat-402 recognizes a number of high-molecular-weight antigens that are differentially expressed at 5 and 15 weeks of age. Stained non-neuronal cells that resemble protoplasmic astrocytes are present in all layers at both 5 and 15 weeks. At 5 weeks, but not at birth or 15 weeks, darkly immunoreactive radial processes are observed that run through the full depth of the cortex. We show here that immunoreactivity for several different monoclonal antibodies is detected selectively during the period of maximal developmental plasticity. The results demonstrate that the cat visual cortex at 5 weeks of age is molecularly distinct from the cortex at 15 weeks.

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