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Free keywords:
Animals
Brain-Derived Neurotrophic Factor/pharmacology/*physiology
Calcium/metabolism
Calcium Channel Blockers/pharmacology
Calcium Channels/drug effects/physiology
Calcium Signaling/*physiology
Electrophysiology
Hippocampus/drug effects/metabolism/*physiology
In Vitro Techniques
Ion Channel Gating
Long-Term Potentiation/*physiology
Male
Neurotrophin 3/pharmacology/*physiology
Rats
Rats, Sprague-Dawley
Synaptic Transmission/physiology
Abstract:
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 physiological 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 (Ca(2+)) sources, voltage-gated Ca(2+) channels and intracellular Ca(2+) stores, we show that the potentiating effects of neurotrophins in hippocampal slices are mediated by intracellular Ca(2+) signaling. Although basal synaptic transmission between hippocampal CA3 and CA1 neurons was not affected by nifedipine or thapsigargin, both drugs significantly attenuated brain-derived neurotrophic factor or neurotrophin-3-induced synaptic enhancement. The pharmacological blockade of Ca(2+) signaling is effective only during the initial period of neurotrophin-induced potentiation. These data suggest that the minimal requirements for inducing potentiation by neurotrophins involve a transient increase in intracellular Ca(2+) concentration, via voltage-gated Ca(2+) channels and/or intracellular Ca(2+) stores.
