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The Journal of Neuroscience, August 15, 1999, 19(16):7025-7036
Long-Term Enhancement of Central Synaptic Transmission by Chronic
Brain-Derived Neurotrophic Factor Treatment
Nina Tang
Sherwood and
Donald C.
Lo
Department of Neurobiology, Duke University Medical Center, Durham,
North Carolina 27710
Acute effects of neurotrophins on synaptic plasticity have recently
received much attention, but the roles of these factors in regulating
long-lasting changes in synaptic function remain unclear. To address
this issue we studied the long-term (days to weeks) and short-term
(minutes to hours) effects of brain-derived neurotrophic factor (BDNF)
on excitatory synaptic transmission in autaptic cultures of hippocampal
CA1 neurons. We found that BDNF induced long-term enhancement of the
strength of non-NMDA receptor-mediated glutamatergic transmission. This
upregulation of EPSC amplitude occurred via an increase in the
size of unitary synaptic currents, with no significant contribution
from other aspects of neuronal electrical and synaptic function
including cell size, voltage-gated sodium and potassium current levels, the number and size of synaptic contacts, and the frequency of spontaneous neurotransmitter release. Chronic BDNF treatment also decreased the degree of synaptic depression measured in response to
paired stimuli. Thus, BDNF induced long-term synaptic enhancement of
both basal and use-dependent synaptic transmission via specific changes
to the synapse rather than through generalized potentiation of neuronal
growth and differentiation. Finally, we showed that the long-term
effects of BDNF are functionally and mechanistically distinct from its
acute effects on synaptic transmission, suggesting that, in
vivo, BDNF activation of Trk receptors can have different functional effects depending on the time course of its action.
Key words:
neurotrophins; BDNF; Trk receptors; TrkB; hippocampal
neurons; synaptic plasticity; excitatory synaptic transmission; autapses; microcultures
Copyright © 1999 Society for Neuroscience 0270-6474/99/19167025-12$05.00/0
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