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Volume 17, Number 6, Issue of March 15, 1997 pp. 2006-2017
Copyright ©1997 Society for Neuroscience

Differential Subcellular Regulation of NMDAR1 Protein and mRNA in Dendrites of Dentate Gyrus Granule Cells after Perforant Path Transection

Received Oct. 28, 1996; revised Dec. 23, 1996; accepted Jan. 3, 1997.

Adam H. Gazzaley1, 2, Deanna L. Benson1, George W. Huntley1, and John H. Morrison1, 2, 3

1 Fishberg Research Center for Neurobiology, 2 Laboratories for Neurobiology of Aging, and 3 Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York 10029

Unilateral transection of the excitatory perforant path results in the acute deafferentation of a segregated zone on the distal dendrites of hippocampal dentate gyrus granule cells (i.e., outer molecular layer), followed by sprouting, reactive synaptogenesis, and a return of physiological and behavioral function. To investigate cellular mechanisms underlying NMDA receptor plasticity in response to such extensive synaptic reorganization, we quantitatively evaluated changes in intensity levels of NMDAR1 immunofluorescence and NMDAR1 mRNA hybridization within subcellular compartments of dentate gyrus granule cells 2, 5, and 9 d after perforant path lesions. There were no significant changes in either measure at 2 d postlesion. However, at 5 and 9 d postlesion, during the period of axonal sprouting and synaptogenesis, there was an increase in NMDAR1 immunolabeling that was restricted to the dendritic segments of the denervated outer molecular layer and the granule cell somata. In contrast, NMDAR1 mRNA levels at 5 and 9 d postlesion increased throughout the full extent of the molecular layer, including both denervated and nondenervated segments of granule cell dendrites. These findings reveal that NMDAR1 mRNA is one of a limited population of mRNAs that is transported into dendrites and further suggest that in response to terminal proliferation and sprouting, increased mRNA transport occurs throughout the full dendritic extent, whereas increased local protein synthesis is restricted to denervated regions of the dendrites whose afferent activity is perturbed. These results begin to elucidate the dynamic postsynaptic subcellular regulation of receptor subunits associated with synaptic plasticity after denervation.

Key words: excitatory amino acid receptors; immunocytochemistry; hippocampus; entorhinal cortex; plasticity; confocal microscopy




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