Calcium-calmodulin signalling pathway up-regulates glutamatergic synaptic function in non-pyramidal, fast spiking rat hippocampal CA1 neurons

1. The role of Ca2+-calmodulin (CaM) signalling cascades in modulating glutamatergic synaptic transmission on CA1 non-pyramidal fast-spiking neurons was investigated using whole-cell recording and perfusion in rat hippocampal slices. 2. Paired stimuli (PS), consisting of postsynaptic depolarization to 0 mV and presynaptic stimulation at 1 Hz for 30 s, enhanced excitatory postsynaptic currents (EPSCs) on non-pyramidal neurons in the stratum pyramidale (SP). The potentiation was reduced by the extracellular application of D-amino-5-phosphonovaleric acid (DAP-5, 40 muM), and blocked by the postsynaptic perfusion of 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA, 10 mM), a CaM-binding peptide (100 muM) or CaMKII (281-301) (an autoinhibitory peptide of CaM-dependent protein kinases, 100 muM). 3. The application of adenophostin, an agonist of inositol trisphosphate receptors (IP(3)Rs) that evokes Ca2+ release, into SP non-pyramidal neurons via the patch pipette (1 muM) enhanced EPSCs and occluded PS-induced synaptic potentiation. The co-application of BAPTA (10 mM) with adenophostin blocked synaptic potentiation. In addition, Ca2+-CaM (40:10 muM) induced synaptic potentiation, which occluded PS-induced potentiation and was attenuated by introducing CaMKII(281-301) (100 muM). EPSCs were sensitive to an antagonist of alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR). 4. Application of Ca2+-CaM into SP non-pyramidal neurons induced the emergence of AMPAR-mediated EPSCs that were not evoked by low stimulus intensity before perfusion. Ca2+-CaM also increased the amplitude and frequency of spontaneous EPSCs. A scavenger of nitric oxide, carhoxy-PTIO (30 muM in slice-perfusion solution), did not affect these increases in sEPSCs. 5. The magnitude of PS-, adenophostin- or Ca2+-CaM-induced synaptic potentiation in SP nonpyramidal neurons increased during postnatal development. 6. These results indicate that Ca2+-CaM signalling pathways in CA1 SP non-pyramidal neurons up-regulate glutamatergic synaptic transmission probably through the conversion of inactive-to-active synapses.