Irregular Breathing in Mice following Genetic Ablation of V2a Neurons.
Neural networks called central pattern generators (CPGs) generate repetitive motor behaviors such as locomotion and breathing. Glutamatergic neurons are required for the generation and inhibitory neurons for the patterning of the motor activity associated with repetitive motor behaviors. In the mouse, glutamatergic V2a neurons coordinate the activity of left and right leg CPGs in the spinal cord enabling mice to generate an alternating gait. Here, we investigate the role of V2a neurons in the neural control of breathing, an essential repetitive motor behavior. We find that, following the ablation of V2a neurons, newborn mice breathe at a lower frequency. Recordings of respiratory activity in brainstem-spinal cord and respiratory slice preparations demonstrate that mice lacking V2a neurons are deficient in central respiratory rhythm generation. The absence of V2a neurons in the respiratory slice preparation can be compensated for by bath application of neurochemicals known to accelerate the breathing rhythm. In this slice preparation, V2a neurons exhibit a tonic firing pattern. The existence of direct connections between V2a neurons in the medial reticular formation and neurons of the pre-Bötzinger complex indicates that V2a neurons play a direct role in the function of the respiratory CPG in newborn mice. Thus, neurons of the embryonic V2a lineage appear to have been recruited to neural networks that control breathing and locomotion, two prominent CPG-driven, repetitive motor behaviors.
Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
Steven A
SA
Crone
Jean-Charles
JC
Viemari
Steven
S
Droho
Ana
A
Mrejeru
Jan-Marino
JM
Ramirez
Kamal
K
Sharma
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D003627:Data Interpretation, Statistical; D055724:Electrophysiological Phenomena; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D009415:Nerve Net / Q000502:physiology; D010993:Plethysmography, Whole Body; D012119:Respiration / Q000235:genetics*; D012249:Rhombencephalon / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; C088975:Vsx2 protein, mouse