Synaptic input as a directional cue for migrating interneuron precursors
Standard
Synaptic input as a directional cue for migrating interneuron precursors. / Wefers, Annika K; Haberlandt, Christian; Tekin, Nuriye B; Fedorov, Dmitry A; Timmermann, Aline; van der Want, Johannes J L; Chaudhry, Farrukh A; Steinhäuser, Christian; Schilling, Karl; Jabs, Ronald.
in: DEVELOPMENT, Jahrgang 144, Nr. 22, 15.11.2017, S. 4125-4136.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Synaptic input as a directional cue for migrating interneuron precursors
AU - Wefers, Annika K
AU - Haberlandt, Christian
AU - Tekin, Nuriye B
AU - Fedorov, Dmitry A
AU - Timmermann, Aline
AU - van der Want, Johannes J L
AU - Chaudhry, Farrukh A
AU - Steinhäuser, Christian
AU - Schilling, Karl
AU - Jabs, Ronald
N1 - © 2017. Published by The Company of Biologists Ltd.
PY - 2017/11/15
Y1 - 2017/11/15
N2 - During CNS development, interneuron precursors have to migrate extensively before they integrate in specific microcircuits. Known regulators of neuronal motility include classical neurotransmitters, yet the mechanisms that assure interneuron dispersal and interneuron/projection neuron matching during histogenesis remain largely elusive. We combined time-lapse video microscopy and electrophysiological analysis of the nascent cerebellum of transgenic Pax2-EGFP mice to address this issue. We found that cerebellar interneuronal precursors regularly show spontaneous postsynaptic currents, indicative of synaptic innervation, well before settling in the molecular layer. In keeping with the sensitivity of these cells to neurotransmitters, ablation of synaptic communication by blocking vesicular release in acute slices of developing cerebella slows migration. Significantly, abrogation of exocytosis primarily impedes the directional persistence of migratory interneuronal precursors. These results establish an unprecedented function of the early synaptic innervation of migrating neuronal precursors and demonstrate a role for synapses in the regulation of migration and pathfinding.
AB - During CNS development, interneuron precursors have to migrate extensively before they integrate in specific microcircuits. Known regulators of neuronal motility include classical neurotransmitters, yet the mechanisms that assure interneuron dispersal and interneuron/projection neuron matching during histogenesis remain largely elusive. We combined time-lapse video microscopy and electrophysiological analysis of the nascent cerebellum of transgenic Pax2-EGFP mice to address this issue. We found that cerebellar interneuronal precursors regularly show spontaneous postsynaptic currents, indicative of synaptic innervation, well before settling in the molecular layer. In keeping with the sensitivity of these cells to neurotransmitters, ablation of synaptic communication by blocking vesicular release in acute slices of developing cerebella slows migration. Significantly, abrogation of exocytosis primarily impedes the directional persistence of migratory interneuronal precursors. These results establish an unprecedented function of the early synaptic innervation of migrating neuronal precursors and demonstrate a role for synapses in the regulation of migration and pathfinding.
KW - Animals
KW - Cell Movement
KW - Cell Shape
KW - Cerebellum/cytology
KW - Electrophysiological Phenomena
KW - Female
KW - Glutamates/metabolism
KW - Interneurons/cytology
KW - Male
KW - Mice, Inbred C57BL
KW - Models, Biological
KW - Neural Stem Cells/cytology
KW - PAX2 Transcription Factor/metabolism
KW - Synapses/metabolism
KW - gamma-Aminobutyric Acid/metabolism
U2 - 10.1242/dev.154096
DO - 10.1242/dev.154096
M3 - SCORING: Journal article
C2 - 29061636
VL - 144
SP - 4125
EP - 4136
JO - DEVELOPMENT
JF - DEVELOPMENT
SN - 0950-1991
IS - 22
ER -