Glutamate receptor mediated regulation of dendrite morphogenesis in developing spinal motor neurons
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Description
As development proceeds in spinal motor neurons, there is a period of increased dendrite proliferation followed by a period during which arbor is lost. While the exact molecular mechanisms underlying these changes are unknown, activity-dependent processes have been implicated. Since both the AMPA and NMDA subtypes of glutamate receptors are developmentally regulated in spinal motor neurons, we investigated the role played by changes in AMPA and NMDA receptor subunit expression levels in the establishment of mature motor neuron dendrite architecture. We found that over-expression of the GluR1 AMPA receptor subunit caused a significant increase in the total amount and complexity of dendrite arbor with an increase in filopodial numbers. GluR1 over-expression also caused an increase in the number of GFP-labeled PSD95 puncta, suggesting an increase in the number of excitatory synapses in transfected cells. On the contrary, over-expression of the GluR2 AMPA receptor subunit was associated with a modest increase in total dendrite arbor, decreased filopodial numbers and no changes in dendrite complexity or number of PSD95 puncta. These results suggest that GluR1 may facilitate motor neuron dendrite outgrowth and branching by promoting excitatory synaptogenesis and the outgrowth of filopodia while GluR2, present at high levels in adult motor neurons, may act to stabilize existing motor neuron dendrite branching by inhibiting filopodial extension. Analysis of local protein translation in motor neuron dendrites by CPEB showed that while the GluR1 mediated effects on dendrite branching may be independent of CPEB, local synthesis of GluR2 or an associated protein may be involved Over-expression of the NR3B NMDA receptor subunit, which acts as a dominant-negative subunit and is up-regulated in adult motor neurons, resulted in increased amount and complexity of dendrite arbor with higher numbers of filopodia. Administration of AP5, an NMDA receptor antagonist, caused a re-organization of dendrite arbor without any changes in numbers of filopodia or amount and complexity of dendrite arbor. Thus, our results indicate that NR3B plays a role in the activity-dependent regulation of dendrite branching, but in a manner that is inconsistent with loss of NMDA receptor activity