DIFFERENTIAL SUBCELLULAR REGULATION OF NMDAR1 PROTEIN AND MESSENGER-RNA IN DENDRITES OF DENTATE GYRUS GRANULE CELLS AFTER PERFORANT PATH TRANSECTION

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 phys iological and behavioral function. To investigate cellular mechanisms underlying NMDA receptor plasticity in response to such extensive syna ptic reorganization, we quantitatively evaluated changes in intensity levels of NMDAR1 immunofluorescence and NMDAR1 mRNA hybridization with in 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, du ring the period of axonal sprouting and synaptogenesis, there was an i ncrease 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 increa sed 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 mR NAs that is transported into dendrites and further suggest that in res ponse to terminal proliferation and sprouting, increased mRNA transpor t occurs throughout the full dendritic extent, whereas increased local protein synthesis is restricted to denervated regions of the dendrite s whose afferent activity is perturbed. These results begin to elucida te the dynamic postsynaptic subcellular regulation of receptor subunit s associated with synaptic plasticity after denervation.