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The Journal of Neuroscience, January 15, 2003, 23(2):587-600
Characterization of the Circuits That Generate Spontaneous
Episodes of Activity in the Early Embryonic Mouse Spinal Cord
M. Gartz
Hanson and
Lynn T.
Landmesser
Department of Neurosciences, Case Western Reserve University,
School of Medicine, Cleveland, Ohio 44106-4975
In the developing nervous system, patterned spontaneous activity
affects a variety of developmental processes. Thus, it is important to
identify the earliest time that such activity occurs and to
characterize the underlying circuitry. In isolated mouse spinal
cord-limb preparations, highly rhythmic spontaneous activity occurred
as early as embryonic day 11 (E11)-E12, when many lumbosacral motoneurons were still migrating and extending their peripheral projections. This activity required both electrical and chemical transmission, and acetylcholine, rather than glutamate, provided the
main excitatory drive. Our data are consistent with motoneurons themselves playing a critical role in generating such activity by
making excitatory connections on each other and on GABAergic interneurons via dihydro- -erythroidine hydrobromide
(DH E)-insensitive nicotinic receptors. This resulted in the
generation of local bursts. Consistent with these observations,
E12-E12.5 mouse motoneurons retrogradely labeled by HRP were observed
to have extensive axon collaterals that projected locally within the
lateral motor column and to interneuron-containing regions dorsal and
medial of the lateral motor column. Cholinergic axons, presumably from
motoneurons, were also observed in the ventral and lateral funiculi.
However, for local bursts to propagate throughout the cord, a second
DH E-sensitive cholinergic pathway that also involved glycinergic
interneurons was required. This circuit characterization should
facilitate the use of genetic mutations that alter specific
subpopulations of interneurons or cholinergic transmission to determine
how modifying different aspects of this early activity affects
subsequent development of the spinal motor circuit.
Key words:
motoneuron; interneuron; motor; cholinergic; glycinergic; GABAergic; gap junctions; development
Copyright © 2003 Society for Neuroscience 0270-6474/03/232587-14$05.00/0
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