TY - JOUR
T1 - The role of nitric oxide and NMDA receptors in the development of motor neuron dendrites
AU - Inglis, Fiona M.
AU - Furia, Fran
AU - Zuckerman, Katharine E.
AU - Strittmatter, Stephen M.
AU - Kalb, Robert G.
PY - 1998/12/15
Y1 - 1998/12/15
N2 - Nitric oxide (NO) has been implicated in the establishment of precise synaptic connectivity throughout the neuroaxis in several species. To determine the contribution of NO to NMDA receptor-dependent dendritic growth in motor neurons, we administered the NMDA antagonist MK-801 to wild-type mice and neuronal nitric oxide synthase (nNOS) knock-out mice between postnatal days 7 and 14. Compared to saline-treated wild-type animals the number of dendritic bifurcations was significantly reduced in nNOS knock-out animals and MK-801-treated wildtype animals. There was no significant difference in dendritic bifurcation between MK-801-treated wild-type, MK- 801-treated nNOS knock-out, and saline-treated nNOS knock-out animals, suggesting that nNOS knock-out and NMDA receptor block had similar effects. The path of the longest dendrite and the number of primary dendrites was the same in all treatment groups, indicating an effect specific to bifurcation. Sholl analysis revealed that differences in bifurcation numbers occurred between 160 and 320 μm from the cell body, the distance at which second, third, and fourth order dendrites are most prevalent. Dendrite order analyses confirmed a significant reduction in numbers, but not lengths, of third and fourth order dendrites in nNOS knock-out and drug-treatment groups. Finally, immunohistochemical examination of the developing spinal cord indicated that NMDA receptors and nNOS are colocalized within interneurons surrounding the motor neuron pool. These results support the view that at least part of NMDA receptor-dependent arborization of motor neuron dendrites is mediated by the local production of NO within the developing spinal cord.
AB - Nitric oxide (NO) has been implicated in the establishment of precise synaptic connectivity throughout the neuroaxis in several species. To determine the contribution of NO to NMDA receptor-dependent dendritic growth in motor neurons, we administered the NMDA antagonist MK-801 to wild-type mice and neuronal nitric oxide synthase (nNOS) knock-out mice between postnatal days 7 and 14. Compared to saline-treated wild-type animals the number of dendritic bifurcations was significantly reduced in nNOS knock-out animals and MK-801-treated wildtype animals. There was no significant difference in dendritic bifurcation between MK-801-treated wild-type, MK- 801-treated nNOS knock-out, and saline-treated nNOS knock-out animals, suggesting that nNOS knock-out and NMDA receptor block had similar effects. The path of the longest dendrite and the number of primary dendrites was the same in all treatment groups, indicating an effect specific to bifurcation. Sholl analysis revealed that differences in bifurcation numbers occurred between 160 and 320 μm from the cell body, the distance at which second, third, and fourth order dendrites are most prevalent. Dendrite order analyses confirmed a significant reduction in numbers, but not lengths, of third and fourth order dendrites in nNOS knock-out and drug-treatment groups. Finally, immunohistochemical examination of the developing spinal cord indicated that NMDA receptors and nNOS are colocalized within interneurons surrounding the motor neuron pool. These results support the view that at least part of NMDA receptor-dependent arborization of motor neuron dendrites is mediated by the local production of NO within the developing spinal cord.
KW - Dendrite
KW - Development
KW - Motor neuron
KW - NMDA receptor
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Spinal cord
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=0032535277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032535277&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.18-24-10493.1998
DO - 10.1523/jneurosci.18-24-10493.1998
M3 - Article
C2 - 9852587
AN - SCOPUS:0032535277
SN - 0270-6474
VL - 18
SP - 10493
EP - 10501
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 24
ER -