Synaptic input as a directional cue for migrating interneuron precursors

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 -