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

Abstract

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.

A Phosphorylated Cytoplasmic Autoantigen, GW182, Associates with a Unique Population of Human mRNAs within Novel Cytoplasmic Speckles

“…It might also be that GW182 is involved in degradation of mRNA but GWBs do not colocalize with the SCF ubiquitin ligase-mediated pathway for protein degradation. Along these lines of discussion, the GWBs described in this study may be related to mRNA-associated particles described in other systems, particularly neuronal cells (Triedge et al, 1991;Miyashiro et al, 1994;Knowles et al, 1996;Martone et al, 1996;Gazzaley et al, 1997;Racca et al, 1997;Bassell et al, 1998;Steward et al, 1998). In oligodendrocytes, injected fluorescent-labeled myelin basic protein mRNA localized to granules that had a radius of 0.6 -0.8 m, contained elongation factors, rRNA and other mRNAs.…”

Transport of Fragile X Mental Retardation Protein via Granules in Neurites of PC12 Cells

“…A number of mRNAs have been reported to be selectively targeted to dendrites of neurons, and these include for instance mRNAs for MAP2, Arc, CaMKII␣, and glutamate receptors (7,16,22,29). There is evidence that for dendrites an active sorting mechanism is involved.…”

Protein synthesis in the dendrite

“…It would be interesting to see if synthesis of these plasticity-related proteins after LTP induction involves local translation mechanisms. Several other mRNAs that encode plasticityrelated proteins, such as NMDA receptor subunits, BDNF and TrkB, are detected in dendrites (Benson 1997;Gazzaley et al 1997;Tongiorgi et al 1997). It remains to be examined if synaptic stimulation can result in local translation from these dendritic mRNAs.…”