Uncoupling of EphA/ephrinA signaling and spontaneous activity in neural circuit wiring.
Classic studies have proposed that genetically encoded programs and spontaneous activity play complementary but independent roles in the development of neural circuits. Recent evidence, however, suggests that these two mechanisms could interact extensively, with spontaneous activity affecting the expression and function of guidance molecules at early developmental stages. Here, using the developing chick spinal cord and the mouse visual system to ectopically express the inwardly rectifying potassium channel Kir2.1 in individual embryonic neurons, we demonstrate that cell-intrinsic blockade of spontaneous activity in vivo does not affect neuronal identity specification, axon pathfinding, or EphA/ephrinA signaling during the development of topographic maps. However, intrinsic spontaneous activity is critical for axon branching and pruning once axonal growth cones reach their correct topographic position in the target tissues. Our experiments argue for the dissociation of spontaneous activity from hard-wired developmental programs in early phases of neural circuit formation.
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Isabel
I
Benjumeda
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Augusto
A
Escalante
Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.
Chris
C
Law
Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.|McGill University Integrated Program in Neuroscience, Montréal, Québec H3A 2B4.
Daniel
D
Morales
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Geraud
G
Chauvin
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Gerald
G
Muça
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Yaiza
Y
Coca
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Joaquín
J
Márquez
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Guillermina
G
López-Bendito
Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.|McGill University Integrated Program in Neuroscience, Montréal, Québec H3A 2B4.|Departments of Anatomy and Cell Biology, and Biology, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 2B2.|Faculté de Médecine, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
Artur
A
Kania
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Luis
L
Martínez
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, Campus San Juan de Alicante, 03550 Alicante, Spain.
Eloísa
E
Herrera
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002642:Chick Embryo; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009415:Nerve Net / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D036081:Receptors, Eph Family