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The Journal of Neuroscience, September 15, 1998, 18(18):7256-7271
Neurotrophins Induce Formation of Functional Excitatory and
Inhibitory Synapses between Cultured Hippocampal Neurons
Carlos
Vicario-Abejón1,
Carlos
Collin1,
Ronald D. G.
McKay1, and
Menahem
Segal2
1 Laboratory of Molecular Biology, National Institute
of Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, Maryland 20892-4092, and 2 Department of
Neurobiology, The Weizmann Institute, Rehovot 76100, Israel
Cell cultures were used to analyze the role of brain-derived
neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the development of synaptic transmission. Neurons obtained from embryonic day 18 (E18)
rat hippocampus and cultured for 2 weeks exhibited extensive spontaneous synaptic activity. By comparison, neurons obtained from E16
hippocampus expressed very low levels of spontaneous or evoked synaptic
activity. Neurotrophin treatment produced a sevenfold increase in the
number of functional synaptic connections in the E16 cultures. BDNF
induced formation of both excitatory and inhibitory synapses, whereas
NT-3 induced formation of only excitatory synapses. These effects were
independent of serum or the age of the glia bed used for the culture.
They were not accompanied by significant changes in
synaptic-vesicle-associated proteins or glutamate receptors. Treatment
of the cultures with the neurotrophins for 3 d was sufficient to
establish the maximal level of functional synapses. During this period,
neurotrophins did not affect the viability or the morphology of the
excitatory neurons, although they did produce an increase in the number
and length of dendrites of the GABAergic neurons. Remarkably, only BDNF
caused an increase in the number of axonal branches and in the total
length of the axons of the GABAergic neurons. These results support a
unique and differential role for neurotrophins in the formation of
excitatory and inhibitory synapses in the developing hippocampus.
Key words:
synapses; hippocampus; culture; BDNF; NT-3; GABA
Copyright © 1998 Society for Neuroscience 0270-6474/98/18187256-16$05.00/0
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