[Abstract Title]. - Society for Neuroscience

231. Dendrite Growth and Branching: Signaling
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 231.15/B28
Topic: A.04.i. Dendritic growth and branching
Support: NIH Grant NS29837
Title: The change of dendrite morphology of spinal cord neurons with GluR1 knockdown
Authors: *L. ZHANG 1 , M. WERNER 2 , J. MOJSILOVIC-PETROVIC 1 , G. XIONG 1 , M.
HOLLMANN 2 , R. KALB 1 ;
1 Dept Neurol, Children Hosp. Philadelphia, Univ. Pennsylvania, Philadelphia, PA; 2 Dept. of
Biochem. I - Receptor Biochem., Ruhr Univ. Bochum, Bochum, Germany
Abstract: The glutamate receptor subunit GluR1 is likely to play an essential role in motor
neuron development. GluR1 is expressed abundantly by neonatal motor neurons (as well as
surrounding interneurons) coincident with active dendrite growth. Although GluR1 expression is
down regulated in mature motor neurons, reintroduction of GluR1 causes the remodeling of the
architecture of dendrites of mature motor neurons. We used RNAi to investigate whether the
actions of GluR1 are solely cell autonomous. We generated RNAi to GluR1 that specifically
knockdown GluR1 in neurons. By linking this small RNA to the vector peptide Penetratin 1, we
were able to knock down GluR1 in virtually all neurons in vitro and this led to a marked
reduction in dendrite size and complexity. Next we engineered this small RNA into pSUPER so
that only individual transfected neurons will have GluR1 knockdown. In this paradigm,
knockdown of GluR1 also reduced dendrite size and complexity. These observations suggest that
GluR1 promotes dendrite growth in a cell autonomous manner. Finally we generated a version of
GluR1 that resists the knockdown of our RNAi. In cultures transfected with this construct and
treated with penetratin-linked RNAi, the expression of GluR1 was reduced in all neurons except
the one we analyzed that express wild type levels of GluR1. Surprisingly, in this paradigm,
despite expressing GluR1, neurons had reduced dendrite size and complexity. Thus GluR1 does
not operate in a strictly cell autonomous manner to promote dendrite elaboration. These results
were also seen in vivo when we analyzed the dendritic tree of motor neurons from GluR1 (aka
GluR-A) knock out animals as well as animals with a conditional knockout of GluR1 specifically
in motor neurons These experiments provide insight into how GluR1 plays an important role in
regulating the normal development of the motor system.
Disclosures: L. Zhang, None; M. Werner, None; J. Mojsilovic-Petrovic, None; G. Xiong,
None; R. Kalb, None; M. Hollmann, None.
Poster