The mossy fiber-CA3 pyramidal neuron synapse is a main component of the hip
pocampal trisynaptic circuitry. Recent studies, however, suggested that inh
ibitory interneurons are the major targets of the mossy fiber system. To st
udy the regulation of mossy fiber-interneuron excitation, we examined unita
ry and compound excitatory postsynaptic currents in dentate gyrus basket ce
lls, evoked by paired recording between granule and basket cells or extrace
llular stimulation of mossy fiber collaterals. The application of an associ
ative high-frequency stimulation paradigm induced posttetanic potentiation
(PTP) followed by homosynaptic longterm potentiation (LTP). Analysis of num
bers of failures, coefficient of variation, and paired-pulse modulation ind
icated that both PTP and LTP were expressed presynaptically. The Ca2+ chela
tor 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) did no
t affect PTP or LTP at a concentration of 10 mM but attenuated LTP at a con
centration of 30 mM. Both forskolin, an adenylyl cyclase activator, and pho
rbolester diacetate, a protein kinase C stimulator, lead to along-lasting i
ncrease in excitatory postsynaptic current amplitude. H-89, a protein kinas
e A inhibitor, and bisindolylmaleimide, a protein kinase C antagonist, redu
ced PTP, whereas only bisindolylmaleimide reduced LTP. These results may su
ggest a differential contribution of protein kinase A and C pathways to mos
sy fiber-interneuron plasticity. Interneuron PTP and LTP may provide mechan
isms to maintain the balance between synaptic excitation of interneurons an
d that of principal neurons in the dentate gyrus-CA3 network.