Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination.
During late embryonic and early postnatal life, neuromuscular junctions undergo synapse elimination that is modulated by patterns of motor neuron activity. Here, we test the hypothesis that reduced spinal neuron gap junctional coupling decreases temporally correlated motor neuron activity that, in turn, modulates neuromuscular synapse elimination, by using mutant mice lacking connexin 40 (Cx40), a developmentally regulated gap junction protein expressed in motor and other spinal neurons. In Cx40-/- mice, electrical coupling among lumbar motor neurons, measured by whole-cell recordings, was reduced, and single motor unit recordings in awake, behaving neonates showed that temporally correlated motor neuron activity was also reduced. Immunostaining and intracellular recording showed that the neuromuscular synapse elimination was accelerated in muscles from Cx40-/- mice compared with WT littermates. Our work shows that gap junctional coupling modulates neuronal activity patterns that, in turn, mediate synaptic competition, a process that shapes synaptic circuitry in the developing brain.
Personius
Kirkwood E
KE
Department of Rehabilitation Science, School of Public Health and Health Professions, University at Buffalo, the State University of New York, Buffalo, NY 14214-3079, USA.
Chang
Qiang
Q
Mentis
George Z
GZ
O'Donovan
Michael J
MJ
Balice-Gordon
Rita J
RJ
D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017630:Connexins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D009469:Neuromuscular Junction / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D011930:Reaction Time / Q000235:genetics / Q000502:physiology; D000097003:Gap Junction alpha-5 Protein
D017630:Connexins; D000097003:Gap Junction alpha-5 Protein