Long-Term Enhancement of Central Synaptic Transmission by Chronic Brain-Derived Neurotrophic Factor Treatment

Abstract

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.