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The Journal of Neuroscience, April 15, 1999, 19(8):3007-3022
Cholinergic and GABAergic Inputs Drive Patterned Spontaneous
Motoneuron Activity before Target Contact
Louise D.
Milner and
Lynn T.
Landmesser
Department of Neurosciences, Case Western Reserve University,
School of Medicine, Cleveland, Ohio 44106
Patterned spontaneous electrical activity has been demonstrated in
a number of developing neural circuits and has been proposed to play a
role in refining connectivity once axons reach their targets. Using an
isolated spinal cord preparation, we have found that chick lumbosacral
motor axons exhibit highly regular bursts of activity from embryonic
day 4 (E4) (stage 24-25), shortly after they exit the
spinal cord and while still en route toward their target muscles.
Similar bursts could be evoked by stimulating descending pathways at
cervical or thoracic levels. Unlike older embryonic cord circuits, the
major excitatory transmitter driving activity was not glutamate but
acetylcholine, acting primarily though nicotinic non- 7
receptors. The circuit driving bursting was surprisingly robust and
plastic, because bursting was only transiently blocked by cholinergic
antagonists, and following recovery, was now driven by GABAergic
inputs. Permanent blockade of spontaneous activity was only achieved by
a combination of cholinergic antagonists and bicuculline, a
GABAA antagonist. The early occurrence of patterned motor
activity suggests that it could be playing a role in either peripheral
pathfinding or spinal cord circuit formation and maturation. Finally,
the characteristic differences in burst parameters already evident
between different motoneuron pools at E4 would require that the
combination of transcription factors responsible for specifying pool
identity to have acted even earlier.
Key words:
motoneurons; spontaneous neural activity; rhythmicity; nicotinic receptors; GABA; cholinergic inputs; spinal cord
interneurons; embryonic networks
Copyright © 1999 Society for Neuroscience 0270-6474/99/1983007-16$05.00/0
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