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The Journal of Neuroscience, May 1, 2000, 20(9):3221-3232
Brain-Derived Neurotrophic Factor Differentially Regulates
Excitatory and Inhibitory Synaptic Transmission in Hippocampal
Cultures
M. McLean
Bolton,
Andrew J.
Pittman, and
Donald C.
Lo
Department of Neurobiology, Duke University Medical Center, Durham,
North Carolina 27710
Brain-derived neurotrophic factor (BDNF) has been postulated to be
a key signaling molecule in regulating synaptic strength and overall
circuit activity. In this context, we have found that BDNF dramatically
increases the frequency of spontaneously initiated action potentials in
hippocampal neurons in dissociated culture. Using analysis of unitary
synaptic transmission and immunocytochemical methods, we determined
that chronic treatment with BDNF potentiates both excitatory and
inhibitory transmission, but that it does so via different mechanisms.
BDNF strengthens excitation primarily by augmenting the amplitude of
AMPA receptor-mediated miniature EPSCs (mEPSCs) but
enhances inhibition by increasing the frequency of mIPSC and increasing
the size of GABAergic synaptic terminals. In contrast to observations
in other systems, BDNF-mediated increases in AMPA-receptor mediated
mEPSC amplitudes did not require activity, because blocking action
potentials with tetrodotoxin for the entire duration of BDNF
treatment had no effect on the magnitude of this enhancement. These
forms of synaptic regulations appear to be a selective action of BDNF
because intrinsic excitability, synapse number, and neuronal survival
are not affected in these cultures. Thus, although BDNF induces a net
increase in overall circuit activity, this results from potentiation of
both excitatory and inhibitory synaptic drive through distinct and
selective physiological mechanisms.
Key words:
neurotrophins; BDNF; hippocampal neurons; synaptic
plasticity; excitatory synaptic transmission; inhibitory synaptic
transmission; AMPA receptors; NMDA receptors
Copyright © 2000 Society for Neuroscience 0270-6474/00/2093221-12$05.00/0
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