Embryonically expressed GABA and glutamate drive electrical activity regulating neurotransmitter specification.
Neurotransmitter signaling in the mature nervous system is well understood, but the functions of transmitters in the immature nervous system are less clear. Although transmitters released during embryogenesis regulate neuronal proliferation and migration, little is known about their role in regulating early neuronal differentiation. Here, we show that GABA and glutamate drive calcium-dependent embryonic electrical activity that regulates transmitter specification. The number of neurons expressing different transmitters changes when GABA or glutamate signaling is blocked chronically, either using morpholinos to knock down transmitter-synthetic enzymes or applying pharmacological receptor antagonists during a sensitive period of development. We find that calcium spikes are triggered by metabotropic GABA and glutamate receptors, which engage protein kinases A and C. The results reveal a novel role for embryonically expressed neurotransmitters.
Root
Cory M
CM
Neurobiology Section, Division of Biological Sciences and Center for Molecular Genetics, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, California 92093-0357, USA.
Velázquez-Ulloa
Norma A
NA
Monsalve
Gabriela C
GC
Minakova
Elena
E
Spitzer
Nicholas C
NC
D000818:Animals; D018959:CD57 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006302:Health Services Research; D007814:Larva; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010768:Phosphoserine / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018959:CD57 Antigens; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009025:Morpholines; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D050496:Vesicular Glutamate Transport Proteins; C120877:methylserine phosphate; D010768:Phosphoserine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D002118:Calcium