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 glut amatergic synaptic transmission on CA1 non-pyramidal fast-spiking neurons w as investigated using whole-cell recording and perfusion in rat hippocampal slices. 2. Paired stimuli (PS), consisting of postsynaptic depolarization to 0 mV a nd presynaptic stimulation at 1 Hz for 30 s, enhanced excitatory postsynapt ic 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 pe rfusion 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 autoinhib itory peptide of CaM-dependent protein kinases, 100 muM). 3. The application of adenophostin, an agonist of inositol trisphosphate re ceptors (IP(3)Rs) that evokes Ca2+ release, into SP non-pyramidal neurons v ia the patch pipette (1 muM) enhanced EPSCs and occluded PS-induced synapti c potentiation. The co-application of BAPTA (10 mM) with adenophostin block ed synaptic potentiation. In addition, Ca2+-CaM (40:10 muM) induced synapti c potentiation, which occluded PS-induced potentiation and was attenuated b y introducing CaMKII(281-301) (100 muM). EPSCs were sensitive to an antagon ist 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 emerge nce of AMPAR-mediated EPSCs that were not evoked by low stimulus intensity before perfusion. Ca2+-CaM also increased the amplitude and frequency of sp ontaneous 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 potenti ation in SP nonpyramidal neurons increased during postnatal development. 6. These results indicate that Ca2+-CaM signalling pathways in CA1 SP non-pyr amidal neurons up-regulate glutamatergic synaptic transmission probably thr ough the conversion of inactive-to-active synapses.