Neurotrophin 3 potentiates neuronal activity and inhibits gamma-aminobutyratergic synaptic transmission in cortical neurons.
Neurotrophins have traditionally been regarded as slowly acting signals essential for neuronal survival and differentiation. However, brain-derived neurotrophic factor and neurotrophin 3 (NT-3) have recently been reported to exert an acute potentiation of synaptic activity at the amphibian neuromuscular junction. Little is known about the role of neurotrophins on functional synapses in the central nervous system. Here we show that NT-3 rapidly increased the frequency of spontaneous action potentials, and it synchronized excitatory synaptic activities in developing cortical neurons. Moreover, the inhibitory synaptic transmission mediated by gamma-aminobutyric acid (GABA) subtype A receptors was found to be reduced by NT-3. Thus, the excitatory effects of NT-3 on spontaneous action potentials were attributable to a reduction of GABAergic transmission. Our findings, together with previous reports of rapid regulation of central nervous system neurotrophin expression by neuronal activity and of the role of GABAergic transmission in cortical plasticity, suggest a mechanism for modulation of synaptic transmission and activity-dependent synaptic modulation in cortical neurons.
Kim
H G
HG
Roche Institute of Molecular Biology, Nutley, NJ 07110.
Wang
T
T
Olafsson
P
P
Lu
B
B
D000663:Amphibians; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005071:Evoked Potentials / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D006801:Humans; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D020933:Neurotrophin 3; D016133:Polymerase Chain Reaction; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA / Q000096:biosynthesis; D020812:Receptor, trkC; D011963:Receptors, GABA-A / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D017931:DNA Primers; D058787:GABA-A Receptor Antagonists; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020801:Receptor, Ciliary Neurotrophic Factor; D011963:Receptors, GABA-A; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC