Intracellular Ca2+ signaling is required for neurotrophin-induced potentiation in the adult rat hippocampus

Recent studies have demonstrated the importance of neurotrophin function in adult synaptic plasticity. In an effort to characterize the intracellular signaling pathways that couple Trk receptor activation to the final physiol ogical effects of neurotrophins, we have examined the role of intracellular calcium rises in neurotrophin-induced synaptic enhancement in hippocampal slices, Using pharmacological blockers to two different calcium ion (Ca2+) sources, voltage-gated Ca2+ channels and intracellular Ca2+ stores, we show that the potentiating effects of neurotrophins in hippocampal slices are m ediated by intracellular Ca2+ signaling. Although basal synaptic transmissi on between hippocampal CA3 and CA1 neurons was not affected by nifedipine o r thapsigargin, both drugs significantly attenuated brain-derived neurotrop hic factor or neurotrophin-3-induced synaptic enhancement. The pharmacologi cal blockade of Ca2+ signaling is effective only during the initial period of neurotrophin-induced potentiation. These data suggest that the minimal r equirements for inducing potentiation by neurotrophins involve a transient increase in intracellular Ca2+ concentration, via voltage-gated Ca2+ channe ls and/or intracellular Ca2+ stores. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.